Human Genes Group 8 Flashcards
1
Q
CCN1
A
CCN family member 1 (Cellular communication network factor 1) (Cysteine-rich angiogenic inducer 61) (Insulin-like growth factor-binding protein 10) (IBP-10) (IGF-binding protein 10) (IGFBP-10) (Protein CYR61) (Protein GIG1) O00622 FUNCTION: Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CCN1-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3. SUBCELLULAR LOCATION: Secreted.
2
Q
CCNB2
A
G2/mitotic-specific cyclin-B2 O95067 FUNCTION: Essential for the control of the cell cycle at the G2/M (mitosis) transition.
3
Q
MLLT11
A
Protein AF1q Q13015 FUNCTION: Cofactor for the transcription factor TCF7 . Involved in regulation of lymphoid development by driving multipotent hematopoietic progenitor cells towards a T cell fate .
4
Q
CCSER2
A
Serine-rich coiled-coil domain-containing protein 2 (Coiled-coil serine-rich protein 2) (Protein GCAP14 homolog) Q9H7U1 FUNCTION: Microtubule-binding protein which might play a role in microtubule bundling.
5
Q
CCS
A
Copper chaperone for superoxide dismutase (Superoxide dismutase copper chaperone) O14618 FUNCTION: Delivers copper to copper zinc superoxide dismutase (SOD1). SUBCELLULAR LOCATION: Cytoplasm .
6
Q
CCNYL2
A
Cyclin-Y-like protein 2 Q5T2Q4
7
Q
CDCA7
A
Cell division cycle-associated protein 7 (Protein JPO1) Q9BWT1 FUNCTION: Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly nuclear with some expression also seen in the cytoplasm. Predominantly cytoplasmic when phosphorylated at Thr-163.
8
Q
CDCA3
A
Cell division cycle-associated protein 3 (Gene-rich cluster protein C8) (Trigger of mitotic entry protein 1) (TOME-1) Q99618 FUNCTION: F-box-like protein which is required for entry into mitosis. Acts by participating in E3 ligase complexes that mediate the ubiquitination and degradation of WEE1 kinase at G2/M phase (By similarity).
9
Q
BMP10
A
Bone morphogenetic protein 10 (BMP-10) O95393 FUNCTION: Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.
10
Q
ARHGEF28
A
Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor) Q8N1W1 FUNCTION: Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Functions also in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity).
11
Q
BBX
A
HMG box transcription factor BBX (Bobby sox homolog) (HMG box-containing protein 2) Q8WY36 FUNCTION: Transcription factor that is necessary for cell cycle progression from G1 to S phase.
12
Q
C13orf46
A
Uncharacterized protein C13orf46 A0A1B0GUA9
13
Q
CHMP4B
A
Charged multivesicular body protein 4b (Chromatin-modifying protein 4b) (CHMP4b) (SNF7 homolog associated with Alix 1) (SNF7-2) (hSnf7-2) (Vacuolar protein sorting-associated protein 32-2) (Vps32-2) (hVps32-2) Q9H444 FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (, ). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis . Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase . Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan .
14
Q
MPIG6B
A
Megakaryocyte and platelet inhibitory receptor G6b (Protein G6b) O95866 FUNCTION: Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (, , ). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide . This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling . Appears to operate in a calcium-independent manner .
15
Q
DENND5A
A
DENN domain-containing protein 5A (Rab6-interacting protein 1) (Rab6IP1) Q6IQ26 FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity).
16
Q
FILIP1
A
Filamin-A-interacting protein 1 (FILIP) Q7Z7B0 FUNCTION: By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone. May be able to induce the degradation of filamin-A.
17
Q
FOXJ2
A
Forkhead box protein J2 (Fork head homologous X) Q9P0K8 FUNCTION: Transcriptional activator. Able to bind to two different type of DNA binding sites. Isoform FOXJ2.L behaves as a more potent transactivator than FOXJ2. SUBCELLULAR LOCATION: Nucleus.
18
Q
FBXL2
A
F-box/LRR-repeat protein 2 (F-box and leucine-rich repeat protein 2) (F-box protein FBL2/FBL3) Q9UKC9 FUNCTION: Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (, ). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy . PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity).
19
Q
FCRL2
A
Fc receptor-like protein 2 (FcR-like protein 2) (FcRL2) (Fc receptor homolog 2) (FcRH2) (IFGP family protein 4) (Immunoglobulin receptor translocation-associated protein 4) (SH2 domain-containing phosphatase anchor protein 1) (CD antigen CD307b) Q96LA5 FUNCTION: May have an regulatory role in normal and neoplastic B cell development.
20
Q
FRAT2
A
GSK-3-binding protein FRAT2 (Frequently rearranged in advanced T-cell lymphomas 2) (FRAT-2) O75474 FUNCTION: Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3.
21
Q
FCRL5
A
Fc receptor-like protein 5 (FcR-like protein 5) (FcRL5) (BXMAS1) (Fc receptor homolog 5) (FcRH5) (Immune receptor translocation-associated protein 2) (CD antigen CD307e) Q96RD9 FUNCTION: May be involved in B-cell development and differentiation in peripheral lymphoid organs and may be useful markers of B-cell stages. May have an immunoregulatory role in marginal zone B-cells.
22
Q
MFGE8
A
Lactadherin (Breast epithelial antigen BA46) (HMFG) (MFGM) (Milk fat globule-EGF factor 8) (MFG-E8) (SED1) [Cleaved into: Lactadherin short form; Medin] Q08431 FUNCTION: Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization (By similarity). Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction.
23
Q
EIF4E
A
Eukaryotic translation initiation factor 4E (eIF-4E) (eIF4E) (eIF-4F 25 kDa subunit) (mRNA cap-binding protein) P06730 FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.
24
Q
LIMS1
A
LIM and senescent cell antigen-like-containing domain protein 1 (Particularly interesting new Cys-His protein 1) (PINCH-1) (Renal carcinoma antigen NY-REN-48) P48059 FUNCTION: Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Involved in the regulation of cell survival, cell proliferation and cell differentiation. SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side.
25
IGFL2
Insulin growth factor-like family member 2 Q6UWQ7 FUNCTION: Potential ligand of the IGFLR1 cell membrane receptor.
26
GSX2
GS homeobox 2 (Genetic-screened homeobox 2) (Homeobox protein GSH-2) Q9BZM3 FUNCTION: During telencephalic development, causes ventralization of pallial progenitors and, depending on the developmental stage, specifies different neuronal fates. At early stages, necessary and sufficient to correctly specify the ventral lateral ganglionic eminence (LGE) and its major derivatives, the striatal projection neurons. At later stages, may specify LGE progenitors toward dorsal LGE fates, including olfactory bulb interneurons (By similarity). Transcription factor that binds 5'-CNAATTAG-3' DNA sequence.
27
INPP4B
Inositol polyphosphate 4-phosphatase type II (Type II inositol 3,4-bisphosphate 4-phosphatase) (EC 3.3.66) O15327 FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-trisphosphate (, ). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles . The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (, ).
28
IMPA1
Inositol monophosphatase 1 (IMP 1) (IMPase 1) (EC 3.3.25) (D-galactose 1-phosphate phosphatase) (EC 3.3.94) (Inositol-1(or 4)-monophosphatase 1) (Lithium-sensitive myo-inositol monophosphatase A1) P29218 FUNCTION: Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.
29
IGLV5-48
Probable non-functional immunoglobulin lambda variable 5-48 A0A075B6I7 FUNCTION: Probable non-functional open reading frame (ORF) of V region of the variable domain of immunoglobulin light chains . Non-functional ORF generally cannot participate in the synthesis of a productive immunoglobulin chain due to altered V-(D)-J or switch recombination and/or splicing site (at mRNA level) and/or conserved amino acid change (protein level) . Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (, ). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (, ).
30
ITPRIPL1
Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1 Q6GPH6 SUBCELLULAR LOCATION: Membrane .
31
IPPK
Inositol-pentakisphosphate 2-kinase (EC 2.1.158) (IPK1 homolog) (Inositol-1,3,4,5,6-pentakisphosphate 2-kinase) (Ins(1,3,4,5,6)P5 2-kinase) (InsP5 2-kinase) Q9H8X2 FUNCTION: Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, non-homologous end-joining, endocytosis, ion channel regulation. It also protects cells from TNF-alpha-induced apoptosis.
32
NLRC4
NLR family CARD domain-containing protein 4 (CARD, LRR, and NACHT-containing protein) (Clan protein) (Caspase recruitment domain-containing protein 12) (Ice protease-activating factor) (Ipaf) Q9NPP4 FUNCTION: Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis . The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity). Note=Cytoplasmic filaments.
33
MYH13
Myosin-13 (Myosin heavy chain 13) (Myosin heavy chain, skeletal muscle, extraocular) (MyHC-EO) (Myosin heavy chain, skeletal muscle, laryngeal) (MyHC-IIL) (Superfast myosin) Q9UKX3 FUNCTION: Fast twitching myosin mediating the high-velocity and low-tension contractions of specific striated muscles. SUBCELLULAR LOCATION: Cytoplasm, myofibril. Note=Thick filaments of the myofibrils.
34
MYH9
Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) P35579 FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10.
35
NT5DC4
5'-nucleotidase domain-containing protein 4 Q86YG4
36
PTPN3
Tyrosine-protein phosphatase non-receptor type 3 (EC 3.3.48) (Protein-tyrosine phosphatase H1) (PTP-H1) P26045 FUNCTION: May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton.
37
TMEM258
Transmembrane protein 258 (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit TMEM258) (Oligosaccharyl transferase subunit TMEM258) P61165 FUNCTION: Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (, ). Involved in ER homeostasis in the colonic epithelium (By similarity).
38
TMEM262
Transmembrane protein 262 E9PQX1 SUBCELLULAR LOCATION: Membrane .
39
TENT5C
Terminal nucleotidyltransferase 5C (EC 2.7.19) (Non-canonical poly(A) polymerase FAM46C) Q5VWP2 FUNCTION: Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.
40
TENT5D
Terminal nucleotidyltransferase 5D (EC 2.7.19) (Non-canonical poly(A) polymerase FAM46D) Q8NEK8 FUNCTION: Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase.
41
TMEM269
Transmembrane protein 269 A0A1B0GVZ9 SUBCELLULAR LOCATION: Membrane .
42
TMEM271
Transmembrane protein 271 A0A286YF58 SUBCELLULAR LOCATION: Membrane .
43
TMEM273
Transmembrane protein 273 Q5T292 SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
44
SNRPN
Small nuclear ribonucleoprotein-associated protein N (snRNP-N) (Sm protein D) (Sm-D) (Sm protein N) (Sm-N) (SmN) (Tissue-specific-splicing protein) P63162 FUNCTION: May be involved in tissue-specific alternative RNA processing events. SUBCELLULAR LOCATION: Nucleus.
45
TEX12
Testis-expressed protein 12 Q9BXU0
46
TMEM35B
Transmembrane protein 35B (ZMYM6 neighbor protein) Q8NCS4 SUBCELLULAR LOCATION: Membrane .
47
TMEM38A
Trimeric intracellular cation channel type A (TRIC-A) (TRICA) (Transmembrane protein 38A) Q9H6F2 FUNCTION: Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.
48
TEX19
Testis-expressed protein 19 Q8NA77 FUNCTION: Required during spermatogenesis and placenta development, participating in the repression of retrotransposable elements and prevent their mobilization. Collaborates with the Piwi-interacting RNA (piRNA) pathway, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins. Interacts with Piwi proteins and directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Also during spermatogenesis, promotes, with UBR2, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Interacts with LINE-1 retrotransposon encoded LIRE1, stimulates LIRE1 polyubiquitination, mediated by UBR2, and degradation, inhibiting LINE-1 retrotransposon mobilization .
49
TEX22
Testis-expressed protein 22 C9J3V5 SUBCELLULAR LOCATION: Cytoplasm .
50
TEX28; TEX28P1; TEX28P2
Testis-specific protein TEX28 O15482 SUBCELLULAR LOCATION: Membrane .
51
TEX29
Testis-expressed protein 29 Q8N6K0 SUBCELLULAR LOCATION: Membrane .
52
TMEM39A
Transmembrane protein 39A Q9NV64 SUBCELLULAR LOCATION: Membrane .
53
TEX2
Testis-expressed protein 2 (Transmembrane protein 96) Q8IWB9 SUBCELLULAR LOCATION: Membrane .
54
TOMM40L
Mitochondrial import receptor subunit TOM40B (Protein TOMM40-like) Q969M1 FUNCTION: Potential channel-forming protein implicated in import of protein precursors into mitochondria.
55
TEX43
Testis-expressed protein 43 Q6ZNM6
56
TEX54
Testis-expressed protein 54 A0A1B0GVG6
57
TEX9
Testis-expressed protein 9 Q8N6V9
58
TM6SF1
Transmembrane 6 superfamily member 1 Q9BZW5 FUNCTION: May function as sterol isomerase.
59
TM7SF3
Transmembrane 7 superfamily member 3 (Seven span transmembrane protein) Q9NS93 FUNCTION: Involved in the inhibition of cytokine-induced death of pancreatic beta cells. Involved in the promotion of insulin secretion from pancreatic beta cells . Is a downstream transcriptional target of p53/TP53, and acts as a pro-survival homeostatic factor that attenuates the development of cellular stress. Maintains protein homeostasis and promotes cell survival through attenuation of endoplasmic reticulum (ER) stress and the subsequent induction of unfolded protein response (UPR) .
