Transporters, Receptors, and other vocab

Question 1

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

GLUT4

Answer 1

Glucose transporter 4. Found in skeletal muscle. Insulin dependent.

Question 2

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

MuRF1

Answer 2

Muscle ring finger protein-1, an E3 ubiquitin ligase

Cortisol indirectly upregulates MuRF1 to increase proteolysis

(From Dr. Pak: In diseases that suppress insulin/IGF-1 signaling, the PI3-K/Akt pathway is depressed, leading to decreased protein synthesis and FoxO phosphorylation. This allows FoxO to stimulate the expression of the E3 enzymes atrogin-1 and muscle ring finger-1 (MuRF-1) and protein degradation.)

Question 3

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

NF-KB

Answer 3

Transcription factor for a number of inflammatory genes; exists constitutively in the cytosol bound to its inhibitor, I-KB (glucocorticoids bind/inactivate NF-KB; up regulate I-KB)

Question 4

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

11-DOC

Answer 4

11-Deoxycorticosterone. Mineralocorticoid precursor of aldosterone. If in excess (for example if missing an enzyme further into the pathway), may bind MR receptors producing the same physiological effects as aldosterone - sodium/water retention, probably also HTN

Question 5

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

11ß-HSD1

Answer 5

11-ß hydroxysteroid dehydrogenase 1; present in cells with glucocorticoid receptors, converts cortisone to cortisol (active form)

Question 6

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

11ß-HSD2

Answer 6

11ß hydroxysteroid dehydrogenase 2. In cells with mineralocorticoid receptors (especially kidney distal convoluted tubule), converts cortisol to cortisone (inactive; freely diffuses out of the cell)

Question 7

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

DHEA

Answer 7

5-dehydroepiandrosterone. Weak androgen produced by adrenal zona reticularis; precursor for testosterone/E2.

Question 8

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

StAR

Answer 8

Steroid Acute Regulatory Protein. Transports free cholesterol from outer mitochondrial membrane to inner mitochondrial membrane. RATE LIMITING STEP FOR STEROID BIOSYNTHESIS. Regulated by ACTH

Question 9

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Cyp11A1

Answer 9

Cyp11A1 is the gene coding for P450scc, or desmolase. Desmolase converts cholesterol to pregnenolone, the primary precursor for all steroid hormones, by cleaving off a side chain of cholesterol (activity increased as ACTH levels increase). Expressed in inner mitochondrial membrane of all three layers of adrenal cortex.

Question 10

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CYP21A2

Answer 10

P450c21; 21α hydroxylase. Expressed in adrenal cortex zona glomerulosa and fasciculata

Converts progesterone to 11-deoxycorticosterone (11-DOC) in z. glomerulosa

Converts 17(OH)-progesterone to 11-deoxycortisol in z. fasciculata

Question 11

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CYP11B2

(one gene product with three activities; give common name of gene product as well as common name of each activity)

Answer 11

P450aldo; Aldosterone synthase. Present in Zona glomerulosa of adrenal cortex

(do not confuse with CYP11B1 gene product, which functions in the cortisol biosynthetic pathway)

1. 11-hydroxylase converts 11-DOC to corticosterone.
2. 18-hydroxylase converts corticosterone to 18(OH)-corticosterone.
3. 18-oxidase converts 18(OH)-corticosterone.to aldosterone (NOT cortisol!)

Question 12

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CYP17

Answer 12

P450c17; 17-hydroxylase. Present in zona fasciculata and reticularis of adrenal medulla.

Converts progesterone to 17(OH)-progesterone in cortisol biosynthetic pathway in z. fasciculata

Converts pregnenolone to 17(OH)-pregnenolone in DHEA biosynthetic pathway in z. reticularis

Question 13

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CYP11B1

Answer 13

P450c11; 11-hydroxylase

not to be confused with a gene product of the same common names, CYP11B2/aldosterone synthase!

Converts 11-deoxycortisol (NOT 11-DOC) to cortisol in cortisol biosynthetic pathway. Expressed in zona fasciculata.

