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Protein CD74 PDB 1icf.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesCD74, DHLAG, HLADG, II, Ia-GAMMA, CD74 molecule, p33
External IDsOMIM: 142790 MGI: 96534 HomoloGene: 3209 GeneCards: CD74
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for CD74
Genomic location for CD74
Band5q33.1Start150,400,041 bp[1]
End150,412,929 bp[1]
RNA expression pattern
PBB GE CD74 209619 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 5: 150.4 – 150.41 MbChr 18: 60.8 – 60.81 Mb
PubMed search[3][4]
View/Edit HumanView/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.[5][6] The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein.[7] 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.

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 antigen proteins (from the exogenous pathway). Binding to Ii ensures that no antigen peptides from the endogenous pathway meant for MHC class I molecules accidentally bind to the groove of MHC class II molecules.[8] The Ii is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP remaining bound to the groove of MHC class II molecules. The rest of the Ii is degraded.[8] CLIP blocks peptide binding until HLA-DM interacts with MHC II, releasing CLIP and allowing other peptides to bind. In some cases, CLIP dissociates without any further molecular interactions, but in other cases the binding to the MHC is more stable.[9]

The stable MHC class-II with antigen complex is then presented on the cell surface. Without CLIP, MHC class II aggregates, disassemble, and/or denature in the endosomes, and proper antigen presentation is impaired[10]

Clinical significance[edit]


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

Axial Spondyloarthritis[edit]

Autoantibodies against CD74 have been identified as a promising biomarkers in the early diagnosis of the autoimmune disease called axial spondyloarthritis (non-radiographic axial Spondyloarthritis and radiographic axial Spondyloarthritis / Ankylosing spondylitis). [11]


CD74 receptor interacts with the cytokine Macrophage migration inhibitory factor to mediate its proinflammatory functions[12][13][14][15][16][17]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000019582 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024610 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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". Proceedings of the National Academy of Sciences of the United States of America. 80 (24): 7395–9. Bibcode:1983PNAS...80.7395C. doi:10.1073/pnas.80.24.7395. PMC 389957. PMID 6324166.
  6. ^ 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 Research. 13 (24): 8827–41. doi:10.1093/nar/13.24.8827. PMC 318954. PMID 3001652.
  7. ^ Cresswell P (1994). "Assembly, transport, and function of MHC class II molecules". Annual Review of Immunology. 12: 259–93. doi:10.1146/annurev.iy.12.040194.001355. PMID 8011283.
  8. ^ a b Owen JA, Punt J, Stranford SA, Jones PP, Kuby J (2013). Kuby immunology (7th ed.). New York: W.H. Freeman. ISBN 978-1-4641-1991-0. OCLC 820117219.
  9. ^ Schulze MS, Wucherpfennig KW (February 2012). "The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway". Current Opinion in Immunology. 24 (1): 105–11. doi:10.1016/j.coi.2011.11.004. PMC 3288754. PMID 22138314.
  10. ^ Vogt AB, Kropshofer H (April 1999). "HLA-DM - an endosomal and lysosomal chaperone for the immune system". Trends in Biochemical Sciences. 24 (4): 150–4. doi:10.1016/s0968-0004(99)01364-x. PMID 10322421.
  11. ^ Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, Witte T (June 2014). "Autoantibodies against CD74 in spondyloarthritis". Annals of the Rheumatic Diseases. 73 (6): 1211–4. doi:10.1136/annrheumdis-2012-202208. PMID 23687263.
  12. ^ Ghosh, S; Padalia, J; Ngobeni, R; Abendroth, J; Farr, L; Shirley, DA; Edwards, T; Moonah, S (2 November 2019). "Targeting parasite-produced MIF as an anti-virulence strategy with antibiotic-antibody combination to reduce tissue damage". The Journal of Infectious Diseases. doi:10.1093/infdis/jiz579. PMID 31677380.
  13. ^ 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 = Journal of Southern Medical University (in Chinese). 29 (12): 2383–6, 2390. PMID 20034881.
  14. ^ 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.
  15. ^ 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 Science. 18 (12): 2578–91. doi:10.1002/pro.263. PMC 2798171. PMID 19827093.
  16. ^ 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". The Journal of Biological Chemistry. 284 (47): 32483–92. doi:10.1074/jbc.M109.014589. PMC 2781663. PMID 19759012.
  17. ^ Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E, Bernhagen J (July 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]

External links[edit]