NCL proteomics

Question 1

Smpd1

Answer 1

The SMPD1 gene provides instructions for making the enzyme acid sphingomyelinase (ASM), which is responsible for breaking down a fatty substance called sphingomyelin into another lipid called ceramide

Question 2

Gba

Answer 2

GBA stands for glucocerebrosidase. GBA breaks down glucocerebroside, a large molecule in the cell membrane, into glucose and ceramide. When cells die, GBA breaks down glucocerebroside so the components can be reused to form new cells.

Question 3

Asah1

Answer 3

The ASAH1 gene encodes the enzyme acid ceramidase, which breaks down ceramides into sphingosine and fatty acids in lysosomes. Ceramides are involved in many cell functions, including cell growth, differentiation, and apoptosis. Acid ceramidase helps recycle ceramides to create new ones. Acid ceramidase also has a “reverse” enzymatic activity that can synthesize ceramide from sphingosine and fatty acids. The pH at which this synthesis reaction occurs is different from the pH at which the hydrolysis reaction occurs, suggesting that acid ceramidase may have different functions depending on its subcellular location and the local pH.

Question 4

Asah2

Answer 4

The Asah2 gene encodes neutral ceramidase, an enzyme that breaks down ceramide, a second messenger in many cellular events, to produce sphingosine.

Question 5

ceramides

Answer 5

Ceramide, the precursor of all complex sphingolipids, is a potent signaling molecule that mediates key events of cellular pathophysiology. In the nervous system, the sphingolipid metabolism has an important impact. Neurons are polarized cells and their normal functions, such as neuronal connectivity and synaptic transmission, rely on selective trafficking of molecules across plasma membrane. Sphingolipids are abundant on neural cellular membranes and represent potent regulators of brain homeostasis. Ceramide intracellular levels are fine-tuned and alteration of the sphingolipid–ceramide profile contributes to the development of age-related, neurological and neuroinflammatory diseases. The purpose of this review is to guide the reader towards a better understanding of the sphingolipid–ceramide pathway system. First, ceramide biology is presented including structure, physical properties and metabolism. Second, we describe the function of ceramide as a lipid second messenger in cell physiology. Finally, we highlight the relevance of sphingolipids and ceramide in the progression of different neurodegenerative diseases.

Question 6

Gpld1

Answer 6

Glycosylphosphatidylinositol‐specific phospholipase D1 (GPLD1) hydrolyzes inositol phosphate linkages in proteins anchored to the cell membrane. Mice overexpressing GPLD1 show enhanced neurogenesis and cognition.

Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is an enzyme that performs several biological functions, including:
Hydrolyzing GPI-anchored proteins
GPLD1 cleaves the inositol phosphate linkages in proteins that are anchored to the cell membrane. This releases the anchored proteins into the extracellular environment.
Regulating chronic diseases
GPLD1 is involved in the pathogenesis of many chronic diseases, including metabolic diseases, cancer, and neurological disorders.
Improving cognitive impairment
Exercise can increase GPLD1 expression, which can help with cognitive impairment and glucose metabolism in type 2 diabetes. GPLD1 levels can also be increased without exercise to improve cognitive impairment.
Releasing mucous barrier
GPLD1 releases a protective mucous barrier from the oral mucosa.
GPLD1 is primarily secreted by the liver and is abundant in serum.

Question 7

Ppt1

Answer 7

Palmitoyl-protein thioesterase 1 (PPT1) is an enzyme that removes fatty acids from proteins in lysosomes, which are compartments within cells that break down molecules:
Protein breakdown: PPT1 removes long-chain fatty acids, like palmitate, from proteins, which helps break them down when they are no longer needed.
Developmental biology: PPT1 is required for the development of neurons and the function of synapses, which are the connections between nerve cells.
Autophagy: PPT1 depalmitoylates proteins in lysosomes before they are degraded.
Muscle differentiation: PPT1 plays a critical role in the differentiation of skeletal myoblasts.
Tumor growth: PPT1 promotes tumor growth and is a molecular target of chloroquine derivatives in cancer.