Question 14

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

COMT

Answer 14

catechol-O-methyltransferase

Methylates catecholamines for clearance.

End product of breakdown: vanyllilmandelic acid

Question 15

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

MAO

Answer 15

monoamine oxidase

Deaminates catecholamines for clearance

Eventual end product: vanillylmendelic acid

Question 16

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

NIS

Answer 16

Sodium-iodide symporter. Found on basolateral membrane of thyroid follicular epithelial cell. Together with thyroid peroxidase (TPO; forms iodine), thyroid iodide “trap”

Question 17

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Type I deiodinase

Answer 17

Outer and inner ring deiodinase.

Found in liver, kidney, skeletal muscle, thyroid

Primary source of T3 in circulation

Question 18

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Type II deiodinase

Answer 18

Outer ring deiodinase only (activates T4 → T3)

Found in brain, pituitary, placenta, cardiac muscle

**Also the thyroid “sensor” in the pituitary

Question 19

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Type III deiodinase

Answer 19

Inner ring deiodinase only (inactivating enzyme)

Found in brain, placenta, skin

Question 20

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

TBG

Answer 20

Thyroid binding globulin. Carries 70% of T4/T3 in circulation

394aa glycoprotein; Serpin family (but not a protease inhibitor)

Circulating protein, synthesized in liver

Hepatitis, increased [estrogen] increase TBG; Nephrotic syndrome, steroids decrease TBG; neither affects free T4/T3

**Unique: Reversibly binds T4 (compare to other steroid binding globulins)

Question 21

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

TG

Answer 21

Thyroglobulin

Found exclusively in thyroid; used for T3/T4 synthesis. Stored in colloid and makes up the bulk of colloid mass.

Question 22

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

TTR

Answer 22

Transthyretin. A secondary thyroid binding protein. Transports about 10% of T4/T3 in circulation

Question 23

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

THR

Answer 23

Thyroid hormone receptor

Nuclear receptor

Forms heterodimer with retinoic acid

Question 24

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

PTHrP

Answer 24

Parathyroid hormone related peptide

Highly analagous to N-terminal (active; 1-34) fragment of PTH

Has some normal functions, but most known for calcium wasting from bone / hypercalcemia when secreted to excess by a neoplasm [commonly renal, head/neck, lymphoma, bladder]

Question 25

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

PTH1R

Answer 25

Primary PTH receptor

Located in osteoblasts and kidney

Binds both 1-34 and 1-84 fragment as well as PTHrP

Gs and Gq activity - cAMP AND IP3/DAG

Question 26

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

PTH2R

Answer 26

Secondary parathyroid hormone receptor. Not especially important in humans (that we know of)

Question 27

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

RANKL

Answer 27

RANK - ligand.

Secreted by osteoblasts. Stimulates osteoclasts, promotes bone remodeling.

Inhibited by OPG

Question 28

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

OPG

Answer 28

Osteoprotegerin.

Antagonist/soluble decoy for RANKL (binds and prevents from activating RANK - decreases osteoclast activity

Stimulated by PTH, estrogens; inhibited by cortisol

Question 29

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CYP1α

Answer 29

1α-hydroxylase.

Expressed in renal cells of proximal tubule.

Converts 25-hydroxycholecalciferol (25(OH)-D₃) to active form of Vitamin D: 1,25-dihydroxycholecalciferol (1,25(OH)-D₃)

Question 30

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CaSR

Answer 30

Calcium-sensing Receptor

Located in chief cells, kidney tubules, C cells

Binds ionized calcium; represses PTH at promoter level; stimulates PTH degradation

Question 31

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

VDR

Answer 31

Vitamin D receptor.