60
TMEM86B
Lysoplasmalogenase (EC 3.2.2) (Transmembrane protein 86B) Q8N661 FUNCTION: Enzyme catalyzing the degradation of lysoplasmalogen. Lysoplasmalogens are formed by the hydrolysis of the abundant membrane glycerophospholipids plasmalogens. May control the respective levels of plasmalogens and lysoplasmalogens in cells and modulate cell membrane properties.
61
RSPH9
Radial spoke head protein 9 homolog Q9H1X1 FUNCTION: Probable component of the axonemal radial spoke head. Radial spokes are regularly spaced along cilia, sperm and flagella axonemes. They consist of a thin stalk, which is attached to a subfiber of the outer doublet microtubule, and a bulbous head, which is attached to the stalk and appears to interact with the projections from the central pair of microtubules.
62
NR5A1
Steroidogenic factor 1 (SF-1) (STF-1) (hSF-1) (Adrenal 4-binding protein) (Fushi tarazu factor homolog 1) (Nuclear receptor subfamily 5 group A member 1) (Steroid hormone receptor Ad4BP) Q13285 FUNCTION: Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues . Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1 . The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
63
GTF2B
Transcription initiation factor IIB (EC 2.1.48) (General transcription factor TFIIB) (S300-II) Q00403 FUNCTION: General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). Involved in the pre-initiation complex (PIC) formation and Pol II recruitment at promoter DNA (, , , , , , , , , , , , ). Together with the TATA box-bound TBP forms the core initiation complex and provides a bridge between TBP and the Pol II-TFIIF complex (, , , , ). Released from the PIC early following the onset of transcription during the initiation and elongation transition and reassociates with TBP during the next transcription cycle . Associates with chromatin to core promoter-specific regions (, ). Binds to two distinct DNA core promoter consensus sequence elements in a TBP-independent manner; these IIB-recognition elements (BREs) are localized immediately upstream (BREu), 5'-[GC][GC][GA]CGCC-3', and downstream (BREd), 5'-[GA]T[TGA][TG][GT][TG][TG]-3', of the TATA box element (, , , ). Modulates transcription start site selection . Exhibits also autoacetyltransferase activity that contributes to the activated transcription .
64
TM9SF4
Transmembrane 9 superfamily member 4 (Tumor cannibalism associated protein 1) Q92544 FUNCTION: Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface . Regulates the assembly and activity of V-ATPase in colon cancer cells via its interaction with V-type proton ATPase subunit H (ATP6V1H) and contributes to V-ATPase-mediated pH alterations in cancer cells which play an important role in drug resistance and invasiveness of colon cancer cells . Plays an important role in an atypical phagocytic activity of metastatic melanoma cells called cannibalism and is involved in the pH regulation of the intracellular vesicles in tumor cells .
65
RSPO3
R-spondin-3 (Protein with TSP type-1 repeat) (hPWTSR) (Roof plate-specific spondin-3) (hRspo3) (Thrombospondin type-1 domain-containing protein 2) Q9BXY4 FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (, , ). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity) (, , ). Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 .
66
TMC2
Transmembrane channel-like protein 2 (Transmembrane cochlear-expressed protein 2) Q8TDI7 FUNCTION: Probable ion channel required for the normal function of cochlear hair cells . Component of the hair cell's mechanotransduction (MET) machinery. Involved in mechanosensitive responses of the hair cells (By similarity).
67
RSPO4
R-spondin-4 (Roof plate-specific spondin-4) (hRspo4) Q2I0M5 FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors . Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (, ).
68
TMC4
Transmembrane channel-like protein 4 Q7Z404 FUNCTION: Probable ion channel.
69
TMCO5A
Transmembrane and coiled-coil domain-containing protein 5A Q8N6Q1 SUBCELLULAR LOCATION: Membrane .
70
TMCO5B
Transmembrane and coiled-coil domain-containing protein 5B A8MYB1 SUBCELLULAR LOCATION: Membrane .
71
GTF2H5
General transcription factor IIH subunit 5 (General transcription factor IIH polypeptide 5) (TFB5 ortholog) (TFIIH basal transcription factor complex TTD-A subunit) Q6ZYL4 FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell.
72
TMC6
Transmembrane channel-like protein 6 (Epidermodysplasia verruciformis protein 1) (Protein LAK-4) Q7Z403 FUNCTION: Probable ion channel.
73
RSRC1
Serine/Arginine-related protein 53 (SRrp53) (Arginine/serine-rich coiled-coil protein 1) Q96IZ7 FUNCTION: Has a role in alternative splicing and transcription regulation . Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing.
74
GTF3C1
General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) Q12789 FUNCTION: Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element. SUBCELLULAR LOCATION: Nucleus.
75
RSRC2
Arginine/serine-rich coiled-coil protein 2 Q7L4I2
76
RSRP1
Arginine/serine-rich protein 1 Q9BUV0
77
TFAP4
Transcription factor AP-4 (Activating enhancer-binding protein 4) (Class C basic helix-loop-helix protein 41) (bHLHc41) Q01664 FUNCTION: Transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'. SUBCELLULAR LOCATION: Nucleus.
78
TMCC3
Transmembrane and coiled-coil domain protein 3 Q9ULS5 SUBCELLULAR LOCATION: Endoplasmic reticulum membrane .
79
TMCO6
Transmembrane and coiled-coil domain-containing protein 6 Q96DC7 SUBCELLULAR LOCATION: Membrane .
80
TMED5
Transmembrane emp24 domain-containing protein 5 (p24 family protein gamma-2) (p24gamma2) (p28) Q9Y3A6 FUNCTION: Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Required for the maintenance of the Golgi apparatus; involved in protein exchange between Golgi stacks during assembly. Probably not required for COPI-vesicle-mediated retrograde transport. Note=Probably cycles between compartments of the early secretatory pathway.
81
TMED7
Transmembrane emp24 domain-containing protein 7 (p24 family protein gamma-3) (p24gamma3) (p27) Q9Y3B3 FUNCTION: Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Appears to play a role in the biosynthesis of secreted cargo including processing and post-translational modifications. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, cis-Golgi network membrane; Single-pass type I membrane protein. Endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein. Cytoplasmic vesicle, COPI-coated vesicle membrane . Note=Cycles between compartments of the early secretatory pathway.
82
TMED10
Transmembrane emp24 domain-containing protein 10 (21 kDa transmembrane-trafficking protein) (S31III125) (S31I125) (Tmp-21-I) (Transmembrane protein Tmp21) (p23) (p24 family protein delta-1) (p24delta1) (p24delta) P49755 FUNCTION: Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1 (By similarity). In COPI vesicle-mediated retrograde transport involved in the biogenesis of COPI vesicles and vesicle coat recruitment. On Golgi membranes, acts as primary receptor for ARF1-GDP which is involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2LR1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent of modulation of gamma-secretase activity). As part of the presenilin-dependent gamma-secretase complex regulates gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40 (Abeta40). Involved in organization of the Golgi apparatus. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Cycles between compartments of the early secretatory pathway.
83
ACAT1
Acetyl-CoA acetyltransferase, mitochondrial (EC 2.1.9) (Acetoacetyl-CoA thiolase) (T2) P24752 FUNCTION: This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (, , ). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (, , ). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA . Thereby, it plays a major role in ketone body metabolism (, , , ).
84
PRRG2
Transmembrane gamma-carboxyglutamic acid protein 2 (Proline-rich gamma-carboxyglutamic acid protein 2) (Proline-rich Gla protein 2) O14669 SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
85
PRRG4
Transmembrane gamma-carboxyglutamic acid protein 4 (Proline-rich gamma-carboxyglutamic acid protein 4) (Proline-rich Gla protein 4) Q9BZD6 FUNCTION: May control axon guidance across the CNS . Prevents the delivery of ROBO1 at the cell surface and downregulates its expression .
86
TMIGD1
Transmembrane and immunoglobulin domain-containing protein 1 Q6UXZ0 FUNCTION: May control cell-cell adhesion, cell migration and proliferation, cell morphology, and protects renal epithelial cells from oxidative cell injury to promote cell survival.
87
TMIGD2
Transmembrane and immunoglobulin domain-containing protein 2 (CD28 homolog) (Immunoglobulin and proline-rich receptor 1) (IGPR-1) Q96BF3 FUNCTION: Plays a role in cell-cell interaction, cell migration, and angiogenesis. Through interaction with HHLA2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.
88
TMIGD3
Transmembrane domain-containing protein TMIGD3 P0DMS9 FUNCTION: [Isoform 1]: Plays a suppressive role in osteosarcoma malignancy by inhibiting NF-kappa-B activity .
89
TMEM11
Transmembrane protein 11, mitochondrial (Protein PM1) (Protein PMI) P17152 FUNCTION: Plays a role in mitochondrial morphogenesis.
90
TMEM17
Transmembrane protein 17 Q86X19 FUNCTION: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
91
TMEM18
Transmembrane protein 18 Q96B42 FUNCTION: Transcription repressor. Sequence-specific ssDNA and dsDNA binding protein, with preference for GCT end CTG repeats. Cell migration modulator which enhances the glioma-specific migration ability of neural stem cells (NSC) and neural precursor cells (NPC).
92
TMEM26
Transmembrane protein 26 Q6ZUK4 SUBCELLULAR LOCATION: Membrane .
93
TMEM40
Transmembrane protein 40 Q8WWA1 SUBCELLULAR LOCATION: Membrane .
94
SYCE1L
Synaptonemal complex central element protein 1-like (Meiosis-related protein) A8MT33 FUNCTION: May be involved in meiosis.
95
TMEM44
Transmembrane protein 44 Q2T9K0 SUBCELLULAR LOCATION: Membrane .
96
TMEM52
Transmembrane protein 52 Q8NDY8 SUBCELLULAR LOCATION: Membrane .
97
TMEM60
Transmembrane protein 60 Q9H2L4 SUBCELLULAR LOCATION: Membrane .
98
TMEM61
Transmembrane protein 61 Q8N0U2 SUBCELLULAR LOCATION: Membrane .
99
TMEM65
Transmembrane protein 65 Q6PI78 FUNCTION: May play an important role in cardiac development and function. May regulate cardiac conduction and the function of the gap junction protein GJA1. May contribute to the stability and proper localization of GJA1 to cardiac intercalated disk thereby regulating gap junction communication (By similarity). May also play a role in the regulation of mitochondrial respiration and mitochondrial DNA copy number maintenance .
100
TMEM74
Transmembrane protein 74 Q96NL1 FUNCTION: Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction.
101
TMEM79
Transmembrane protein 79 (Mattrin) Q9BSE2 FUNCTION: Contributes to the epidermal integrity and skin barrier function. Plays a role in the lamellar granule (LG) secretory system and in the stratum corneum (SC) epithelial cell formation (By similarity).
102
TMEM81
Transmembrane protein 81 Q6P7N7 SUBCELLULAR LOCATION: Membrane .
103
TMEM82
Transmembrane protein 82 A0PJX8 SUBCELLULAR LOCATION: Membrane .
104
TMEM89
Transmembrane protein 89 A2RUT3 SUBCELLULAR LOCATION: Membrane .
105
TMPRSS4
Transmembrane protease serine 4 (EC 3.21.-) (Channel-activating protease 2) (CAPH2) (Membrane-type serine protease 2) (MT-SP2) Q9NRS4 FUNCTION: Probable protease. Seems to be capable of activating ENaC (By similarity).
106
TMPRSS5
Transmembrane protease serine 5 (EC 3.21.-) (Spinesin) Q9H3S3 FUNCTION: May play a role in hearing.
107
SYCP1
Synaptonemal complex protein 1 (SCP-1) (Cancer/testis antigen 8) (CT8) Q15431 FUNCTION: Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase. Required for normal assembly of the central element of the synaptonemal complexes. Required for normal centromere pairing during meiosis. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility.
108
TATDN1
Putative deoxyribonuclease TATDN1 (EC 3.21.-) (Hepatocarcinoma high expression protein) Q6P1N9 FUNCTION: Putative deoxyribonuclease.
109
TATDN2
Putative deoxyribonuclease TATDN2 (EC 3.21.-) Q93075 FUNCTION: Putative deoxyribonuclease.
110
RSU1
Ras suppressor protein 1 (RSP-1) (Rsu-1) Q15404 FUNCTION: Potentially plays a role in the Ras signal transduction pathway. Capable of suppressing v-Ras transformation in vitro.
111
ERVW-1
Syncytin-1 (Endogenous retrovirus group W member 1) (Env-W) (Envelope polyprotein gPr73) (Enverin) (HERV-7q Envelope protein) (HERV-W envelope protein) (HERV-W_7q21.2 provirus ancestral Env polyprotein) (Syncytin) [Cleaved into: Surface protein (SU) (gp50); Transmembrane protein (TM) (gp24)] Q9UQF0 FUNCTION: This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. May induce fusion through binding of SLC1A4 and SLC1A5 (, , ).