Question 8

Ppt2

Answer 8

The palmitoyl protein thioesterase-2 (PPT2) protein is a lysosomal enzyme that removes thioester-linked fatty acyl groups from various substrates:
Cell metabolism: PPT2 is involved in cell metabolism by cutting the thioester linkage between a fatty acid and cysteine in lipid-modified proteins.
Lysosomal thioester catabolism: PPT2 targets lysosomes through the mannose 6-phosphate receptor pathway and has strong activity against palmitoylated model substrates.
Fatty acid chain length specificity: PPT2 hydrolyzes very-long chain fatty acids more efficiently than PPT1.

Question 9

Pld4

Answer 9

Phospholipase D4 (PLD4) is a transmembrane glycoprotein that has multiple functions, including:
Regulating kidney fibrosis: PLD4 is upregulated in mouse models of kidney fibrosis and in biopsy samples from patients with tubulointerstitial fibrosis. Targeting PLD4 could be a novel therapeutic strategy to reverse kidney fibrosis.
Digesting single-stranded DNA: PLD4 is a 5’->3’ DNA exonuclease that digests single-stranded DNA (ssDNA).
Regulating inflammatory cytokine responses: PLD4 regulates inflammatory cytokine responses by degrading nucleic acids.
Involved in phagocytosis: PLD4 is involved in the phagocytosis of microglia in the central nervous system (CNS).
Influencing myelination: PLD4-deficient mice have a mild but significant delay in myelination in the cerebellum and corpus callosum.
Synthesizing S,S-BMP: PLD4 synthesizes S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes.

Question 10

Vdac1

Answer 10

Voltage-dependent anion channel 1 (VDAC1) is a protein that regulates the flow of ions, metabolites, and other substances across the outer mitochondrial membrane:
Mitochondrial function
VDAC1 is a key regulator of mitochondrial function, including metabolism, energy sources, and apoptosis.
Cell life and death
VDAC1 plays a role in cell life and death by regulating the release of apoptotic proteins from the mitochondria.
Mitochondrial gatekeeper
VDAC1 acts as a mitochondrial gatekeeper, interacting with over 100 proteins and orchestrating the interaction between mitochondrial and cellular activities.
Inflammation
VDAC1 can regulate mitochondrial function by interacting with organelles that have Ca2+ channels. Ca2+ plays an important role in the inflammatory response, so VDAC1 may be a potential target for treating inflammation.
Cancer
VDAC1 is highly expressed in tumors, and silencing VDAC1 expression can inhibit the growth of cancer cells and tumors.
VDAC1 is involved in a number of processes, including: Maintaining retinal morphology, Regulating autophagy, and Participating in endoplasmic reticulum (ER)-mitochondria cross-talk.

Question 11

Pitpnc1

Answer 11

This gene encodes a member of the phosphatidylinositol transfer protein family. The encoded cytoplasmic protein plays a role in multiple processes including cell signaling and lipid metabolism by facilitating the transfer of phosphatidylinositol between membrane compartments. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 1.
[Isoform 1]: Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes (PubMed:10531358, 22822086). Binds PA derived from the phospholipase D signaling pathway and among the cellular PA species, preferably binds to the C16:0/16:1 and C16:1/18:1 PA species (PubMed:22822086). ( PITC1_HUMAN,Q9UKF7 )
[Isoform 2]: Catalyzes the transfer of phosphatidylinositol between membranes. ( PITC1_HUMAN,Q9UKF7 )

Question 12

Ubap2l

Answer 12

Ubiquitin-associated protein 2-like (UBAP2L) is a protein that performs many functions, including:
Stress granule assembly
UBAP2L is a key protein in the assembly of stress granules (SGs), which are non-membranous structures that help cells survive under stress. UBAP2L associates with other proteins, such as G3BP1, Caprin1, FXR1/2, and FMRP, to form SGs.
Nuclear pore complex homeostasis
UBAP2L helps maintain the homeostasis of nuclear pore complexes at the nuclear envelope.
RNA polymerase II ubiquitylation
UBAP2L is involved in the ubiquitylation and degradation of RNA polymerase II (RNAPII) after UV irradiation.
Oncogenic role
UBAP2L plays a role in the growth and metastasis of cancer cells, particularly in gastric, breast, and hepatocellular carcinoma (HCC). UBAP2L may regulate the PI3K/Akt and P53 signaling pathways, which are commonly dysregulated in cancerous cells.
Processing body (PB) formation
UBAP2L contributes to the formation of PBs, and can nucleate hybrid granules that contain both SG and PB components.

