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CD74 molecule, major histocompatibility complex, class II invariant chain
Protein CD74 PDB 1icf.png
PDB rendering based on 1icf.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM142790 MGI96534 HomoloGene3209 ChEMBL: 4692 GeneCards: CD74 Gene
RNA expression pattern
PBB GE CD74 209619 at tn.png
More reference expression data
Species Human Mouse
Entrez 972 16149
Ensembl ENSG00000019582 ENSMUSG00000024610
UniProt P04233 P04441
RefSeq (mRNA) NM_001025158 NM_001042605
RefSeq (protein) NP_001020329 NP_001036070
Location (UCSC) Chr 5:
150.4 – 150.41 Mb
Chr 18:
60.8 – 60.81 Mb
PubMed search [1] [2]

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.[1][2] The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein.[3] The cell surface form of the invariant chain is known as CD74.


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[edit]

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

Possible interactions[edit]

In limited cases, CD74 might interact with Macrophage migration inhibitory factor.[4]

See also[edit]


  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 

Further reading[edit]

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