112
TRPM2
Transient receptor potential cation channel subfamily M member 2 (Estrogen-responsive element-associated gene 1 protein) (Long transient receptor potential channel 2) (LTrpC-2) (LTrpC2) (Transient receptor potential channel 7) (TrpC7) (Transient receptor potential melastatin 2) O94759 FUNCTION: [Isoform 1]: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (, , , , , , , , , , , , , , ). Functions as ligand-gated ion channel (, , , ). Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening (, , , , ). Extracellular calcium passes through the channel and increases channel activity . Contributes to Ca(2+) release from intracellular stores in response to ADP-ribose . Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (, ). Activated by moderate heat (35 to 40 degrees Celsius) . Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (, , , , , , , , , , ). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (, ). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) . Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) . Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels . Confers susceptibility to cell death following oxidative stress (, ).
113
TRPM4
Transient receptor potential cation channel subfamily M member 4 (hTRPM4) (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (Melastatin-4) Q8TD43 FUNCTION: Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization (, ). While it is activated by increase in intracellular Ca(2+), it is impermeable to it . Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Endoplasmic reticulum. Golgi apparatus.
114
TMUB1
Transmembrane and ubiquitin-like domain-containing protein 1 (Dendritic cell-derived ubiquitin-like protein) (DULP) (Hepatocyte odd protein shuttling protein) (Ubiquitin-like protein SB144) [Cleaved into: iHOPS] Q9BVT8 FUNCTION: Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR . Involved in positive regulation of AMPA-selective glutamate receptor GRIA2 recycling to the cell surface (By similarity). Acts as negative regulator of hepatocyte growth during regeneration (By similarity).
115
TMX3
Protein disulfide-isomerase TMX3 (EC 5.4.1) (Thioredoxin domain-containing protein 10) (Thioredoxin-related transmembrane protein 3) Q96JJ7 FUNCTION: Probable disulfide isomerase, which participates in the folding of proteins containing disulfide bonds. May act as a dithiol oxidase.
116
TMX4
Thioredoxin-related transmembrane protein 4 (Thioredoxin domain-containing protein 13) Q9H1E5 SUBCELLULAR LOCATION: Nucleus inner membrane .
117
TNFSF13B
Tumor necrosis factor ligand superfamily member 13B (B lymphocyte stimulator) (BLyS) (B-cell-activating factor) (BAFF) (Dendritic cell-derived TNF-like molecule) (TNF- and APOL-related leukocyte expressed ligand 1) (TALL-1) (CD antigen CD257) [Cleaved into: Tumor necrosis factor ligand superfamily member 13b, membrane form; Tumor necrosis factor ligand superfamily member 13b, soluble form] Q9Y275 FUNCTION: Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response. SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: [Tumor necrosis factor ligand superfamily member 13b, soluble form]: Secreted.
118
TRPM6
Transient receptor potential cation channel subfamily M member 6 (EC 2.11.1) (Channel kinase 2) (Melastatin-related TRP cation channel 6) Q9BX84 FUNCTION: Essential ion channel and serine/threonine-protein kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Isoforms of the type M6-kinase lack the ion channel region. SUBCELLULAR LOCATION: Cell membrane ; Multi-pass membrane protein.
119
TNFAIP2
Tumor necrosis factor alpha-induced protein 2 (TNF alpha-induced protein 2) (Primary response gene B94 protein) Q03169 FUNCTION: May play a role as a mediator of inflammation and angiogenesis.
120
TNFAIP3
Tumor necrosis factor alpha-induced protein 3 (TNF alpha-induced protein 3) (EC 2.2.-) (EC 3.19.12) (OTU domain-containing protein 7C) (Putative DNA-binding protein A20) (Zinc finger protein A20) [Cleaved into: A20p50; A20p37] P21580 FUNCTION: Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Lysosome.; SUBCELLULAR LOCATION: [A20p50]: Cytoplasm.
121
TNRC18
Trinucleotide repeat-containing gene 18 protein (Long CAG trinucleotide repeat-containing gene 79 protein) O15417
122
TNFSF10
Tumor necrosis factor ligand superfamily member 10 (Apo-2 ligand) (Apo-2L) (TNF-related apoptosis-inducing ligand) (Protein TRAIL) (CD antigen CD253) P50591 FUNCTION: Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (, ). Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.
123
STK19
Serine/threonine-protein kinase 19 (EC 2.11.1) (Protein G11) (Protein RP1) P49842 FUNCTION: Serine/threonine-protein kinase that acts as a key regulator of NRAS signaling by mediating phosphorylation of NRAS at 'Ser-89', thereby enhancing NRAS-binding to its downstream effectors.
124
STK25
Serine/threonine-protein kinase 25 (EC 2.11.1) (Ste20-like kinase) (Sterile 20/oxidant stress-response kinase 1) (SOK-1) (Ste20/oxidant stress response kinase 1) O00506 FUNCTION: Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Note=Localizes to the Golgi apparatus.
125
STK31
Serine/threonine-protein kinase 31 (EC 2.11.1) (Serine/threonine-protein kinase NYD-SPK) (Sugen kinase 396) (SgK396) Q9BXU1
126
TRPV3
Transient receptor potential cation channel subfamily V member 3 (TrpV3) (Vanilloid receptor-like 3) (VRL-3) Q8NET8 FUNCTION: Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
127
MYO7A
Unconventional myosin-VIIa Q13402 FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. In the retina, plays an important role in the renewal of the outer photoreceptor disks. Plays an important role in the distribution and migration of retinal pigment epithelial (RPE) melanosomes and phagosomes, and in the regulation of opsin transport in retinal photoreceptors. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity (By similarity). Motor protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing.
128
SLC16A14
Monocarboxylate transporter 14 (MCT 14) (Solute carrier family 16 member 14) Q7RTX9 FUNCTION: Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane.
129
MYO1G
Unconventional myosin-Ig [Cleaved into: Minor histocompatibility antigen HA-2 (mHag HA-2)] B0I1T2 FUNCTION: Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication. Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes. Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis.
130
PLCZ1
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 (EC 3.4.11) (Phosphoinositide phospholipase C-zeta-1) (Phospholipase C-zeta-1) (PLC-zeta-1) (Testis-development protein NYD-SP27) Q86YW0 FUNCTION: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)-dependent manner. Triggers intracellular Ca(2+) oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg-activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function.
131
RASSF3
Ras association domain-containing protein 3 Q86WH2 SUBCELLULAR LOCATION: Cytoplasm . Note=Localized to microtubules in vascular endothelial cells.
132
PRXL2A
Peroxiredoxin-like 2A (Peroxiredoxin-like 2 activated in M-CSF stimulated monocytes) (Protein PAMM) (Redox-regulatory protein FAM213A) Q9BRX8 FUNCTION: Involved in redox regulation of the cell (, ). Acts as an antioxidant (, ). Inhibits TNFSF11-induced NFKB1 and JUN activation and osteoclast differentiation . May affect bone resorption and help to maintain bone mass . Acts as a negative regulator of macrophage-mediated inflammation by inhibiting macrophage production of inflammatory cytokines, probably through suppression of the MAPK signaling pathway .
133
RFC1
Replication factor C subunit 1 (Activator 1 140 kDa subunit) (A1 140 kDa subunit) (Activator 1 large subunit) (Activator 1 subunit 1) (DNA-binding protein PO-GA) (Replication factor C 140 kDa subunit) (RF-C 140 kDa subunit) (RFC140) (Replication factor C large subunit) P35251 FUNCTION: The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Could play a role in DNA transcription regulation as well as DNA replication and/or repair. Can bind single- or double-stranded DNA. SUBCELLULAR LOCATION: Nucleus.
134
CAD
CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase (EC 6.5.5); Aspartate carbamoyltransferase (EC 2.3.2); Dihydroorotase (EC 3.2.3)] P27708 FUNCTION: This protein is a 'fusion' protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). Note=Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth.
135
REEP6
Receptor expression-enhancing protein 6 (Polyposis locus protein 1-like 1) Q96HR9 FUNCTION: Required for correct function and survival of retinal photoreceptors . Required for retinal development (By similarity). In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis (By similarity). May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane (By similarity).
136
RFX3
Transcription factor RFX3 (Regulatory factor X 3) P48380 FUNCTION: Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development. Essential for the differentiation of nodal monocilia and left-right asymmetry specification during embryogenesis. Required for the biogenesis of motile cilia by governing growth and beating efficiency of motile cells. Also required for ciliated ependymal cell differentiation. Regulates the expression of genes involved in ciliary assembly (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility (DNAH11, DNAH9 and DNAH5) (By similarity). Together with RFX6, participates in the differentiation of 4 of the 5 islet cell types during endocrine pancreas development, with the exception of pancreatic PP (polypeptide-producing) cells. Regulates transcription by forming a heterodimer with another RFX protein and binding to the X-box in the promoter of target genes . Represses transcription of MAP1A in non-neuronal cells but not in neuronal cells .
137
REELD1
Reelin domain-containing protein 1 A0A1B0GV85 SUBCELLULAR LOCATION: Membrane .
138
REPS1
RalBP1-associated Eps domain-containing protein 1 (RalBP1-interacting protein 1) Q96D71 FUNCTION: May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. Note=Colocalize with ITSN1 at the plasma membrane in structures that are most probably clathrin-coated pits.
139
RAB22A
Ras-related protein Rab-22A (Rab-22) Q9UL26 FUNCTION: Plays a role in endocytosis and intracellular protein transport. Mediates trafficking of TF from early endosomes to recycling endosomes . Required for NGF-mediated endocytosis of NTRK1, and subsequent neurite outgrowth . Binds GTP and GDP and has low GTPase activity. Alternates between a GTP-bound active form and a GDP-bound inactive form .
140
RAB33A
Ras-related protein Rab-33A (Small GTP-binding protein S10) Q14088 SUBCELLULAR LOCATION: Cell membrane .
141
RAB3GAP1
Rab3 GTPase-activating protein catalytic subunit (RAB3 GTPase-activating protein 130 kDa subunit) (Rab3-GAP p130) (Rab3-GAP) Q15042 FUNCTION: Probable catalytic subunit of a GTPase activating protein that has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. Specifically converts active Rab3-GTP to the inactive form Rab3-GDP. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters. Note=In neurons, it is enriched in the synaptic soluble fraction.
142
RBAK
RB-associated KRAB zinc finger protein (RB-associated KRAB repressor) (hRBaK) (Zinc finger protein 769) Q9NYW8 FUNCTION: May repress E2F-dependent transcription. May promote AR-dependent transcription.
143
RAB3GAP2
Rab3 GTPase-activating protein non-catalytic subunit (RGAP-iso) (Rab3 GTPase-activating protein 150 kDa subunit) (Rab3-GAP p150) (Rab3-GAP150) (Rab3-GAP regulatory subunit) Q9H2M9 FUNCTION: Regulatory subunit of a GTPase activating protein that has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. Rab3 GTPase-activating complex specifically converts active Rab3-GTP to the inactive form Rab3-GDP. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters. SUBCELLULAR LOCATION: Cytoplasm. Note=In neurons, it is enriched in the synaptic soluble fraction.
144
SLC49A3
Solute carrier family 49 member A3 (Major facilitator superfamily domain-containing protein 7) (Myosin light polypeptide 5 regulatory protein) (MYL5) Q6UXD7 SUBCELLULAR LOCATION: Membrane .
145
SYMPK
Symplekin Q92797 FUNCTION: Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3'-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity.
146
TBX5
T-box transcription factor TBX5 (T-box protein 5) Q99593 FUNCTION: DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation (, , , , , ). Binds to the core DNA motif of NPPA promoter .
147
SIRPG
Signal-regulatory protein gamma (SIRP-gamma) (CD172 antigen-like family member B) (Signal-regulatory protein beta-2) (SIRP-b2) (SIRP-beta-2) (CD antigen CD172g) Q9P1W8 FUNCTION: Probable immunoglobulin-like cell surface receptor. On binding with CD47, mediates cell-cell adhesion. Engagement on T-cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation and costimulates T-cell activation.
148
SRPRB
Signal recognition particle receptor subunit beta (SR-beta) (Protein APMCF1) Q9Y5M8 FUNCTION: Component of the SRP (signal recognition particle) receptor. Ensures, in conjunction with the signal recognition particle, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system. Has GTPase activity. May mediate the membrane association of SRPR (By similarity).