Question 13

Ttyh2/Ttyh3

Answer 13

TTYHs have been reported to form Ca2+- and cell volume-regulated anion channels structurally distinct from any characterized protein family with potential roles in cell adhesion, migration, and developmental signaling. In the presence of Ca2+, TTYH2 and TTYH3 form homomeric cis-dimers bridged by extracellularly coordinated Ca2+. Strikingly, in the absence of Ca2+, TTYH2 forms trans-dimers that span opposing membranes across a ~130 Å intermembrane space as well as a monomeric state. All TTYH structures lack ion conducting pathways and we do not observe TTYH2-dependent channel activity in cells. We conclude TTYHs are not pore forming subunits of anion channels and their function may involve Ca2+-dependent changes in quaternary structure, interactions with hydrophobic molecules near the extracellular membrane surface, and/or association with additional protein partners.

Question 14

Ppap2b

Answer 14

PPAP2B, also known as Lipid Phosphate Phosphatase 3 (LPP3), is a protein that performs a number of functions, including:
Maintaining vascular integrity
PPAP2B helps maintain the integrity of the endothelial monolayer, which is the lining of blood vessels.
Promoting anti-inflammatory phenotype
PPAP2B helps promote an anti-inflammatory phenotype in response to atherorelevant flows.
Inhibiting LPA receptor-mediated signaling
PPAP2B suppresses signaling mediated by LPA receptors, which are associated with the activation of blood and vascular cells, as well as epithelial cell proliferation and migration.
Converting phosphatidic acid to diacylglycerol
PPAP2B catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DG).
Hydrolyzing lysophosphatidic acid
PPAP2B actively hydrolyzes extracellular lysophosphatidic acid (LPA).
Associated with Wnt signaling
PPAP2B is associated with Wnt signaling, which is important for the proper formation of tissues like the heart, bone, and muscle during embryonic development.

Question 15

CLN3/5:

Question 16

Wdfy1

Answer 16

WDFY1 (WD Repeat And FYVE Domain Containing 1) is a protein that plays a role in several processes, including:
Immune response: WDFY1 is an adaptor protein that strengthens the interaction between TLR3 and TLR4, and the adaptor TRIF. This interaction is important for the innate immune response, and for the production of inflammatory cytokines and type I interferons.
Endocytic trafficking: WDFY1 is involved in endocytic trafficking and autophagy. Overexpression of WDFY1 can lead to defective endocytic trafficking and autophagy.
Hematopoietic stem cells: WDFY1 may play a role in maintaining hematopoietic stem cells.
Schizophrenia: WDFY1 protein levels are upregulated in the brain of patients with schizophrenia.
Ciliogenesis: WDFY1 is essential for normal ciliogenesis.

Endosomal membrane protein WDFY1 interacts with both Toll‐like receptors and recruits the adaptor TRIF, enabling downstream signaling. WDFY1 potentiates IRF3 and NF‐kB activation, as well as type I IFN and inflammatory cytokine production in response to poly(I:C) and LPS.

Question 17

Class switch recombination (CSR)

Answer 17

Class switch recombination (CSR) is a DNA process that changes the type of antibody a B cell produces:
Explanation
CSR allows B cells to switch from producing one type of antibody, like IgM, to producing another, like IgG, IgE, or IgA. The new antibody is better able to protect against the pathogen.
Process
CSR involves the activation of enzymes that create DNA double-strand breaks in the Ig heavy chain locus. These breaks lead to the recombination of the variable heavy-chain (VDJ) segment with a different constant heavy (CH) chain gene.
Regulation
B cells use a complex regulatory framework to ensure that the DNA breaks are repaired productively, and not in a way that could lead to lymphoma.
Significance
CSR is important to understand because dysregulation can lead to self-reactive BCRs and B cell lymphomas. Patients with class-switch recombination deficiency (CSR-D) often have recurrent bacterial infections.

