CD74

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1A6A, 1ICF, 1IIE, 1L3H, 1MUJ, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 4AEN, 4X5W

Identifiers

Aliases

CD74, DHLAG, HLADG, II, Ia-GAMMA, CD74 molecule

External IDs

MGI: 96534 HomoloGene: 3209 GeneCards: CD74

Gene ontology
Molecular function	• nitric-oxide synthase binding • identical protein binding • MHC class II protein binding, via antigen binding groove • cytokine receptor activity • macrophage migration inhibitory factor binding • protein binding involved in protein folding • MHC class II protein complex binding • beta-amyloid binding • protein binding • MHC class II protein binding • cytokine binding
Cellular component	• lysosomal lumen • extracellular exosome • MHC class II protein complex • lysosomal membrane • late endosome • endocytic vesicle membrane • transport vesicle membrane • integral component of membrane • ER to Golgi transport vesicle membrane • multivesicular body • Golgi apparatus • Golgi membrane • trans-Golgi network membrane • macrophage migration inhibitory factor receptor complex • membrane • cell surface • intracellular • integral component of lumenal side of endoplasmic reticulum membrane • endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane • lysosome • vacuole • endosome • clathrin-coated endocytic vesicle membrane • NOS2-CD74 complex • external side of plasma membrane
Biological process	• immune response • positive regulation of T cell differentiation • negative regulation of apoptotic process • signal transduction • positive thymic T cell selection • chaperone mediated protein folding requiring cofactor • T cell selection • activation of MAPK activity • positive regulation of type 2 immune response • positive regulation of dendritic cell antigen processing and presentation • antigen processing and presentation of exogenous peptide antigen via MHC class II • adaptive immune response • antigen processing and presentation • positive regulation of peptidyl-tyrosine phosphorylation • negative regulation of mature B cell apoptotic process • regulation of macrophage activation • negative regulation of DNA damage response, signal transduction by p53 class mediator • immunoglobulin mediated immune response • leukocyte migration • positive regulation of neutrophil chemotaxis • protein complex assembly • positive regulation of chemokine (C-X-C motif) ligand 2 production • macrophage migration inhibitory factor signaling pathway • prostaglandin biosynthetic process • cell proliferation • antigen processing and presentation of endogenous antigen • immune system process • defense response • negative regulation of peptide secretion • negative regulation of T cell differentiation • positive regulation of macrophage cytokine production • positive regulation of B cell proliferation • negative thymic T cell selection • positive regulation of fibroblast proliferation • intracellular protein transport • positive regulation of ERK1 and ERK2 cascade • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • positive regulation of cytokine-mediated signaling pathway
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


972


16149

Ensembl


ENSG00000019582


ENSMUSG00000024610

UniProt


P04233


P04441

RefSeq (mRNA)


NM_004355 NM_001025158 NM_001025159


NM_001042605 NM_010545

RefSeq (protein)


NP_001020329.1 NP_001020330.1 NP_004346.1


NP_001036070.1

Location (UCSC)

Chr 5: 150.4 – 150.41 Mb

Chr 18: 60.8 – 60.81 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 (Cluster of Differentiation 74), is a protein that in humans is encoded by the CD74 gene.^[3]^[4] The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein.^[5] The cell surface form of the invariant chain is known as CD74.

Function

The nascent MHC class II protein in the rough ER binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation. Binding to Ii might also prevent binding of peptides from the endogenous pathway to the groove of MHC class II. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM interacts with MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.

Clinical significance

Found on a number of cancer cell types. Possible cancer therapy target. See Milatuzumab#CD74

Possible interactions

In limited cases, CD74 might interact with Macrophage migration inhibitory factor.^[6]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Claesson L, Larhammar D, Rask L, Peterson PA (December 1983). "cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure". Proc. Natl. Acad. Sci. U.S.A. 80 (24): 7395–9. doi:10.1073/pnas.80.24.7395. PMC 389957. PMID 6324166.
↑ Kudo J, Chao LY, Narni F, Saunders GF (December 1985). "Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens". Nucleic Acids Res. 13 (24): 8827–41. doi:10.1093/nar/13.24.8827. PMC 318954. PMID 3001652.
↑ Cresswell P (1994). "Assembly, transport, and function of MHC class II molecules". Annu. Rev. Immunol. 12: 259–93. doi:10.1146/annurev.iy.12.040194.001355. PMID 8011283.
↑ Shan ZX, Lin QX, Deng CY, Tan HH, Kuang SJ, Xiao DZ, Zhu JN, Fu YH, Yu XY (December 2009). "[Identification of the interactions between the truncated fragments of macrophage migration inhibitory factor and CD74 using a yeast two-hybrid system]". Nan Fang Yi Ke Da Xue Xue Bao (in Chinese). 29 (12): 2383–6, 2390. PMID 20034881. Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J (February 2010). "Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats". Pain. 148 (2): 275–83. doi:10.1016/j.pain.2009.11.011. PMID 20005040. Dobson SE, Augustijn KD, Brannigan JA, Schnick C, Janse CJ, Dodson EJ, Waters AP, Wilkinson AJ (December 2009). "The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei". Protein Sci. 18 (12): 2578–91. doi:10.1002/pro.263. PMC 2798171. PMID 19827093. Piette C, Deprez M, Roger T, Noël A, Foidart JM, Munaut C (November 2009). "The Dexamethasone-induced Inhibition of Proliferation, Migration, and Invasion in Glioma Cell Lines Is Antagonized by Macrophage Migration Inhibitory Factor (MIF) and Can Be Enhanced by Specific MIF Inhibitors". J. Biol. Chem. 284 (47): 32483–92. doi:10.1074/jbc.M109.014589. PMC 2781663. PMID 19759012. Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E, Bernhagen J (2009). "Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer". BMC Cancer. 9: 230. doi:10.1186/1471-2407-9-230. PMC 2716369. PMID 19602265.

External links

CD74 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
Overview at Davidson College (student generated)
School of Crystallography The Invariant Chain

PDB gallery

1icf: CRYSTAL STRUCTURE OF MHC CLASS II ASSOCIATED P41 II FRAGMENT IN COMPLEX WITH CATHEPSIN L

1iie: HLA-DR ANTIGENS ASSOCIATED INVARIANT CHAIN

1l3h: NMR structure of P41icf, a potent inhibitor of human cathepsin L

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50

51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100

101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150

151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200

201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249

251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299

301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

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