149
SLC6A14
Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) (Amino acid transporter ATB0+) (Solute carrier family 6 member 14) Q9UN76 FUNCTION: Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
150
SIRT7
NAD-dependent protein deacetylase sirtuin-7 (EC 2.1.286) (NAD-dependent protein deacylase sirtuin-7) (EC 2.1.-) (Regulatory protein SIR2 homolog 7) (SIR2-like protein 7) Q9NRC8 FUNCTION: NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase and deglutarylase), depending on the context (, , , ). Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (, ). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression (, ). H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors; SIRT7 thereby acts as a transcription repressor . Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells . Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac) in the context of nucleosomes . Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53 (, , , , , , , , ). Enriched in nucleolus where it stimulates transcription activity of the RNA polymerase I complex (, , ). Acts by mediating the deacetylation of the RNA polymerase I subunit POLR1E/PAF53, thereby promoting the association of RNA polymerase I with the rDNA promoter region and coding region (, , ). In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription . Required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis . Promotes pre-ribosomal RNA (pre-rRNA) cleavage at the 5'-terminal processing site by mediating deacetylation of RRP9/U3-55K, a core subunit of the U3 snoRNP complex . Mediates 'Lys-37' deacetylation of Ran, thereby regulating the nuclear export of NF-kappa-B subunit RELA/p65 . Acts as a regulator of DNA damage repair by mediating deacetylation of ATM during the late stages of DNA damage response, promoting ATM dephosphorylation and deactivation . Suppresses the activity of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes by mediating deacetylation of DDB1, which prevents the interaction between DDB1 and CUL4 (CUL4A or CUL4B) . Activates RNA polymerase II transcription by mediating deacetylation of CDK9, thereby promoting 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA polymerase II . Deacetylates FBL, promoting histone-glutamine methyltransferase activity of FBL . Acts as a regulator of mitochondrial function by catalyzing deacetylation of GABPB1 (By similarity). Regulates Akt/AKT1 activity by mediating deacetylation of FKBP5/FKBP51 . Required to prevent R-loop-associated DNA damage and transcription-associated genomic instability by mediating deacetylation and subsequent activation of DDX21, thereby overcoming R-loop-mediated stalling of RNA polymerases . In addition to protein deacetylase activity, also acts as protein-lysine deacylase (, , ). Acts as a protein depropionylase by mediating depropionylation of Osterix (SP7), thereby regulating bone formation by osteoblasts (By similarity). Acts as a histone deglutarylase by mediating deglutarylation of histone H4 on 'Lys-91' (H4K91glu); a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes . Acts as a histone desuccinylase: in response to DNA damage, recruited to DNA double-strand breaks (DSBs) and catalyzes desuccinylation of histone H3 on 'Lys-122' (H3K122succ), thereby promoting chromatin condensation and DSB repair . Also promotes DSB repair by promoting H3K18Ac deacetylation, regulating non-homologous end joining (NHEJ) (By similarity). Along with its role in DNA repair, required for chromosome synapsis during prophase I of female meiosis by catalyzing H3K18Ac deacetylation (By similarity). Involved in transcriptional repression of LINE-1 retrotransposon via H3K18Ac deacetylation, and promotes their association with the nuclear lamina . Required to stabilize ribosomal DNA (rDNA) heterochromatin and prevent cellular senescence induced by rDNA instability . Acts as a negative regulator of SIRT1 by preventing autodeacetylation of SIRT1, restricting SIRT1 deacetylase activity (By similarity).
151
TBX6
T-box transcription factor TBX6 (T-box protein 6) O95947 FUNCTION: T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal. Acts in part by down-regulating, a specific enhancer (N1) of SOX2, to inhibit neural development. Seems to play also an essential role in left/right axis determination and acts through effects on Notch signaling around the node as well as through an effect on the morphology and motility of the nodal cilia (By similarity).
152
TIMM44
Mitochondrial import inner membrane translocase subunit TIM44 O43615 FUNCTION: Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Recruits mitochondrial HSP70 to drive protein translocation into the matrix using ATP as an energy source.
153
SGK2
Serine/threonine-protein kinase Sgk2 (EC 2.11.1) (Serum/glucocorticoid-regulated kinase 2) Q9HBY8 FUNCTION: Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, survival and proliferation. Up-regulates Na(+) channels: SCNN1A/ENAC, K(+) channels: KCNA3/Kv1.3, KCNE1 and KCNQ1, amino acid transporter: SLC6A19, glutamate transporter: SLC1A6/EAAT4, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase.
154
SPACA9
Sperm acrosome-associated protein 9 Q96E40 SUBCELLULAR LOCATION: Cytoplasm .
155
TOMM20
Mitochondrial import receptor subunit TOM20 homolog (Mitochondrial 20 kDa outer membrane protein) (Outer mitochondrial membrane receptor Tom20) Q15388 FUNCTION: Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore (By similarity). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases.
156
KNSTRN
Small kinetochore-associated protein (SKAP) (Kinetochore-localized astrin-binding protein) (Kinastrin) (Kinetochore-localized astrin/SPAG5-binding protein) (TRAF4-associated factor 1) Q9Y448 FUNCTION: Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase . Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (, ). The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule-kinetochore attachments . Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division . May be involved in UV-induced apoptosis via its interaction with PRPF19; however, these results need additional evidences .
157
TOMM7
Mitochondrial import receptor subunit TOM7 homolog (Translocase of outer membrane 7 kDa subunit homolog) Q9P0U1 FUNCTION: Required for assembly and stability of the TOM complex. Positive regulator of PRKN translocation to damaged mitochondria. Acts probably by stabilizing PINK1 on the outer membrane of depolarized mitochondria.
158
SSBP2
Single-stranded DNA-binding protein 2 (Sequence-specific single-stranded-DNA-binding protein 2) P81877 SUBCELLULAR LOCATION: Nucleus .
159
SH2D5
SH2 domain-containing protein 5 Q6ZV89 FUNCTION: May be involved in synaptic plasticity regulation through the control of Rac-GTP levels.
160
SYN1
Synapsin-1 (Brain protein 4.1) (Synapsin I) P17600 FUNCTION: Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level. SUBCELLULAR LOCATION: Cell junction, synapse. Golgi apparatus .
161
SSNA1
Sjoegren syndrome nuclear autoantigen 1 (Nuclear autoantigen of 14 kDa) O43805 SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome .
162
SAP18
Histone deacetylase complex subunit SAP18 (18 kDa Sin3-associated polypeptide) (2HOR0202) (Cell growth-inhibiting gene 38 protein) (Sin3-associated polypeptide p18) O00422 FUNCTION: Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function.
163
GHRH
Somatoliberin (Growth hormone-releasing factor) (GRF) (Growth hormone-releasing hormone) (GHRH) (Somatocrinin) (Somatorelin) (Sermorelin) P01286 FUNCTION: GRF is released by the hypothalamus and acts on the adenohypophyse to stimulate the secretion of growth hormone. SUBCELLULAR LOCATION: Secreted.
164
SHPRH
E3 ubiquitin-protein ligase SHPRH (EC 2.2.27) (EC 3.4.-) (RING-type E3 ubiquitin transferase SHPRH) (SNF2, histone-linker, PHD and RING finger domain-containing helicase) Q149N8 FUNCTION: E3 ubiquitin-protein ligase involved in DNA repair. Upon genotoxic stress, accepts ubiquitin from the UBE2N-UBE2V2 E2 complex and transfers it to 'Lys-164' of PCNA which had been monoubiquitinated by UBE2A/B-RAD18, promoting the formation of non-canonical poly-ubiquitin chains linked through 'Lys-63'.
165
SLC9C2
Sodium/hydrogen exchanger 11 (Na(+)/H(+) exchanger 11) (NHE-11) (Solute carrier family 9 member 11) (Solute carrier family 9 member C2) Q5TAH2 FUNCTION: Involved in pH regulation. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
166
SLITRK2
SLIT and NTRK-like protein 2 Q9H156 FUNCTION: It is involved in synaptogenesis and promotes excitatory synapse differentiation (, ). Suppresses neurite outgrowth (By similarity).
167
ST6GALNAC2
Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (EC 2.99.3) (GalNAc alpha-2,6-sialyltransferase II) (ST6GalNAc II) (ST6GalNAcII) (SThM) (Sialyltransferase 7B) (SIAT7-B) Q9UJ37 FUNCTION: Catalyzes the transfer of N-acetylneuraminyl groups onto glycan chains in glycoproteins.
168
SEC14L5
SEC14-like protein 5 O43304
169
SWT1
Transcriptional protein SWT1 Q5T5J6
170
STK32B
Serine/threonine-protein kinase 32B (EC 2.11.1) (Yet another novel kinase 2) Q9NY57
171
ST5
Suppression of tumorigenicity 5 protein (DENN domain-containing protein 2B) (HeLa tumor suppression 1) P78524 FUNCTION: [Isoform 1]: May be involved in cytoskeletal organization and tumorogenicity. Seems to be involved in a signaling transduction pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR trafficking from recycling endosomes back to the cell membrane .
172
SCARA3
Scavenger receptor class A member 3 (Cellular stress response gene protein) Q6AZY7 FUNCTION: Seems to protect cells by scavenging oxidative molecules or harmful products of oxidation. Note=Endoplasmic reticulum and/or Golgi.
173
TMEM220
Transmembrane protein 220 Q6QAJ8 SUBCELLULAR LOCATION: Membrane .
174
SCFD1
Sec1 family domain-containing protein 1 (SLY1 homolog) (Sly1p) (Syntaxin-binding protein 1-like 2) Q8WVM8 FUNCTION: Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi (By similarity).
175
TASOR2
Protein TASOR 2 Q5VWN6
176
SMIM4
Small integral membrane protein 4 Q8WVI0 SUBCELLULAR LOCATION: Membrane .
177
TMEM231
Transmembrane protein 231 Q9H6L2 FUNCTION: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
178
CHGB
Secretogranin-1 (Chromogranin-B) (CgB) (Secretogranin I) (SgI) [Cleaved into: PE-11; GAWK peptide; CCB peptide] P05060 FUNCTION: Secretogranin-1 is a neuroendocrine secretory granule protein, which may be the precursor for other biologically active peptides. SUBCELLULAR LOCATION: Secreted. Note=Neuroendocrine and endocrine secretory granules.
179
SCG2
Secretogranin-2 (Chromogranin-C) (Secretogranin II) (SgII) [Cleaved into: Secretoneurin (SN); Manserin] P13521 FUNCTION: Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules. SUBCELLULAR LOCATION: Secreted. Note=Neuroendocrine and endocrine secretory granules.
180
STXBP5L
Syntaxin-binding protein 5-like (Lethal(2) giant larvae protein homolog 4) (Tomosyn-2) Q9Y2K9 FUNCTION: Plays a role in vesicle trafficking and exocytosis inhibition. In pancreatic beta-cells, inhibits insulin secretion probably by interacting with and regulating STX1A and STX4, key t-SNARE proteins involved in the fusion of insulin granules to the plasma membrane. Plays also a role in neurotransmitter release by inhibiting basal acetylcholine release from axon terminals and by preventing synaptic fatigue upon repetitive stimulation (By similarity). Promotes as well axonal outgrowth .
181
TMEM251
Transmembrane protein 251 Q8N6I4 SUBCELLULAR LOCATION: Membrane .
182
TMEM253
Transmembrane protein 253 P0C7T8 SUBCELLULAR LOCATION: Membrane .
183
TENT5B
Terminal nucleotidyltransferase 5B (EC 2.7.-) Q96A09 FUNCTION: Probable nucleotidyltransferase that may act as a non-canonical poly(A) RNA polymerase.
184
TMEM260
Transmembrane protein 260 Q9NX78 SUBCELLULAR LOCATION: Membrane .
185
TMEM263
Transmembrane protein 263 Q8WUH6 SUBCELLULAR LOCATION: Membrane .
186
TMEM266
Transmembrane protein 266 (hTMEM266) (HV1-related protein 1) (HsHVRP1) Q2M3C6 FUNCTION: Voltage-sensor protein present on the post-synaptic side of glutamatergic mossy fibers and granule cells in the cerebellum (, ). Despite the presence of a voltage-sensor segment, does not form a functional ion channel and its precise role remains unclear (, ). Undergoes both rapid and slow structural rearrangements in response to changes in voltage . Contains a zinc-binding site that can regulate the slow conformational transition .
187
TM2D1
TM2 domain-containing protein 1 (Amyloid-beta-binding protein) (hBBP) Q9BX74 FUNCTION: May participate in amyloid-beta-induced apoptosis via its interaction with beta-APP42.
188
TM2D2
TM2 domain-containing protein 2 (Beta-amyloid-binding protein-like protein 1) (BBP-like protein 1) Q9BX73 SUBCELLULAR LOCATION: Membrane .
189
TM2D3
TM2 domain-containing protein 3 (Beta-amyloid-binding protein-like protein 2) (BBP-like protein 2) Q9BRN9 SUBCELLULAR LOCATION: Membrane .
190
TEX10
Testis-expressed protein 10 Q9NXF1 FUNCTION: Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes . Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit .
191
TEX11
Testis-expressed protein 11 Q8IYF3 FUNCTION: Regulator of crossing-over during meiosis. Involved in initiation and/or maintenance of chromosome synapsis and formation of crossovers.
192
STEAP1B
STEAP family member 1B Q6NZ63 SUBCELLULAR LOCATION: Membrane .
193
WARS
Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] P23381 FUNCTION: Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression. SUBCELLULAR LOCATION: Cytoplasm.
194
TEX14
Inactive serine/threonine-protein kinase TEX14 (Protein kinase-like protein SgK307) (Sugen kinase 307) (Testis-expressed sequence 14) (Testis-expressed sequence 14 protein) Q8IWB6 FUNCTION: Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro (By similarity).
195
TEX15
Testis-expressed protein 15 (Cancer/testis antigen 42) (CT42) Q9BXT5 FUNCTION: Required during spermatogenesis for normal chromosome synapsis and meiotic recombination in germ cells. Necessary for formation of DMC1 and RAD51 foci on meiotic chromosomes, suggesting a specific role in DNA double-stranded break repair.
196
TMEM38B
Trimeric intracellular cation channel type B (TRIC-B) (TRICB) (Transmembrane protein 38B) Q9NVV0 FUNCTION: Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.
197
TEX26
Testis-expressed protein 26 Q8N6G2
198
TMEM39B
Transmembrane protein 39B Q9GZU3 SUBCELLULAR LOCATION: Membrane .