Question 18

Igh-3

Answer 18

The 3′ regulatory region (3′RR) of the immunoglobulin heavy chain (IgH) cluster controls a number of functions, including:
Class switch recombination (CSR): The 3′RR modulates CSR by enhancing the transcription of C(H) genes. However, the 3′RR is not essential for CSR, and deleting it in a mouse B cell line only slightly reduces CSR.
IgH expression: The 3′RR is required for high levels of IgH expression in plasma cells.
B cell maturation: The 3′RR plays a role in B cell maturation in mammals.
Autoimmune diseases: The 3′RR1 hs1.2 enhancer is associated with autoimmune diseases.
The 3′RR is located downstream of the C(H) locus and is about 28 kb long. The 3′RR’s effects are largely mediated by activating specific epigenetic marks in the DNA it targets. This suggests that targeting the 3′RR could be a potential strategy for treating mature B-cell lymphomas.

Question 19

Ighg1

Answer 19

IGHG1, the gene that encodes immunoglobulin heavy constant gamma 1 (IgG1), is associated with several processes in the brain and nervous system, including:
Glioma progression
IGHG1 expression is higher in gliomas and molecular subtypes with a poor prognosis. Patients with high IGHG1 expression have worse overall survival.
Huntington’s disease
IGHG1 is associated with Huntington’s disease, a chronic, inherited neurodegenerative disorder.
Multiple sclerosis
IgG1 glycosylation patterns are altered in the cerebrospinal fluid (CSF) of multiple sclerosis patients.
B-cell maturation
In multiple sclerosis, there is an enhanced B cell-to-ASC transition in distinct CNS compartments.
IGHG1 is also predicted to enable antigen binding activity and immunoglobulin receptor binding activity. It is involved in several processes, including: Activation of immune response, Defense response to other organisms, and Phagocytosis.

Question 20

Glb1

Answer 20

β-Galactosidase (GLB1) catalyzes the degradation of galactosylceramide to galactose and ceramide within the lysosome. It also displays activity against galactosylsphingosine and lactosylceramide.

Question 21

Mesdc2

Answer 21

Mesoderm development candidate 2 (MESDC2) is a protein that plays a key role in the formation of the neuromuscular junction (MNJ) and the cell-surface expression of LRP4:
Binds to LRP4: MESDC2 binds to LRP4 and facilitates its glycosylation.
Regulates LRP4 surface expression: MESDC2 regulates the surface expression of LRP4 in myotubes.
Activates MuSK: MESDC2 activates MuSK.
Promotes postsynaptic specialization: MESDC2 promotes postsynaptic specialization in cultured myotubes.
MESDC2 is also a chaperone for the low-density lipoprotein receptor (LDLR) family in the endoplasmic reticulum (ER). It binds to the Wnt co-receptors LRP5 and LRP6, and is required for their proper folding and cell surface expression.

Question 22

Gorasp2

Answer 22

In lysosomes, GORASP2 (Golgi reassembly stacking protein 2) helps with autophagosome-lysosome fusion, autophagosome maturation, and phagophore closure:
Autophagosome-lysosome fusion: GORASP2 acts as a membrane tether that connects autophagosomes and lysosomes by binding to LC3 on autophagosomes and LAMP2 on lysosomes.
Autophagosome maturation: GORASP2 helps assemble the PtdIns3K UVRAG complex at the interface of autophagosomes and lysosomes.
Phagophore closure: GORASP2 promotes phagophore closure.
GORASP2 is a key structural protein in the Golgi apparatus. It helps stack Golgi cisternae and form the Golgi ribbon. GORASP2 also plays a role in the intracellular transport of transforming growth factor alpha.

Question 23

Ergic2

(in cln3/grn)

Answer 23

the COPII-associated proteins ERGIC2 (ER-Golgi intermediate compartment) and ERGIC3 are specifically required for the efficient intracellular transport of gap junction proteins in both Caenorhabditis elegans and mice. In the absence of Ergic2 or Ergic3, gap junction proteins accumulate in the ER and Golgi apparatus and the size of endogenous gap junction plaques is reduced. Knocking out the Ergic2 or Ergic3 in mice results in heart enlargement and cardiac malfunction accompanied by reduced number and size of connexin 43 (Cx43) gap junctions.