Inhibits PTH synthesis at promoter level

Stimulates CaSR gene transcription

Question 32

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

GLUT1

Answer 32

Insulin independent glucose transporter; uptake under basal conditions

Expressed in brain, vasculature, erythrocytes, SkM, fat, heart (minor in heart)

Question 33

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

GLUT2

Answer 33

Insulin independent glucose transporter

LOW AFFINITY

Expressed in liver, pancreatic beta cells, kidney, small intestine

Question 34

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

GLUT3

Answer 34

Glucose transporter

Insulin independent

Primary glucose transporter in brain/neural tissue

Question 35

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

GLUT5

Answer 35

Fructose transporter

Expressed in small intestine, spermatozoa

Question 36

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

IgG

Answer 36

Predominant antibody induced in secondary immune response

Only Ig to cross placenta

Complement fixation variable based on subtype

gamma chain. MW 150 kD

Question 37

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

SReBP-1C

Answer 37

Steroid Regulator Binding Protein 1C

Promotes triglyceride synthesis

Activates glucokinase, promoting glucose “trapping” in cells

Question 38

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

PPARγ

Answer 38

Peroxisome proliferator-activated receptor gamma (or glitazone receptor)

Nuclear transcription factor

Regulates TG storage and adipocyte differentiation

Question 39

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

PAMPS

Answer 39

Pathogen-associated Molecular Patterns

“molecular danger pattern” specific to a pathogen.

Sensed by pattern recognition receptors (TLRs, etc) on innate immune cells

Question 40

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

DAMPS

Answer 40

Damage associated molecular patterns

Recognized by pattern recognition receptors on innate cells (TLRs etc)

Question 41

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

TLR

Answer 41

TOLL-like receptor.

Family of transmembrane pattern recognition receptors (PRR) expressed on phagocytes

Question 42

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

RLR

Answer 42

RIG-I helicase-like receptor

Retinoic acid inducible gene receptor

Family of soluble intracytoplasmic pattern recognition receptors (PRR) expressed by phagocytes

Question 43

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

NLR

Answer 43

NOD-like receptor

Nucleotide binding domain and leucine rich repeating receptor

Family of soluble intracytoplasmic pattern recognition receptors (PRR) expressed by phagocytes

Question 44

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CLR

Answer 44

C-type lectin receptor

Family of transmembrane pattern recognition receptors (PRR) expressed on phagocytes

Question 45

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

IgA

Answer 45

Predominant Ig in external secretions

In secretions, exists primarily as a dimer; circulates as a monomer

Complement fixation by alternative pathway

alpha heavy chain. MW 160 kD

Question 46

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

IgM

Answer 46

Predominant Ab induced in primary response; also expressed as a monomer on B cells (part of BCR)

Low avidity, high affinity (due to 10 epitope binding sites) makes it ideal for a first responder

Effective complement fixation - classical pathway

mu heavy chain. (pentameric) MW 900 kD

Question 47

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

IgD

Answer 47

found on surface of B cells

delta heavy chain

Question 48

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

IgE

Answer 48

primary Ig of allergic reactions

2 Fc receptors on epsilon heavy chain. MW 190 kD

Heavily glycosylated

Binds with very high (20K x IgG) affinity to its FcR

Normal response to parasites

Question 49

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

FcR

Answer 49

Fc receptor

Ig-heavy-chain-subtype-specific-Fc-region receptor found on the surfaces of macrophages, neutrophils, NK cells, eosinophils, basophils, and mast cells.

Cross-linking of receptors activates cells

Question 50

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

atrogin-1

Answer 50

An E3 ubiquitin ligase. Cortisol indirectly upregulates atrogin-1 to increase proteolysis.

(From Dr. Pak: In diseases that suppress insulin/IGF-1 signaling, the PI3-K/Akt pathway is depressed, leading to decreased protein synthesis and FoxO phosphorylation. This allows FoxO to stimulate the expression of the E3 enzymes atrogin-1 and muscle ring finger-1 (MuRF-1) and protein degradation.)