199
TEX30
Testis-expressed protein 30 Q5JUR7
200
TEX33
Testis-expressed protein 33 O43247
201
TEX38
Testis-expressed protein 38 (ATPAF1 antisense RNA 1) (ATPAF1 antisense gene protein 1) Q6PEX7 SUBCELLULAR LOCATION: Membrane .
202
TMEM45A
Transmembrane protein 45A (DNA polymerase-transactivated protein 4) (Dermal papilla-derived protein 7) Q9NWC5 SUBCELLULAR LOCATION: Membrane .
203
TEX50
Testis-expressed protein 50 A0A1B0GTY4 SUBCELLULAR LOCATION: Membrane .
204
TEX51
Testis-expressed protein 51 A0A1B0GUA7 SUBCELLULAR LOCATION: Membrane .
205
TEX52
Testis-expressed protein 52 A6NCN8
206
TMEM50B
Transmembrane protein 50B (HCV p7-trans-regulated protein 3) P56557 SUBCELLULAR LOCATION: Endoplasmic reticulum membrane .
207
TMEM59L
Transmembrane protein 59-like (Brain-specific membrane-anchored protein) Q9UK28 FUNCTION: Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of APP. Inhibits APP transport to the cell surface and further shedding.
208
TM6SF2
Transmembrane 6 superfamily member 2 Q9BZW4 FUNCTION: Regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content (, ). May function as sterol isomerase .
209
TMEM74B
Transmembrane protein 74B Q9NUR3 SUBCELLULAR LOCATION: Membrane .
210
RSPH1
Radial spoke head 1 homolog (Cancer/testis antigen 79) (CT79) (Male meiotic metaphase chromosome-associated acidic protein) (Meichroacidin) (Testis-specific gene A2 protein) Q8WYR4 FUNCTION: May play an important role in male meiosis (By similarity). It is necessary for proper building of the axonemal central pair and radial spokes.
211
GTF2A1L
TFIIA-alpha and beta-like factor (General transcription factor II A, 1-like factor) Q9UNN4 FUNCTION: May function as a testis specific transcription factor. Binds DNA in conjunction with GTF2A2 and TBP (the TATA-binding protein) and together with GTF2A2, allows mRNA transcription. Note=Mainly localizes in the annulus and partly in acrosomal cap area of spermatozoa.
212
TM9SF1
Transmembrane 9 superfamily member 1 (MP70 protein family member) (hMP70) O15321 FUNCTION: Plays an essential role in autophagy.
213
RSPO1
R-spondin-1 (Roof plate-specific spondin-1) (hRspo1) Q2MKA7 FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors . Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 .
214
TM9SF2
Transmembrane 9 superfamily member 2 (p76) Q99805 FUNCTION: In the intracellular compartments, may function as a channel or small molecule transporter.
215
RSPO2
R-spondin-2 (Roof plate-specific spondin-2) (hRspo2) Q6UXX9 FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (, , ). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form .
216
TMA7
Translation machinery-associated protein 7 (Coiled-coil domain-containing protein 72) Q9Y2S6
217
TMC1
Transmembrane channel-like protein 1 (Transmembrane cochlear-expressed protein 1) Q8TDI8 FUNCTION: Probable ion channel required for the normal function of cochlear hair cells.
218
GTF2H2
General transcription factor IIH subunit 2 (Basic transcription factor 2 44 kDa subunit) (BTF2 p44) (General transcription factor IIH polypeptide 2) (TFIIH basal transcription factor complex p44 subunit) Q13888 FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. The N-terminus of GTF2H2 interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter.
219
TMC3
Transmembrane channel-like protein 3 Q7Z5M5 FUNCTION: Probable ion channel.
220
GTF2H3
General transcription factor IIH subunit 3 (Basic transcription factor 2 34 kDa subunit) (BTF2 p34) (General transcription factor IIH polypeptide 3) (TFIIH basal transcription factor complex p34 subunit) Q13889 FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.
221
GTF2H4
General transcription factor IIH subunit 4 (Basic transcription factor 2 52 kDa subunit) (BTF2 p52) (General transcription factor IIH polypeptide 4) (TFIIH basal transcription factor complex p52 subunit) Q92759 FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. SUBCELLULAR LOCATION: Nucleus.
222
TMC5
Transmembrane channel-like protein 5 Q6UXY8 FUNCTION: Probable ion channel.
223
TGIF2LX
Homeobox protein TGIF2LX (TGF-beta-induced transcription factor 2-like protein) (TGFB-induced factor 2-like protein, X-linked) (TGIF-like on the X) Q8IUE1 FUNCTION: May have a transcription role in testis. SUBCELLULAR LOCATION: Nucleus .
224
TMC8
Transmembrane channel-like protein 8 (Epidermodysplasia verruciformis protein 2) Q8IU68 FUNCTION: Probable ion channel.
225
BRF1
Transcription factor IIIB 90 kDa subunit (TFIIIB90) (hTFIIIB90) (B-related factor 1) (BRF-1) (hBRF) (TAF3B2) (TATA box-binding protein-associated factor, RNA polymerase III, subunit 2) Q92994 FUNCTION: General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter. SUBCELLULAR LOCATION: Nucleus .
226
GTF3C2
General transcription factor 3C polypeptide 2 (TF3C-beta) (Transcription factor IIIC 110 kDa subunit) (TFIIIC 110 kDa subunit) (TFIIIC110) (Transcription factor IIIC subunit beta) Q8WUA4 FUNCTION: Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. May play a direct role in stabilizing interactions of TFIIIC2 with TFIIIC1. SUBCELLULAR LOCATION: Nucleus.
227
GTF3C3
General transcription factor 3C polypeptide 3 (Transcription factor IIIC 102 kDa subunit) (TFIIIC 102 kDa subunit) (TFIIIC102) (Transcription factor IIIC subunit gamma) (TF3C-gamma) Q9Y5Q9 FUNCTION: Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters. SUBCELLULAR LOCATION: Nucleus.
228
GTF3C4
General transcription factor 3C polypeptide 4 (EC 2.1.48) (TF3C-delta) (Transcription factor IIIC 90 kDa subunit) (TFIIIC 90 kDa subunit) (TFIIIC90) (Transcription factor IIIC subunit delta) Q9UKN8 FUNCTION: Essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA, tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin. Has histone acetyltransferase activity (HAT) with unique specificity for free and nucleosomal H3. May cooperate with GTF3C5 in facilitating the recruitment of TFIIIB and RNA polymerase through direct interactions with BRF1, POLR3C and POLR3F. May be localized close to the A box. SUBCELLULAR LOCATION: Nucleus.
229
GTF3C6
General transcription factor 3C polypeptide 6 (Transcription factor IIIC 35 kDa subunit) (TFIIIC 35 kDa subunit) (TFIIIC35) (Transcription factor IIIC subunit 6) Q969F1 FUNCTION: Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.
230
RELA
Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) Q04206 FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells . The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression.
231
TCF7L1
Transcription factor 7-like 1 (HMG box transcription factor 3) (TCF-3) Q9HCS4 FUNCTION: Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance. SUBCELLULAR LOCATION: Nucleus.
232
TCF7L2
Transcription factor 7-like 2 (HMG box transcription factor 4) (T-cell-specific transcription factor 4) (T-cell factor 4) (TCF-4) (hTCF-4) Q9NQB0 FUNCTION: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. Note=Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies.
233
TMCC2
Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) O75069 FUNCTION: May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE.
234
TMCO3
Transmembrane and coiled-coil domain-containing protein 3 (Putative LAG1-interacting protein) Q6UWJ1 FUNCTION: Probable Na(+)/H(+) antiporter.
235
TMCO4
Transmembrane and coiled-coil domain-containing protein 4 Q5TGY1 SUBCELLULAR LOCATION: Membrane .
236
TMED1
Transmembrane emp24 domain-containing protein 1 (Interleukin-1 receptor-like 1 ligand) (Putative T1/ST2 receptor-binding protein) (p24 family protein gamma-1) (Tp24) (p24gamma1) Q13445 FUNCTION: Potential role in vesicular protein trafficking, mainly in the early secretory pathway. May act as a cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and may be involved in vesicle coat formation at the cytoplasmic side. SUBCELLULAR LOCATION: Cell membrane .
237
TMED2
Transmembrane emp24 domain-containing protein 2 (Membrane protein p24A) (p24) (p24 family protein beta-1) (p24beta1) Q15363 FUNCTION: Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing.
238
TMED3
Transmembrane emp24 domain-containing protein 3 (Membrane protein p24B) (p24 family protein gamma-4) (p24gamma4) (p26) Q9Y3Q3 FUNCTION: Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network.
239
TMED6
Transmembrane emp24 domain-containing protein 6 (p24 family protein gamma-5) (p24gamma5) Q8WW62 SUBCELLULAR LOCATION: Endoplasmic reticulum membrane .
240
TMED8
Protein TMED8 Q6PL24
241
TMED9
Transmembrane emp24 domain-containing protein 9 (GMP25) (Glycoprotein 25L2) (p24 family protein alpha-2) (p24alpha2) (p25) Q9BVK6 FUNCTION: Appears to be involved in vesicular protein trafficking, mainly in the early secretory pathway. In COPI vesicle-mediated retrograde transport involved in the coatomer recruitment to membranes of the early secretory pathway. Increases coatomer-dependent activity of ARFGAP2. Thought to play a crucial role in the specific retention of p24 complexes in cis-Golgi membranes; specifically contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network. May be involved in organization of intracellular membranes, such as of the ER-Golgi intermediate compartment and the Golgi apparatus. Involved in ER localization of PTPN2 isoform PTPB. Note=Cycles between compartments of the early secretatory pathway.
242
PRRG1
Transmembrane gamma-carboxyglutamic acid protein 1 (Proline-rich gamma-carboxyglutamic acid protein 1) (Proline-rich Gla protein 1) O14668 SUBCELLULAR LOCATION: Membrane .
243
TMLHE
Trimethyllysine dioxygenase, mitochondrial (EC 1.14.11.8) (Epsilon-trimethyllysine 2-oxoglutarate dioxygenase) (Epsilon-trimethyllysine hydroxylase) (TML hydroxylase) (TML-alpha-ketoglutarate dioxygenase) (TML dioxygenase) (TMLD) Q9NVH6 FUNCTION: Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (, ).
244
TMEM19
Transmembrane protein 19 Q96HH6 SUBCELLULAR LOCATION: Membrane .
245
TMEM25
Transmembrane protein 25 Q86YD3 SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane .
246
TMEM33
Transmembrane protein 33 (Protein DB83) (SHINC-3) P57088 FUNCTION: Acts as a regulator of the tubular endoplasmic reticulum (ER) network. Suppresses the RTN3/4-induced formation of the ER tubules . Positively regulates PERK-mediated and IRE1-mediated unfolded protein response signaling .
247
TMEM47
Transmembrane protein 47 (Brain cell membrane protein 1) (Transmembrane 4 superfamily member 10) Q9BQJ4 FUNCTION: Regulates cell junction organization in epithelial cells. May play a role in the transition from adherens junction to tight junction assembly. May regulate F-actin polymerization required for tight junctional localization dynamics and affect the junctional localization of PARD6B. During podocyte differentiation may negatively regulate activity of FYN and subsequently the abundance of nephrin (By similarity).
248
TMEM53
Transmembrane protein 53 Q6P2H8 SUBCELLULAR LOCATION: Membrane .
249
SYCP2L
Synaptonemal complex protein 2-like (SCP-2-like) (145 kDa nucleolar protein homolog) (hsNO145) Q5T4T6 FUNCTION: Oocyte-specific protein that localizes to centromeres at the dictyate stage and regulates the survival of primordial oocytes.
250
TMEM59
Transmembrane protein 59 (Liver membrane-bound protein) Q9BXS4 FUNCTION: Acts as a regulator of autophagy in response to S.aureus infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C). Acts by interacting with ATG16L1, leading to promote a functional complex between LC3 and ATG16L1 and promoting LC3 lipidation and subsequent activation of autophagy (, ). Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of several proteins such as APP, BACE1, SEAP or PRNP . Inhibits APP transport to the cell surface and further shedding .
251
TMEM62
Transmembrane protein 62 Q0P6H9 SUBCELLULAR LOCATION: Membrane .
252
TMEM64
Transmembrane protein 64 Q6YI46 FUNCTION: Positively regulates TNFSF11-induced osteoclast differentiation. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with SERCA2 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation. Negatively regulates osteoblast differentiation and positively regulates adipocyte differentiation via modulation of the canonical Wnt signaling pathway. Mediates the switch in lineage commitment to osteogenesis rather than to adipogenesis in mesenchymal stem cells by negatively regulating the expression, activity and nuclear localization of CTNNB1.
253
TMEM68
Transmembrane protein 68 Q96MH6 SUBCELLULAR LOCATION: Membrane .
254
TMEM69
Transmembrane protein 69 Q5SWH9 SUBCELLULAR LOCATION: Membrane .
255
TMEM88
Transmembrane protein 88 Q6PEY1 FUNCTION: Inhibits the Wnt/beta-catenin signaling pathway. Crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte development.
256
TMEM8B
Transmembrane protein 8B (Nasopharyngeal carcinoma-associated gene 6 protein) (Protein NAG-5) (Protein NGX6) A6NDV4 FUNCTION: May function as a regulator of the EGFR pathway. Probable tumor suppressor which may function in cell growth, proliferation and adhesion. Note=Also detected in mitochondrion and endoplasmic reticulum .