The biological function of ERGIC2 is unknown, but it’s believed to be a chaperon molecule that helps transport proteins between the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi. ERGIC2 and ERGIC3 also regulate the transport of gap junction proteins from the ER to the Golgi.
The endoplasmic reticulum (ER) and lysosomes interact in a number of ways, including:
ER-phagy
A series of processes that lead to the lysosomal turnover of parts of the ER. ER-phagy is important for cell and organism life, and mutations in genes involved in ER-phagy can cause neurological disorders and cancers.
ER-lysosome contacts
These contacts allow for the transfer of calcium between the ER and lysosomes, which can help replenish lysosomal calcium stores.
ER stress
ER stress can cause lysosomes to de-acidify, increase in size, and become more permeable. It can also inhibit autophagic flux.

Question 24

Hmga1

Answer 24

High Mobility Group A1 (HMGA1) is a protein that regulates gene expression, chromatin remodeling, and immune responses. It’s involved in many cellular processes, including inflammation, proliferation, and DNA repair. HMGA1 is also implicated in tumorigenesis and cancer progression.

High mobility group A1 (HMGA1) is a nonhistone chromatin structural protein characterized by no transcriptional activity. It mainly plays a regulatory role by modifying the structure of DNA. A large number of studies have confirmed that HMGA1 regulates genes related to tumours in the reproductive system, digestive system, urinary system and haematopoietic system. HMGA1 is rare in adult cells and increases in highly proliferative cells such as embryos. After being stimulated by external factors, it will produce effects through the Wnt/β-catenin, PI3K/Akt, Hippo and MEK/ERK pathways. In addition, HMGA1 also affects the ageing, apoptosis, autophagy and chemotherapy resistance of cancer cells, which are linked to tumorigenesis.

Question 25

Psat1

Answer 25

Phosphoserine aminotransferase 1 (PSAT1) is an enzyme that plays a role in many processes, including: Cancer: PSAT1 is an oncogene that can promote the growth and spread of cancer cells. It's overexpressed in many types of tumors, including breast cancer, lung cancer, and ovarian cancer. PSAT1 can help cancer cells resist drugs and spread to other parts of the body. Serine and α-ketoglutarate production: PSAT1 is a key enzyme in the production of these two metabolites, which are involved in carbon metabolism and the tricarboxylic acid cycle. Collagen production: PSAT1 is required for lung fibroblasts to produce collagen protein. Mental diseases and developmental abnormalities: Mutations in the PSAT1 gene can lead to these conditions. Insulin sensitivity: Hepatic PSAT1 regulates insulin sensitivity in mice. Dental pulp stem cell aging: The serine metabolic pathway that PSAT1 is involved in can affect the aging of dental pulp stem cells. PSAT1 is a class V aminotransferase and a rate-limiting enzyme in the serine-glycine synthesis pathway.

Question 25

Ergic1

Answer 25

The ERGIC1 protein, or endoplasmic reticulum-golgi intermediate compartment 1 protein, has multiple functions, including: Stabilizing the ERGIC2/ERGIC3 complex ERGIC1 is a membrane-bound protein in the ER and Golgi that stabilizes the ERGIC2/ERGIC3 complex. Regulating ER–Golgi trafficking The ERGIC regulates ER–Golgi trafficking, which is essential for conventional secretion. Increasing the turnover of other ERGIC proteins ERGIC1 interacts with other ERGIC proteins to increase their turnover. Forming 5-taurinomethyl-2-thiouridine ERGIC1 is required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln).

Question 25

Jup

Answer 25

The JUP gene produces the protein plakoglobin, which helps hold cells together in tissues and plays a role in signaling within cells: Cell structure Plakoglobin is a component of desmosomes and adherens junctions, which are specialized structures that help cells stick together. Cell signaling Plakoglobin may be involved in Wnt signaling, which controls gene activity and cell interactions. Wnt signaling is important for the development of the heart, skin, and hair. Cell viability Plakoglobin is a key regulator of cell-cell contact, which may be a fundamental control mechanism for cell viability. Tumor progression JUP expression may be associated with tumor malignancy. For example, in gastric cancer, JUP expression decreases as the cancer becomes more malignant. High JUP expression is also associated with adverse tumor features, such as advanced tumor stage and lymph node metastases. Cardiac muscle Plakoglobin is located in the intercalated discs of cardiac muscle, where it helps anchor sarcomeres and join adjacent cells. Mutations in plakoglobin are associated with arrhythmogenic right ventricular dysplasia.