Question 51

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

ITAM

Answer 51

immunoreceptor tyrosine-based activation motif

it’s a motif that exists in the tails of certain receptors of the immune system. [The tyrosine residues of the motif are phosphorylated and form docking sites for other proteins in the signaling cascade]

With regard to the binding of an FcR on a phagocyte, this creates the intracellular signal to phagocytose the antigen

high affinity - activated at low levels of immune complexes

Question 52

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

ITIM

Answer 52

immunoreceptor tyrosine based inhibitory motif

similar to an ITAM, it is a highly conserved aa sequence found on the tails of immune cells. When the receptor binds ligand, the tyrosines are phosphorylated and serve as a docking site for further intracellular signaling proteins

Important regulatory mechanism for B cells - low affinity - activtated when there are very high levels of immune complex to shut off antibody production

Question 53

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

B7

Answer 53

(aka CD80 and CD86)

co-stimulatory molecule expressed on the surface of activated Dendritic cells

interfaces with CD28 on T lymphocytes

major signature of an activated APC that has taken up a microbial pathogen; expressed on BC’s ONLY AFTER uptake of an antigen specific to to its BCR

Question 54

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

TAP (1 and 2)

Answer 54

Transporters Associated with Antigen Processing (1 and 2)

sole function is to push degraded proteins into ER for presentation by MHC-1

Question 55

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

calnexin

Answer 55

ER chaperone

(MHC-I is bound to calnexin until associated with β₂-microglobulin; then passed to calreticulin/ERp57)

Question 56

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

ERp57

Answer 56

ER chaperone

(along with calreticulin, receives MHC-1 after binding of β₂microglobulin)

associates with TAP via tapasin

Question 57

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

calreticulin

Answer 57

ER chaperone

along with ERp57, receives MHC-1 from calnexin after binding of β₂-microglobulin

the complex associates with TAP via tapasin

Question 58

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

ERAAP

Answer 58

endoplasmic reticulum aminopeptidase associated with antigen processing

expressed in ER. trims proteins pumped into ER by TAP, for presentation on MHC-I

Question 59

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

tapasin

Answer 59

ER protein

associates TAP with the calreticulin/ERp57/MHC-I complex for peptide delivery

Question 60

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Ii

Answer 60

invariant chain

MHC-II are transported from ER to endosomes with Ii occupying the peptide cleft

Ii cleaved by acidification leaving CLIP

Question 61

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CLIP

Answer 61

class II-associated invariant chain peptide

remnant of Ii that remains in MHC-II binding groove after acidification of storage endosome

thought to be the only thing expressed in MHC-II cleft under steady state conditions

HLA-DM causes dissociation and allows other peptides to bind

Question 62

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

HLA-DM

Answer 62

binds MHC-II-CLIP complex in endosome and releases CLIP, allowing antigenic peptides to find binding cleft

Question 63

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CD28

Answer 63

costimulatory molecule expressed on naive TC’s

complex with B7 on APC to activate cell

(secondary signal to antigen/MHC-II recognition - and remember, these naive T’s are recognizing MHC-II, so whatever subset they evolve into, they are already CD3⁺/CD4⁺)

Question 64

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CD40

Answer 64

expressed on APC’s that have taken up “something weird” that isn’t a microbe - instead of B7

interfaces with CD40L on CD4’s to induce expression of B7 on the APC, which can then interface with CD28)

(extra step in the activation of the T cell)

Question 65

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CD40L

Answer 65

expressed on the surface of TC’s that recognize “something” in an MHC-II of an APC (but the APC lacks B7 because the “something” isn’t a microbe)

interfaces with CD40 on the APC if the APC thinks it’s “weird” too

CD40/CD40L interaction stimulates the production of B7 which provides the costimulatory signal to the T cell

Question 66

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

CD34

Answer 66

marker for HSC’s

Question 67

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

Notch

Answer 67

receptor expressed on HSC’s in thymus

DL-1/4 binding (Notch Signaling) from TEC’s (DL=delta ligand) commits the cell to T/NK lineage

if notch signaling continues long enough, HSC commits to NK lineage

Question 68

Give the common name of the protein or gene product, its action, important regulatory factors (if applicable) and tissue specificity (if applicable)

DL-1/DL-4

Answer 68

delta-ligand 1 and 4

expressed on TEC’s.

binds Notch receptor on HSC’s to signal commitment to TC lineage

long enough Notch signaling commits to NK cell