257
TMEM95
Transmembrane protein 95 Q3KNT9 SUBCELLULAR LOCATION: Membrane .
258
TMEM98
Transmembrane protein 98 (Protein TADA1) Q9Y2Y6 FUNCTION: Functions as a negative regulator of MYRF in oligodendrocyte differentiation and myelination. Interacts with the C-terminal of MYRF inhibiting MYRF self-cleavage and N-fragment nuclear translocation. The secreted form promotes differentiation of T helper 1 cells (Th1).
259
TMEM9B
Transmembrane protein 9B Q9NQ34 FUNCTION: Enhances production of proinflammatory cytokines induced by TNF, IL1B, and TLR ligands. Has a role in TNF activation of both the NF-kappaB and MAPK pathways.
260
TMOD1
Tropomodulin-1 (Erythrocyte tropomodulin) (E-Tmod) P28289 FUNCTION: Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton. May play an important role in regulating the organization of actin filaments by preferentially binding to a specific tropomyosin isoform at its N-terminus.
261
TMOD2
Tropomodulin-2 (Neuronal tropomodulin) (N-Tmod) Q9NZR1 FUNCTION: Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).
262
SYCE2
Synaptonemal complex central element protein 2 (Central element synaptonemal complex protein 1) Q6PIF2 FUNCTION: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination (By similarity).
263
TMOD3
Tropomodulin-3 (Ubiquitous tropomodulin) (U-Tmod) Q9NYL9 FUNCTION: Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).
264
STIMATE
Store-operated calcium entry regulator STIMATE (STIM-activating enhancer encoded by TMEM110) (Transmembrane protein 110) Q86TL2 FUNCTION: Acts as a regulator of store-operated Ca(2+) entry (SOCE) at junctional sites that connect the endoplasmic reticulum (ER) and plasma membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical ER (, ). SOCE is a Ca(2+) influx following depletion of intracellular Ca(2+) stores . Acts by interacting with STIM1, promoting STIM1 conformational switch . Involved in STIM1 relocalization to ER-PM junctions . Contributes to the maintenance and reorganization of store-dependent ER-PM junctions .
265
SYCE3
Synaptonemal complex central element protein 3 (Testis highly expressed gene 2 protein) (THEG-2) A1L190 FUNCTION: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for chromosome loading of the central element-specific SCS proteins, and for initiating synapsis between homologous chromosomes. Chromosome loading appears to require SYCP1. Required for fertility.
266
PSMB3
Proteasome subunit beta type-3 (EC 3.25.1) (Proteasome chain 13) (Proteasome component C10-II) (Proteasome theta chain) P49720 FUNCTION: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).
267
SLC10A2
Ileal sodium/bile acid cotransporter (Apical sodium-dependent bile acid transporter) (ASBT) (Ileal Na(+)/bile acid cotransporter) (Ileal sodium-dependent bile acid transporter) (IBAT) (ISBT) (Na(+)-dependent ileal bile acid transporter) (Sodium/taurocholate cotransporting polypeptide, ileal) (Solute carrier family 10 member 2) Q12908 FUNCTION: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
268
MT-RNR1
Mitochondrial-derived peptide MOTS-c (Mitochondrial open reading frame of the 12S rRNA-c) A0A0C5B5G6 FUNCTION: Regulates insulin sensitivity and metabolic homeostasis. Inhibits the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK). Protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity.
269
POSTN
Periostin (PN) (Osteoblast-specific factor 2) (OSF-2) Q15063 FUNCTION: Induces cell attachment and spreading and plays a role in cell adhesion . Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX (By similarity).
270
PNMT
Phenylethanolamine N-methyltransferase (PNMTase) (EC 2.1.28) (Noradrenaline N-methyltransferase) P11086 FUNCTION: Converts noradrenaline to adrenaline.
271
MAP2K6
Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3) P52564 FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. Note=Binds to microtubules.
272
PLPBP
Pyridoxal phosphate homeostasis protein (PLP homeostasis protein) (Proline synthase co-transcribed bacterial homolog protein) (Pyridoxal phosphate-binding protein) O94903 FUNCTION: Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6.
273
MTURN
Maturin (Maturin neural progenitor differentiation regulator protein homolog) (Protein Ells1) Q8N3F0 FUNCTION: Promotes megakaryocyte differentiation by enhancing ERK and JNK signaling as well as up-regulating RUNX1 and FLI1 expression . Represses NF-kappa-B transcriptional activity by inhibiting phosphorylation of RELA at 'Ser-536' . May be involved in early neuronal development (By similarity).
274
PLA2G6
85/88 kDa calcium-independent phospholipase A2 (CaI-PLA2) (EC 3.1.4) (Group VI phospholipase A2) (GVI PLA2) (Intracellular membrane-associated calcium-independent phospholipase A2 beta) (iPLA2-beta) (Patatin-like phospholipase domain-containing protein 9) (PNPLA9) O60733 FUNCTION: Catalyzes the release of fatty acids from phospholipids. It has been implicated in normal phospholipid remodeling, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin production. May participate in fas mediated apoptosis and in regulating transmembrane ion flux in glucose-stimulated B-cells. Has a role in cardiolipin (CL) deacylation. Required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actin polymerization at the pseudopods.; FUNCTION: Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of iPLA2 activity. SUBCELLULAR LOCATION: [Isoform LH-iPLA2]: Membrane; Peripheral membrane protein. Note=Recruited to the membrane-enriched pseudopod upon MCP1/CCL2 stimulation in monocytes.; SUBCELLULAR LOCATION: [Isoform SH-iPLA2]: Cytoplasm.
275
PLPP7
Inactive phospholipid phosphatase 7 (Phosphatidic acid phosphatase type 2 domain-containing protein 3) Q8NBV4 FUNCTION: Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling. Has no detectable enzymatic activity (By similarity).
276
MUC16
Mucin-16 (MUC-16) (Ovarian cancer-related tumor marker CA125) (CA-125) (Ovarian carcinoma antigen CA125) Q8WXI7 FUNCTION: Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Secreted, extracellular space. Note=May be liberated into the extracellular space following the phosphorylation of the intracellular C-terminus which induces the proteolytic cleavage and liberation of the extracellular domain.
277
MUC22
Mucin-22 (Panbronchiolitis-related mucin-like protein 1) E2RYF6 SUBCELLULAR LOCATION: Membrane .
278
PIP4K2B
Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (EC 2.1.149) (1-phosphatidylinositol 5-phosphate 4-kinase 2-beta) (Diphosphoinositide kinase 2-beta) (Phosphatidylinositol 5-phosphate 4-kinase type II beta) (PI(5)P 4-kinase type II beta) (PIP4KII-beta) (PtdIns(5)P-4-kinase isoform 2-beta) P78356 FUNCTION: Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
279
PLSCR1
Phospholipid scramblase 1 (PL scramblase 1) (Ca(2+)-dependent phospholipid scramblase 1) (Erythrocyte phospholipid scramblase) (MmTRA1b) O15162 FUNCTION: May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.; FUNCTION: May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes. May contribute to cytokine-regulated cell proliferation and differentiation. SUBCELLULAR LOCATION: Cell membrane .
280
PIK3CG
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3-kinase subunit gamma) (PI3K-gamma) (PI3Kgamma) (PtdIns-3-kinase subunit gamma) (EC 2.1.153) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma) (PtdIns-3-kinase subunit p110-gamma) (p110gamma) (Phosphoinositide-3-kinase catalytic gamma polypeptide) (Serine/threonine protein kinase PIK3CG) (EC 2.11.1) (p120-PI3K) P48736 FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.
281
PLEKHA4
Pleckstrin homology domain-containing family A member 4 (PH domain-containing family A member 4) (Phosphoinositol 3-phosphate-binding protein 1) (PEPP-1) Q9H4M7 FUNCTION: Binds specifically to phosphatidylinositol 3-phosphate (PtdIns3P), but not to other phosphoinositides.
282
PPP1R17
Protein phosphatase 1 regulatory subunit 17 (G-substrate) O96001 FUNCTION: Inhibits phosphatase activities of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) complexes.
283
PLEKHG1
Pleckstrin homology domain-containing family G member 1 Q9ULL1
284
PPP1R3D
Protein phosphatase 1 regulatory subunit 3D (Protein phosphatase 1 regulatory subunit 6) (PP1 subunit R6) (Protein phosphatase 1-binding subunit R6) O95685 FUNCTION: Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis.
285
PLEKHH2
Pleckstrin homology domain-containing family H member 2 Q8IVE3 FUNCTION: In the kidney glomerulus may play a role in linking podocyte foot processes to the glomerular basement membrane. May be involved in stabilization of F-actin by attenuating its depolymerization. Can recruit TGFB1I1 from focal adhesions to podocyte lamellipodia. SUBCELLULAR LOCATION: Cytoplasm . Note=Localizes to foot process of podocytes. Localization to peripheral regions of lamellipodia seems to be dependent on PI3K.
286
PLEKHH3
Pleckstrin homology domain-containing family H member 3 (PH domain-containing family H member 3) Q7Z736
287
PLEKHG3
Pleckstrin homology domain-containing family G member 3 (PH domain-containing family G member 3) A1L390
288
PLEKHA7
Pleckstrin homology domain-containing family A member 7 (PH domain-containing family A member 7) Q6IQ23 FUNCTION: Required for zonula adherens biogenesis and maintenance . Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site . Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33 .
289
PPP1R3A
Protein phosphatase 1 regulatory subunit 3A (Protein phosphatase 1 glycogen-associated regulatory subunit) (Protein phosphatase type-1 glycogen targeting subunit) (RG1) Q16821 FUNCTION: Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase (By similarity).
290
PLEKHG4
Puratrophin-1 (Pleckstrin homology domain-containing family G member 4) (PH domain-containing family G member 4) (Purkinje cell atrophy-associated protein 1) Q58EX7 FUNCTION: Possible role in intracellular signaling and cytoskeleton dynamics at the Golgi.
291
PKN1
Serine/threonine-protein kinase N1 (EC 2.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) Q16512 FUNCTION: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.
292
PRKRIP1
PRKR-interacting protein 1 Q9H875 FUNCTION: Required for pre-mRNA splicing as component of the spliceosome (, ). Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity (By similarity).
293
POP5
Ribonuclease P/MRP protein subunit POP5 (hPop5) (EC 3.26.5) Q969H6 FUNCTION: Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends (, ). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences .
294
POMP
Proteasome maturation protein (Proteassemblin) (Protein UMP1 homolog) (hUMP1) (Voltage-gated K channel beta subunit 4.1) Q9Y244 FUNCTION: Molecular chaperone essential for the assembly of standard proteasomes and immunoproteasomes. Degraded after completion of proteasome maturation. Mediates the association of 20S preproteasome with the endoplasmic reticulum. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Microsome membrane.
295
RAN
GTP-binding nuclear protein Ran (Androgen receptor-associated protein 24) (GTPase Ran) (Ras-like protein TC4) (Ras-related nuclear protein) P62826 FUNCTION: GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (, , , , , , , , ). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (, , , , , , , , , ). Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (, , ). Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins . RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (, ). Required for normal progress through mitosis (, , ). The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules . Acts as a negative regulator of the kinase activity of VRK1 and VRK2 . Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases .
296
ROBO2
Roundabout homolog 2 Q9HCK4 FUNCTION: Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. SUBCELLULAR LOCATION: Membrane .
297
ROBO4
Roundabout homolog 4 (Magic roundabout) Q8WZ75 FUNCTION: Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity).
298
RIDA
2-iminobutanoate/2-iminopropanoate deaminase (EC 3.99.10) (14.5 kDa translational inhibitor protein) (hp14.5) (p14.5) (Heat-responsive protein 12) (Reactive intermediate imine deaminase A homolog) (Translation inhibitor L-PSP ribonuclease) (UK114 antigen homolog) P52758 FUNCTION: Catalyzes the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism. May facilitate the release of ammonia from these potentially toxic reactive metabolites, reducing their impact on cellular components. It may act on enamine/imine intermediates formed by several types of pyridoxal-5'-phosphate-dependent dehydratases including L-threonine dehydratase.
299
RIF1
Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) Q5UIP0 FUNCTION: Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (, ). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (, ). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs . Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs . In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase . Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity).
300
RRP36
Ribosomal RNA processing protein 36 homolog Q96EU6 FUNCTION: Involved in the early processing steps of the pre-rRNA in the maturation pathway leading to the 18S rRNA. Note=Concentrated in the fibrillar region of the nucleolus.
301
POLR1E
DNA-directed RNA polymerase I subunit RPA49 (RNA polymerase I subunit A49) (DNA-directed RNA polymerase I subunit E) (RNA polymerase I-associated factor 1) (RNA polymerase I-associated factor 53) Q9GZS1 FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors . Appears to be involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBTF/UBF .
302
RNF182
E3 ubiquitin-protein ligase RNF182 (EC 2.2.27) (RING finger protein 182) (RING-type E3 ubiquitin transferase RNF182) Q8N6D2 FUNCTION: E3 ubiquitin-protein ligase that mediates the ubiquitination of ATP6V0C and targets it to degradation via the ubiquitin-proteasome pathway . Plays also a role in the inhibition of TLR-triggered innate immune response by mediating 'Lys'-48-linked ubiquitination and subsequent degradation of NF-kappa-B component RELA .