Question 26

Man2b2

Answer 26

MAN2B2, or Mannosidase Alpha Class 2B Member 2, is a protein that breaks down glycoproteins in lysosomes. It's a member of the mannosidase gene family, which is involved in the catabolism of glycoproteins and regulating glycosylation homeostasis. MAN2B2's specific function is to cleave the α-1,6-mannose residue and Man2GlcNAc1, which generates free monosaccharides. These monosaccharides are then recycled for glycan synthesis.

Question 27

Fam49b

Answer 27

FAM49B, or Family with sequence similarity 49 member B, is a protein that plays a number of roles in the body, including: Regulating mitochondrial function FAM49B regulates mitochondrial fission and fusion, and acts as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Regulating the immune system FAM49B suppresses T cell activation by regulating the TCR signal transduction via modulating the actin cytoskeleton. Regulating the tumor immune microenvironment FAM49B may play a key role in regulating the tumor immune microenvironment and anti-tumor drug tolerance. Promoting cancer proliferation FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance. Regulating thymocyte development FAM49b dampens thymocytes TCR signaling to ensure normal thymocyte development and peripheral T cells survival. Restricting bacterial infection FAM49B reduces the entry of several intracellular bacterial pathogens into both phagocytic and non-phagocytic host cells. FAM49B is also known as CYRI-B, which stands for CYFIP-related Rac1 interactor.

Question 28

Hdgfrp2

Answer 28

Hepatoma-derived growth factor-related protein 2 (HDGFRP2), also known as HRP-2, promotes DNA repair and is essential for the survival of certain cells: DNA repair: HDGFRP2 promotes DNA repair by homologous recombination, which is a process that repairs DNA double-strand breaks. Cellular growth control: HDGFRP2 is involved in regulating cyclin D1 expression, which helps control cellular growth. Cell survival: HDGFRP2 is essential for the survival of U2OS and HeLa cells

Question 29

Trim3

Answer 29

Trafficking of TLR3 from the ER to endolysosomes and its subsequent proteolytic cleavage are necessary for it to sense viral dsRNA and trigger antiviral response. Understanding how TLR3 trafficking is regulated is important for deciphering the mechanism of TLR3-mediated innate immune and inflammatory responses. In this study, we report that TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831. Subsequently, the polyubiquitinated TLR3 is recognized and sorted by the ESCRT complexes to endolysosomes to promote the activation of downstream signaling. This study provides insights into how the trafficking and activation of TLR3 are regulated for efficient innate immune response to extracellular and endosomal viral dsRNA. The understanding of ubiquitin E3 ligase function hinges on thoroughly identifying their cellular targets, but the transient nature of signaling complexes leading to ubiquitination poses a significant challenge for detailed mechanistic studies. TRIM2 and TRIM3 are paralogous mammalian E3 ligases with particularly high expression in the brain, where they contribute to neuronal development and homeostasis. Here, we tailored recently developed ubiquitin-specific proximity labelling tools to identify substrates of TRIM2 and TRIM3 activity.

Question 30

Zfpl1

Answer 30

Zinc finger protein like 1 (ZFPL1) is a protein that plays a role in the following processes: Maintaining cis-Golgi integrity ZFPL1 is an integral membrane protein that interacts with GM130 to maintain the structure and function of the cis-Golgi. Regulating autophagy ZFPL1 may play a role in regulating autophagy in cells like NCIN87 and BGC823. Knockdown of ZFPL1 can induce cell death through autophagy.

Question 31

Nrip3

Answer 31

Two aspartic proteases significantly increased in expression in OA are nuclear hormone interacting proteins (NRIP2 and NRIP3). These proteases are recently discovered and have not been reported in cartilage before, but nuclear hormone receptors have many roles in cartilage homeostasis. Accelerates RTF2 removal: NRIP3 binds to and increases DDI1 and RTF2, which accelerates the removal of RTF2. RTF2 is a key factor in a cell's ability to manage replication stress. Increases DDI1 expression: NRIP3 increases DDI1 expression through PPARα. Inhibits PI3K-AKT signaling: NRIP3 suppresses colorectal cancer (CRC) growth by inhibiting PI3K-AKT signaling.

