CD74

CD74
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD74, DHLAG, HLADG, II, Ia-GAMMA, CD74 molecule, p33
External IDsMGI: 96534 HomoloGene: 3209 GeneCards: CD74
Gene location (Human)
Chr.Chromosome 5 (human)[1]
Band5q33.1Start150,401,637 bp[1]
End150,412,929 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

972

16149

Ensembl

ENSG00000019582

ENSMUSG00000024610

UniProt

P04233

P04441

RefSeq (mRNA)

NM_004355
NM_001025158
NM_001025159
NM_001364083
NM_001364084

NM_001042605
NM_010545

RefSeq (protein)

NP_001020329
NP_001020330
NP_004346
NP_001351012
NP_001351013

NP_001036070
NP_034675

Location (UCSC)Chr 5: 150.4 – 150.41 MbChr 18: 60.8 – 60.81 Mb
PubMed search[3][4]
Wikidata
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.

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.

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

Cancer

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

Axial Spondyloarthritis

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]

Interactions

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

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000019582 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024610 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  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. 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. 1 2 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. ↑ Moonah, Shannon N.; Abhyankar, Mayuresh M.; Haque, Rashidul; Petri, William A.; Appleton, J. A. (September 2014). "The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages". Infection and Immunity. 82 (9): 3523–3530. doi:10.1128/IAI.01812-14. PMC 4187827.
  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

  • Stove V, Verhasselt B (January 2006). "Modelling thymic HIV-1 Nef effects". Current HIV Research. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
  • Riberdy JM, Newcomb JR, Surman MJ, Barbosa JA, Cresswell P (December 1992). "HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides". Nature. 360 (6403): 474–7. doi:10.1038/360474a0. PMID 1448172.
  • Bakke O, Dobberstein B (November 1990). "MHC class II-associated invariant chain contains a sorting signal for endosomal compartments". Cell. 63 (4): 707–16. doi:10.1016/0092-8674(90)90137-4. PMID 2121367.
  • Marks MS, Blum JS, Cresswell P (September 1990). "Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens". The Journal of Cell Biology. 111 (3): 839–55. doi:10.1083/jcb.111.3.839. PMC 2116304. PMID 2391366.
  • Spiro RC, Quaranta V (October 1989). "The invariant chain is a phosphorylated subunit of class II molecules". Journal of Immunology. 143 (8): 2589–94. PMID 2507633.
  • O'Sullivan DM, Noonan D, Quaranta V (August 1987). "Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription/translation". The Journal of Experimental Medicine. 166 (2): 444–60. doi:10.1084/jem.166.2.444. PMC 2189580. PMID 3036998.
  • Genuardi M, Saunders GF (1988). "Localization of the HLA class II-associated invariant chain gene to human chromosome band 5q32". Immunogenetics. 28 (1): 53–6. doi:10.1007/BF00372530. PMID 3132422.
  • O'Sullivan DM, Larhammar D, Wilson MC, Peterson PA, Quaranta V (June 1986). "Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes". Proceedings of the National Academy of Sciences of the United States of America. 83 (12): 4484–8. doi:10.1073/pnas.83.12.4484. PMC 323758. PMID 3459184.
  • Koch N, Hämmerling GJ (October 1985). "Ia-associated invariant chain is fatty acylated before addition of sialic acid". Biochemistry. 24 (22): 6185–90. doi:10.1021/bi00343a023. PMID 3866610.
  • Claesson L, Peterson PA (June 1983). "Association of human gamma chain with class II transplantation antigens during intracellular transport". Biochemistry. 22 (13): 3206–13. doi:10.1021/bi00282a026. PMID 6576808.
  • Strubin M, Mach B, Long EO (April 1984). "The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity". The EMBO Journal. 3 (4): 869–72. PMC 557440. PMID 6586420.
  • Kvist S, Wiman K, Claesson L, Peterson PA, Dobberstein B (May 1982). "Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens". Cell. 29 (1): 61–9. doi:10.1016/0092-8674(82)90090-3. PMID 6955026.
  • Machamer CE, Cresswell P (December 1982). "Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens". Journal of Immunology. 129 (6): 2564–9. PMID 6982931.
  • Ghosh P, Amaya M, Mellins E, Wiley DC (November 1995). "The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3". Nature. 378 (6556): 457–62. doi:10.1038/378457a0. PMID 7477400.
  • Bijlmakers MJ, Benaroch P, Ploegh HL (August 1994). "Mapping functional regions in the lumenal domain of the class II-associated invariant chain". The Journal of Experimental Medicine. 180 (2): 623–9. doi:10.1084/jem.180.2.623. PMC 2191624. PMID 7519244.
  • Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC (July 1993). "Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1". Nature. 364 (6432): 33–9. doi:10.1038/364033a0. PMID 8316295.
  • Naujokas MF, Morin M, Anderson MS, Peterson M, Miller J (July 1993). "The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44". Cell. 74 (2): 257–68. doi:10.1016/0092-8674(93)90417-O. PMID 8343954.
  • Roche PA, Teletski CL, Stang E, Bakke O, Long EO (September 1993). "Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization". Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8581–5. doi:10.1073/pnas.90.18.8581. PMC 47401. PMID 8397411.
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