303
RAB6A
Ras-related protein Rab-6A (Rab-6) P20340 FUNCTION: Protein transport. Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER). Has a low GTPase activity. Involved in COPI-independent retrograde transport from the Golgi to the ER .
304
RNASE6
Ribonuclease K6 (RNase K6) (EC 3.27.-) Q93091 FUNCTION: Ribonuclease which shows a preference for the pyrimidines uridine and cytosine (, ). Has potent antibacterial activity against a range of Gram-positive and Gram-negative bacteria, including P.aeruginosa, A.baumanii, M.luteus, S.aureus, E.faecalis, E.faecium, S.saprophyticus and E.coli (, ). Causes loss of bacterial membrane integrity, and also promotes agglutination of Gram-negative bacteria . Probably contributes to urinary tract sterility . Bactericidal activity is independent of RNase activity .
305
RAB35
Ras-related protein Rab-35 (GTP-binding protein RAY) (Ras-related protein Rab-1C) Q15286 FUNCTION: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes.
306
RASA2
Ras GTPase-activating protein 2 (GTPase-activating protein 1m) (GAP1m) Q15283 FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4). SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
307
PTPRD
Receptor-type tyrosine-protein phosphatase delta (Protein-tyrosine phosphatase delta) (R-PTP-delta) (EC 3.3.48) P23468 FUNCTION: Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically. Involved in pre-synaptic differentiation through interaction with SLITRK2. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
308
SCML2
Sex comb on midleg-like protein 2 Q9UQR0 FUNCTION: Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development (By similarity).
309
TPPP2
Tubulin polymerization-promoting protein family member 2 (Protein p25-beta) (TPPP/p18) P59282 FUNCTION: Probable regulator of microtubule dynamics required for sperm motility (Probable). In contrast to other members of the family, has no microtubule bundling activity .
310
SMRP1
Spermatid-specific manchette-related protein 1 (Ciliated bronchial epithelial protein 1) (Testis development protein NYD-SP22) Q8NCR6 FUNCTION: May play a role in spermatogenesis (By similarity). May be involved in differentiation or function of ciliated cells.
311
RASL11A
Ras-like protein family member 11A Q6T310 FUNCTION: Regulator of rDNA transcription. Acts in cooperation UBF/UBTF and positively regulates RNA polymerase I transcription (By similarity).
312
AGMAT
Agmatinase, mitochondrial (EC 3.3.11) (Agmatine ureohydrolase) (AUH) Q9BSE5 SUBCELLULAR LOCATION: Mitochondrion.
313
TRPC5OS
Putative uncharacterized protein TRPC5OS (TRPC5 opposite strand protein) (TRPC5-antisense RNA 1) A6NMA1
314
TRIM42
Tripartite motif-containing protein 42 Q8IWZ5
315
TRIB1
Tribbles homolog 1 (TRB-1) (G-protein-coupled receptor-induced gene 2 protein) (GIG-2) (SKIP1) Q96RU8 FUNCTION: Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase . The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain . Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA . Binds selectively the recognition sequence of CEBPA . Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (By similarity). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (, ).
316
SERINC2
Serine incorporator 2 (Tumor differentially expressed protein 2-like) Q96SA4 SUBCELLULAR LOCATION: Membrane .
317
SYT2
Synaptotagmin-2 (Synaptotagmin II) (SytII) Q8N9I0 FUNCTION: Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (By similarity). Plays a role in dendrite formation by melanocytes .
318
SPANXN4
Sperm protein associated with the nucleus on the X chromosome N4 (Nuclear-associated protein SPAN-Xn4) (SPANX-N4) (SPANX family member N4) Q5MJ08
319
SPOCK2
Testican-2 (SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2) Q92563 FUNCTION: May participate in diverse steps of neurogenesis. Binds calcium. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix .
320
SERF1A; SERF1B
Small EDRK-rich factor 1 (Protein 4F5) (h4F5) (SMA modifier 1) O75920 FUNCTION: Positive regulator of amyloid protein aggregation and proteotoxicity (, , ). Induces conformational changes in amyloid proteins, such as APP, HTT, and SNCA, driving them into compact formations preceding the formation of aggregates (, , ).
321
TNFSF13
Tumor necrosis factor ligand superfamily member 13 (A proliferation-inducing ligand) (APRIL) (TNF- and APOL-related leukocyte expressed ligand 2) (TALL-2) (TNF-related death ligand 1) (TRDL-1) (CD antigen CD256) O75888 FUNCTION: Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA. Plays a role in the regulation of tumor cell growth. May be involved in monocyte/macrophage-mediated immunological processes.
322
SPATA9
Spermatogenesis-associated protein 9 (Testis development protein NYD-SP16) Q9BWV2 FUNCTION: May play a role in testicular development/spermatogenesis and may be an important factor in male infertility.
323
SF3B4
Splicing factor 3B subunit 4 (Pre-mRNA-splicing factor SF3b 49 kDa subunit) (Spliceosome-associated protein 49) (SAP 49) Q15427 FUNCTION: Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex . SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA . May also be involved in the assembly of the 'E' complex. SF3B4 has been found in complex 'B' and 'C' as well . Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron .
324
SLC35B4
UDP-xylose and UDP-N-acetylglucosamine transporter (Solute carrier family 35 member B4) (YEA4 homolog) Q969S0 FUNCTION: Sugar transporter that specifically mediates the transport of UDP-xylose (UDP-Xyl) and UDP-N-acetylglucosamine (UDP-GlcNAc) from cytosol into Golgi.
325
SMIM27
Small integral membrane protein 27 (TOPORS antisense RNA 1) A0A1B0GUW7 SUBCELLULAR LOCATION: Membrane .
326
SLC38A3
Sodium-coupled neutral amino acid transporter 3 (N-system amino acid transporter 1) (Na(+)-coupled neutral amino acid transporter 3) (Solute carrier family 38 member 3) (System N amino acid transporter 1) Q99624 FUNCTION: Sodium-dependent amino acid/proton antiporter. Mediates electrogenic cotransport of glutamine and sodium ions in exchange for protons. Also recognizes histidine, asparagine and alanine. May mediate amino acid transport in either direction under physiological conditions. May play a role in nitrogen metabolism and synaptic transmission.
327
RSC1A1
Regulatory solute carrier protein family 1 member 1 (Transporter regulator RS1) (hRS1) Q92681 FUNCTION: Mediates transcriptional and post-transcriptional regulation of SLC5A1. Inhibits a dynamin and PKC-dependent exocytotic pathway of SLC5A1. Also involved in transcriptional regulation of SLC22A2. Exhibits glucose-dependent, short-term inhibition of SLC5A1 and SLC22A2 by inhibiting the release of vesicles from the trans-Golgi network. Note=Localizes at the inner side of the plasma membrane.
328
SMIM29
Small integral membrane protein 29 (Protein LBH) Q86T20 SUBCELLULAR LOCATION: Membrane .
329
TAF1D
TATA box-binding protein-associated factor RNA polymerase I subunit D (RNA polymerase I-specific TBP-associated factor 41 kDa) (TAFI41) (TATA box-binding protein-associated factor 1D) (TBP-associated factor 1D) (Transcription initiation factor SL1/TIF-IB subunit D) Q9H5J8 FUNCTION: Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.
330
SHISA9
Protein shisa-9 B4DS77 FUNCTION: Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses (By similarity).
331
SLPI
Antileukoproteinase (ALP) (BLPI) (HUSI-1) (Mucus proteinase inhibitor) (MPI) (Protease inhibitor WAP4) (Secretory leukocyte protease inhibitor) (Seminal proteinase inhibitor) (WAP four-disulfide core domain protein 4) P03973 FUNCTION: Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (, , , , , ). Modulates the inflammatory and immune responses after bacterial infection, and after infection by the intracellular parasite L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS) (By similarity). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses (, ). Has antimicrobial activity against mycobacteria, but not against salmonella. Contributes to normal resistance against infection by M.tuberculosis. Required for normal resistance to infection by L.major. Required for normal wound healing, probably by preventing tissue damage by limiting protease activity (By similarity). Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells .
332
S100A10
Protein S100-A10 (Calpactin I light chain) (Calpactin-1 light chain) (Cellular ligand of annexin II) (S100 calcium-binding protein A10) (p10 protein) (p11) P60903 FUNCTION: Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.
333
SMAD6
Mothers against decapentaplegic homolog 6 (MAD homolog 6) (Mothers against DPP homolog 6) (SMAD family member 6) (SMAD 6) (Smad6) (hSMAD6) O43541 FUNCTION: Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.
334
TIRAP
Toll/interleukin-1 receptor domain-containing adapter protein (TIR domain-containing adapter protein) (Adaptor protein Wyatt) (MyD88 adapter-like protein) (MyD88-2) P58753 FUNCTION: Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6. Note=Colocalizes with DAB2IP at the plasma membrane.
335
TCF20
Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) Q9UGU0 FUNCTION: Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator.
336
TRBJ2-4
T cell receptor beta joining 2-4 A0A0A0MT87 FUNCTION: J region of the variable domain of T cell receptor (TR) beta chain that participates in the antigen recognition . Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens . Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation . The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity .
337
TKT
Transketolase (TK) (EC 2.1.1) P29401 FUNCTION: Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.
338
TEKT5
Tektin-5 Q96M29 FUNCTION: May be a structural component of the sperm flagellum.
339
TNS1
Tensin-1 Q9HBL0 FUNCTION: Involved in fibrillar adhesion formation. May be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Note=Localized at cell periphery preferentially to fibrillar adhesions than focal adhesions. Translocates from the cell edge to cell center in an ITGB1BP1-dependent manner.
340
TMEM141
Transmembrane protein 141 Q96I45 SUBCELLULAR LOCATION: Membrane .
341
RRP9
U3 small nucleolar RNA-interacting protein 2 (RRP9 homolog) (U3 small nucleolar ribonucleoprotein-associated 55 kDa protein) (U3 snoRNP-associated 55 kDa protein) (U3-55K) O43818 FUNCTION: Component of a nucleolar small nuclear ribonucleoprotein particle (snoRNP) thought to participate in the processing and modification of pre-ribosomal RNA (pre-rRNA).
342
RS1
Retinoschisin (X-linked juvenile retinoschisis protein) O15537 FUNCTION: Binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides (By similarity). May play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells . Required for normal structure and function of the retina .
343
UBE2V1
Ubiquitin-conjugating enzyme E2 variant 1 (UEV-1) (CROC-1) (TRAF6-regulated IKK activator 1 beta Uev1A) Q13404 FUNCTION: Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production . Note=Excluded from the nucleolus.
344
XRCC4
DNA repair protein XRCC4 (X-ray repair cross-complementing protein 4) Q13426 FUNCTION: Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
345
TULP1
Tubby-related protein 1 (Tubby-like protein 1) O00294 FUNCTION: Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages.
346
ZNF512B
Zinc finger protein 512B Q96KM6 FUNCTION: May be involved in transcriptional regulation. SUBCELLULAR LOCATION: Nucleus .
347
USP42
Ubiquitin carboxyl-terminal hydrolase 42 (EC 3.19.12) (Deubiquitinating enzyme 42) (Ubiquitin thioesterase 42) (Ubiquitin-specific-processing protease 42) Q9H9J4 FUNCTION: Deubiquitinating enzyme which may play an important role during spermatogenesis.
348
UCK2
Uridine-cytidine kinase 2 (UCK 2) (EC 2.1.48) (Cytidine monophosphokinase 2) (Testis-specific protein TSA903) (Uridine monophosphokinase 2) Q9BZX2 FUNCTION: Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate. Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor. Can also phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine.
349
UCP3
Mitochondrial uncoupling protein 3 (UCP 3) (Solute carrier family 25 member 9) P55916 FUNCTION: UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation. As a result, energy is dissipated in the form of heat. May play a role in the modulation of tissue respiratory control. Participates in thermogenesis and energy balance. SUBCELLULAR LOCATION: Mitochondrion inner membrane .
350
ZCCHC7
Zinc finger CCHC domain-containing protein 7 (TRAMP-like complex RNA-binding factor ZCCHC7) Q8N3Z6 SUBCELLULAR LOCATION: Nucleus, nucleolus .
351
ZC3HAV1
Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) Q7Z2W4 FUNCTION: Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs).
352
ZDHHC12
Probable palmitoyltransferase ZDHHC12 (EC 2.1.225) (Zinc finger DHHC domain-containing protein 12) (DHHC-12) (Zinc finger protein 400) Q96GR4 SUBCELLULAR LOCATION: Membrane .
353
UGT3A2
UDP-glucuronosyltransferase 3A2 (UDPGT 3A2) (EC 2.1.17) Q3SY77 FUNCTION: UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).
354
VWA2
von Willebrand factor A domain-containing protein 2 (A domain-containing protein similar to matrilin and collagen) (AMACO) (Colon cancer secreted protein 2) (CCSP-2) Q5GFL6 SUBCELLULAR LOCATION: Secreted.
355
ZFP90
Zinc finger protein 90 homolog (Zfp-90) (Zinc finger protein 756) Q8TF47 FUNCTION: Inhibits the transcriptional repressor activity of REST by inhibiting its binding to DNA, thereby derepressing transcription of REST target genes.