Question 32

Slc33a1

Answer 32

SLC33A1, also known as AT-1, is a protein that performs a variety of functions, including: Acetyl-CoA transport SLC33A1 transports acetyl-CoA from the cytosol into the endoplasmic reticulum (ER) lumen. Acetyl-CoA is used as an acetyl-group donor for Nε-lysine acetylation. Autophagy induction SLC33A1 regulates the induction of autophagy downstream of the IRE1/XBP1 pathway. Solute: proton symporter activity SLC33A1 participates in transmembrane transport and SMAD protein signal transduction. BMP signaling SLC33A1 can negatively regulate BMP signaling.

Question 33

Dnajc10

Answer 33

This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins.

Question 34

Man1a2

Answer 34

Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. The MAN1A2 gene, or mannosidase alpha class 1A member 2, is a protein coding gene that performs a number of functions, including: Mannosyl-oligosaccharide 1,2-alpha-mannosidase activity: MAN1A2 is involved in the maturation of Asn-linked oligosaccharides. Calcium ion binding: MAN1A2 binds calcium ions. Hydrolase activity: MAN1A2 acts on glycosyl bonds. Metal ion binding: MAN1A2 binds metal ions. MAN1A2 is associated with diseases such as Rafiq Syndrome and Visual Epilepsy. It is also involved in the Endoplasmic Reticulum-associated degradation pathway.

Question 35

Ctsd

Answer 35

Cathepsin D (CTSD) is a protein that performs many functions in the body, including: Protein degradation: CTSD breaks down misfolded, mutated, and long-lived proteins. It also degrades disease-associated proteins like amyloid precursor protein (APP), tau, and α-synuclein. Cell signaling: CTSD regulates the activity of enzymes, polypeptides, and growth factors, which is important for cell signaling. Cell death: CTSD regulates cell death, and is involved in some models of apoptosis. Inflammation: CTSD activates inflammatory cells. Cancer: CTSD is overexpressed in many cancers, and is involved in cancer invasion, metastasis, and angiogenesis. Neurodegenerative disorders: Genetic variants in the CTSD gene have been linked to neurodegenerative diseases like Alzheimer's disease and Parkinson's disease.

Question 36

Kcnc3

Answer 36

KCNC3, also known as the human Kv3.3 gene, is a voltage-gated potassium channel protein that plays a role in a variety of functions, including: Potassium ion transport: KCNC3 is involved in the transport of potassium ions. Ion transmembrane transport regulation: KCNC3 regulates the transport of ions across the membrane.

Question 37

Uso1

Answer 37

USO1 (also known as p115/TAP) is a protein that plays a critical role in the transport of vesicles from the endoplasmic reticulum (ER) to the Golgi apparatus: Vesicle transport USO1 tethers vesicles in the ER-Golgi complex, which is essential for vesicular trafficking and transport during interphase. Mitosis and apoptosis USO1 plays a critical role in both mitosis and apoptosis. Mitotic spindle function USO1 is essential for mitotic spindle function through interacting with γ-tubulin. Protein transport USO1 is required for normal protein transport from the ER to the Golgi apparatus and the cell membrane.

Question 38

Arsa

Answer 38

Arylsulfatase A (ARSA) is an enzyme that helps process sulfatides, a type of fat that's a key component of cell membranes. ARSA is located in lysosomes, the cell's recycling centers, and is responsible for breaking down sulfatides into cerebroside and sulfate. ARSA is important because sulfatides are abundant in the white matter of the nervous system, which insulates and protects nerves. A deficiency in ARSA results in metachromatic leukodystrophy (MLD), a lysosomal storage disease that causes severe and progressive neurological symptoms.

Question 39

Slc17a6

Answer 39

SLC17A6, also known as the vesicular glutamate transporter 2 (VGLUT2), is responsible for a number of functions, including: Neurotransmitter transport: SLC17A6 is involved in the transport of neurotransmitters and L-glutamate across membranes. Synaptic transmission: SLC17A6 is involved in glutamatergic synaptic transmission. Synapse structure and activity: SLC17A6 helps regulate synapse structure and activity. Neurotransmitter loading: SLC17A6 helps load neurotransmitters into synaptic vesicles. Retinal hyaloid vessel regression: SLC17A6 is involved in regulating the regression of retinal hyaloid vessels during postnatal development. Chloride channel: SLC17A6 acts as a chloride channel, which allows chloride to pass through the synaptic vesicle membrane. Vesicular K+/H+ antiport: SLC17A6 helps maintain the electrical gradient and decrease the chemical gradient, which helps sustain vesicular glutamate uptake. Symporter: SLC17A6 functions as a symporter at the plasma membrane, allowing for the regulation of synaptic phosphate homeostasis.

Question 40

Galns

Answer 40

The GALNS gene provides instructions for producing the lysosomal enzyme N-acetylgalactosamine 6-sulfatase, which breaks down large sugar molecules called glycosaminoglycans (GAGs): Function GALNS removes a sulfate group from GAGs like keratan sulfate and chondroitin 6-sulfate. Deficiencies Mutations in the GALNS gene can lead to a deficiency in the enzyme, which can cause Morquio A syndrome, a lysosomal storage disorder. Treatments GALNS replacements can help reduce the buildup of GAGs in bone and cartilage, which may slow the progression of skeletal abnormalities. GALNS is also known as N-acetylgalactosamine-6-sulfatase and GalN6S.

Question 41

Grm3

Answer 41

Glutamate receptor, metabotropic 3 (GRM3) is a gene that encodes a protein that functions in inhibition of the cyclic AMP cascade. The metabotropic glutamate receptors (mGluR) modulate glutamatergic signaling and also influence the release of other neurotransmitters such as dopamine and GABA. mGluR are implicated in synaptic plasticity, cognition, and arousal. Strengthening synaptic connectivity In higher cortical circuits in primates, mGluR3 is localized post-synaptically, where it strengthens synaptic connectivity. Increasing glial glutamate uptake mGluR3 on PAPs increases glial glutamate uptake by increasing EAAT expression.

Question 42

Epdr1

Answer 42

Ependymin-related protein 1 (EPDR1) is a protein that plays a role in a number of processes, including: Regulating β-cell metabolism EPDR1 positively regulates insulin secretion in pancreatic islets and β-cell lines. It also promotes the coupling of glycolysis to the mitochondrial TCA cycle. Promoting tumor immune evasion EPDR1 promotes CD8+ T-cell exhaustion by elevating the transcriptional level of PD-L1. Regulating angiogenesis EPDR1 is a major Smad1/5 gene target induced by insulin, which stimulates angiogenesis in blood vessels. Related to calcium-dependent cell adhesion EPDR1 is a type II transmembrane protein related to calcium-dependent cell adhesion.

Question 43

Wars2

Answer 43

The WARS2 protein, or tryptophanyl-tRNA synthetase 2, is a mitochondrial protein that performs a number of functions, including: Protein synthesis WARS2 is a vital part of the translation process, which is involved in protein synthesis. Angiogenesis WARS2 is a pro-angiogenic factor that regulates capillary density in the heart. Neurological disorders WARS2 is associated with a number of neurological disorders, including mitochondrial neurodevelopmental disorder, Parkinsonism-Dystonia 3, and early-onset tremor-parkinsonism syndromes. Pseudorabies virus infection WARS2 facilitates pseudorabies virus (PRV) infection by managing protein and lipid levels. WARS2 is one of 14 mitochondrial aminoacyl-tRNA synthetases that are linked to neurological disorders. It is expressed in many tissues, including the kidney and colon.

Question 44

Mylk

Answer 44

Myosin light chain kinase (MYLK) protein is a calcium/calmodulin-dependent enzyme that plays a role in many cellular functions, including: Smooth muscle contraction: MYLK phosphorylates myosin light chains, which initiates contraction in smooth muscle cells. Cell motility and morphology: MYLK is involved in cell motility and morphology. Inflammatory response: MYLK is involved in the inflammatory response, including apoptosis, vascular permeability, and leukocyte diapedesis

Question 45

Tmed2

Answer 45

TMED2, a cargo receptor protein, helps assemble the cargo protein MITA into the COP II complex by strengthening the interaction between MITA and Sec24C: Role TMED2 recruits MITA to the COP II complex, which is critical for MITA-mediated IFN signaling. Family TMED2 is a member of the p24 family of cargo receptors, which have dihydrophobic ER-export motifs. Function TMED2 is involved in vesicle trafficking and protein secretion. It also interacts with both endosomal and membrane TLRs, including TLR2, TLR4, and TLR3. TMED2 is a Golgi protein that also modulates HH signaling.