356
MTHFD2L
Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein) (MTHFD2-like) [Includes: NAD-dependent methylenetetrahydrofolate dehydrogenase (EC 1.1.15); Methenyltetrahydrofolate cyclohydrolase (EC 3.4.9)] Q9H903 SUBCELLULAR LOCATION: Mitochondrion inner membrane .
357
RAB31
Ras-related protein Rab-31 (Ras-related protein Rab-22B) Q13636 FUNCTION: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Required for the integrity and for normal function of the Golgi apparatus and the trans-Golgi network. Plays a role in insulin-stimulated translocation of GLUT4 to the cell membrane. Plays a role in M6PR transport from the trans-Golgi network to endosomes. Plays a role in the internalization of EGFR from the cell membrane into endosomes. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.
358
RAB6C
Ras-related protein Rab-6C (Rab6-like protein WTH3) Q9H0N0 FUNCTION: May be involved in the regulation of centrosome duplication and cell cycle progression.
359
RAB32
Ras-related protein Rab-32 Q13637 FUNCTION: Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission . Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis . Plays an important role in the control of melanin production and melanosome biogenesis . In concert with RAB38, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity).
360
RAB5IF
Uncharacterized protein RAB5IF (Rab5-interacting protein) (RIP5) Q9BUV8
361
RPS14
40S ribosomal protein S14 (Small ribosomal subunit protein uS11) P62263
362
RAD17
Cell cycle checkpoint protein RAD17 (hRad17) (RF-C/activator 1 homolog) O75943 FUNCTION: Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination. Note=Phosphorylated form redistributes to discrete nuclear foci upon DNA damage.
363
RAD21
Double-strand-break repair protein rad21 homolog (hHR21) (Nuclear matrix protein 1) (NXP-1) (SCC1 homolog) [Cleaved into: 64-kDa C-terminal product (64-kDa carboxy-terminal product) (65-kDa carboxy-terminal product)] O60216 FUNCTION: [Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions . The cohesin complex may also play a role in spindle pole assembly during mitosis . In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter . May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity).
364
RARRES2
Retinoic acid receptor responder protein 2 (Chemerin) (RAR-responsive protein TIG2) (Tazarotene-induced gene 2 protein) Q99969 FUNCTION: Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Its other ligands include G protein-coupled receptor 1 (GPR1) and chemokine receptor-like 2 (CCRL2). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a proinflammatory adipokine, causing an increase in secretion of proinflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin.
365
RDH10
Retinol dehydrogenase 10 (EC 1.1.300) (Short chain dehydrogenase/reductase family 16C member 4) Q8IZV5 FUNCTION: Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinol to all-trans-retinal. Has no detectable activity towards 11-cis-retinol, 9-cis-retinol and 13-cis-retinol.
366
PVRIG
Transmembrane protein PVRIG (CD112 receptor) (CD112R) (Poliovirus receptor-related immunoglobulin domain-containing protein) Q6DKI7 FUNCTION: Cell surface receptor for NECTIN2. May act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. Following interaction with NECTIN2, inhibits T-cell proliferation. Competes with CD226 for NECTIN2-binding.
367
PYGB
Glycogen phosphorylase, brain form (EC 2.1.1) P11216 FUNCTION: Glycogen phosphorylase that regulates glycogen mobilization . Phosphorylase is an important allosteric enzyme in carbohydrate metabolism . Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates . However, all known phosphorylases share catalytic and structural properties .
368
RFLNB
Refilin-B (Regulator of filamin protein B) (RefilinB) Q8N5W9 FUNCTION: Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in the formation of cartilaginous skeletal elements.
369
REEP3
Receptor expression-enhancing protein 3 Q6NUK4 FUNCTION: Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes.
370
RFNG
Beta-1,3-N-acetylglucosaminyltransferase radical fringe (EC 2.1.222) (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) Q9Y644 FUNCTION: Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in enhancement of NOTCH1 activation by DLL1 and JAG1. May be involved in limb formation and in neurogenesis.
371
RGMA
Repulsive guidance molecule A (RGM domain family member A) Q96B86 FUNCTION: Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.
372
RBPJL
Recombining binding protein suppressor of hairless-like protein (Transcription factor RBP-L) Q9UBG7 FUNCTION: Putative transcription factor, which cooperates with EBNA2 to activate transcription.
373
PTTG1
Securin (Esp1-associated protein) (Pituitary tumor-transforming gene 1 protein) (Tumor-transforming protein 1) (hPTTG) O95997 FUNCTION: Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation. SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
374
CD96
T-cell surface protein tactile (Cell surface antigen CD96) (T cell-activated increased late expression protein) (CD antigen CD96) P40200 FUNCTION: May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
375
S100A8
Protein S100-A8 (Calgranulin-A) (Calprotectin L1L subunit) (Cystic fibrosis antigen) (CFAG) (Leukocyte L1 complex light chain) (Migration inhibitory factor-related protein 8) (MRP-8) (p8) (S100 calcium-binding protein A8) (Urinary stone protein band A) P05109 FUNCTION: S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity. SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway.
376
SS18L2
SS18-like protein 2 (SYT homolog 2) Q9UHA2
377
SLC5A2
Sodium/glucose cotransporter 2 (Na(+)/glucose cotransporter 2) (Low affinity sodium-glucose cotransporter) (Solute carrier family 5 member 2) P31639 FUNCTION: Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.; FUNCTION: Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
378
SEC31A
Protein transport protein Sec31A (ABP125) (ABP130) (SEC31-like protein 1) (SEC31-related protein A) (Web1-like protein) O94979 FUNCTION: Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER) . The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity).
379
TMEM207
Transmembrane protein 207 Q6UWW9 SUBCELLULAR LOCATION: Membrane .
380
SLC22A24
Solute carrier family 22 member 24 Q8N4F4 SUBCELLULAR LOCATION: Membrane .
381
SMARCE1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (BRG1-associated factor 57) (BAF57) Q969G3 FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells.
382
STAM
Signal transducing adapter molecule 1 (STAM-1) Q92783 FUNCTION: Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. SUBCELLULAR LOCATION: Cytoplasm .
383
SMG1
Serine/threonine-protein kinase SMG1 (SMG-1) (hSMG-1) (EC 2.11.1) (61E3.4) (Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein) Q96Q15 FUNCTION: Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ.
384
TAPT1
Transmembrane anterior posterior transformation protein 1 homolog (Cytomegalovirus partial fusion receptor) Q6NXT6 FUNCTION: Plays a role in primary cilia formation . May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patterning during development (By similarity). May be involved in cartilage and bone development (By similarity). May play a role in the differentiation of cranial neural crest cells (By similarity).
385
STARD6
StAR-related lipid transfer protein 6 (START domain-containing protein 6) (StARD6) P59095 FUNCTION: May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols (By similarity).
386
STARD3
StAR-related lipid transfer protein 3 (Metastatic lymph node gene 64 protein) (MLN 64) (Protein CAB1) (START domain-containing protein 3) (StARD3) Q14849 FUNCTION: Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes (, , , ). Creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum via interaction with VAPA and VAPB (, ). Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes . May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane (, ). However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes . Does not activate transcriptional cholesterol sensing . Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina .
387
SLC26A8
Testis anion transporter 1 (Anion exchange transporter) (Solute carrier family 26 member 8) Q96RN1 FUNCTION: Acts as a DIDS-sensitive anion exchanger mediating chloride, sulfate and oxalate transport. May fulfill critical anion exchange functions in male germ line during meiosis and hence may play a role in spermatogenesis. May be involved in a new regulatory pathway linking sulfate transport to RhoGTPase signaling in male germ cells. A critical component of the sperm annulus that is essential for correct sperm tail differentiation and motility and hence male fertility. May form a molecular complex involved in the regulation of chloride and bicarbonate ions fluxes during sperm capacitation.
388
SLC27A4
Long-chain fatty acid transport protein 4 (FATP-4) (Fatty acid transport protein 4) (EC 6.1.-) (Solute carrier family 27 member 4) Q6P1M0 FUNCTION: Involved in translocation of long-chain fatty acids (LFCA) across the plasma membrane. Appears to be the principal fatty acid transporter in small intestinal enterocytes. Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis. Has acyl-CoA ligase activity for long-chain and very-long-chain fatty acids (VLCFAs). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (By similarity).
389
SMCHD1
Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMC hinge domain-containing protein 1) (EC 3.1.-) A6NHR9 FUNCTION: Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture (By similarity). Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments (By similarity). Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin . Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X (By similarity). Required to facilitate Xist RNA spreading (By similarity). Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus . Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation . Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks (, ). Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair .
390
STAT4
Signal transducer and activator of transcription 4 Q14765 FUNCTION: Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated into the nucleus in response to phosphorylation.
391
SMO
Smoothened homolog (SMO) (Protein Gx) Q99835 FUNCTION: G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia . Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity).
392
TRPS1
Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) Q9UHF7 FUNCTION: Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes.
393
STRADB
STE20-related kinase adapter protein beta (STRAD beta) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein) (CALS-21) (ILP-interacting protein) (Pseudokinase ALS2CR2) Q9C0K7 FUNCTION: Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation (By similarity).
394
TMEM183B
Transmembrane protein 183B Q1AE95 SUBCELLULAR LOCATION: Membrane .
395
STRA8
Stimulated by retinoic acid gene 8 protein homolog Q7Z7C7 FUNCTION: Meiosis-inducer required for the transition into meiosis for both female and male germ cells. In female germ cells, required for premeiotic DNA replication and subsequent events in meiotic prophase. During spermatogenesis, next to its role in meiotic initiation, promotes (but is not required for) spermatogonial differentiation. Can associate with DNA (possibly in an indirect manner), and in vitro can activate DNA transcription (By similarity).
396
THSD1
Thrombospondin type-1 domain-containing protein 1 (Transmembrane molecule with thrombospondin module) Q9NS62 SUBCELLULAR LOCATION: [Isoform 1]: Membrane .; SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
397
STUM
Protein stum homolog Q69YW2 SUBCELLULAR LOCATION: Membrane .
398
THUMPD1
THUMP domain-containing protein 1 Q9NXG2 FUNCTION: Functions as a tRNA-binding adapter to mediate NAT10-dependent tRNA acetylation .
399
TRIM28
Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Q13263 FUNCTION: Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) . Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells . Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) . In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing . The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions . Acts as a corepressor for ZFP568 (By similarity).
400
TAS2R3
Taste receptor type 2 member 3 (T2R3) Q9NYW6 FUNCTION: Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
401
TIGD7
Tigger transposable element-derived protein 7 Q6NT04 SUBCELLULAR LOCATION: Nucleus .
402
OCLM
Oculomedin (Trabecular meshwork-inducible stretch response protein) (TISR) Q9Y5M6
403
FAU
40S ribosomal protein S30 (Small ribosomal subunit protein eS30) P62861
404
ZNF233
Zinc finger protein 233 A6NK53 FUNCTION: May be involved in transcriptional regulation. SUBCELLULAR LOCATION: Nucleus .
405
ZNF207
BUB3-interacting and GLEBS motif-containing protein ZNF207 (BuGZ) (hBuGZ) (Zinc finger protein 207) O43670 FUNCTION: Kinetochore- and microtubule-binding protein that plays a key role in spindle assembly (, , ). ZNF207/BuGZ is mainly composed of disordered low-complexity regions and undergoes phase transition or coacervation to form temperature-dependent liquid droplets. Coacervation promotes microtubule bundling and concentrates tubulin, promoting microtubule polymerization and assembly of spindle and spindle matrix by concentrating its building blocks . Also acts as a regulator of mitotic chromosome alignment by mediating the stability and kinetochore loading of BUB3 (, ). Mechanisms by which BUB3 is protected are unclear: according to a first report, ZNF207/BuGZ may act by blocking ubiquitination and proteasomal degradation of BUB3 . According to another report, the stabilization is independent of the proteasome .
406
ZNF160
Zinc finger protein 160 (Zinc finger protein HZF5) (Zinc finger protein Kr18) (HKr18) Q9HCG1 FUNCTION: May be involved in transcriptional regulation. SUBCELLULAR LOCATION: Nucleus .
407
ZNF281
Zinc finger protein 281 (GC-box-binding zinc finger protein 1) (Transcription factor ZBP-99) (Zinc finger DNA-binding protein 99) Q9Y2X9 FUNCTION: Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs (By similarity). Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes.
408
ZNF296
Zinc finger protein 296 (ZFP296) (Zinc finger protein 342) Q8WUU4 FUNCTION: May be a transcriptional corepressor with KLF4.
409
ZNF788P
Putative KRAB domain-containing protein ZNF788 (Zinc finger family member 788, pseudogene) Q6ZQV5
410
ZNF366
Zinc finger protein 366 (Dendritic cell-specific transcript protein) (DC-SCRIPT) Q8N895 FUNCTION: Has transcriptional repression activity. Acts as corepressor of ESR1; the function seems to involve CTBP1 and histone deacetylases.
411
TSC1
Hamartin (Tuberous sclerosis 1 protein) Q92574 FUNCTION: In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (, ). Seems not to be required for TSC2 GAP activity towards RHEB . Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling (By similarity). Acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 . Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity . Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins . Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (, ).
412
ZNF503
Zinc finger protein 503 Q96F45 FUNCTION: May function as a transcriptional repressor.
413
ZNF529
Zinc finger protein 529 Q6P280 FUNCTION: May be involved in transcriptional regulation. SUBCELLULAR LOCATION: Nucleus .
