CD74

CD74
Available structures PDB 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, p33, CLIP
External IDs	OMIM: 142790; MGI: 96534; HomoloGene: 3209; GeneCards: CD74; OMA:CD74 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q33.1 Start 150,401,637 bp End 150,412,969 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18 E1|18 34.41 cM Start 60,936,920 bp End 60,945,724 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte appendix granulocyte spleen lymph node right lung gallbladder upper lobe of left lung lower lobe of lung mucosa of ileum Top expressed in spleen jejunum thymus ileum zone of skin colon lip uterus adrenal gland white adipose tissue More reference expression data BioGPS More reference expression data
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 folding chaperone activity MHC class II protein complex binding amyloid-beta binding protein binding MHC class II protein binding cytokine binding CD4 receptor 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 anatomical structure 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 cofactor-dependent protein refolding T cell selection 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 positive regulation of chemokine (C-X-C motif) ligand 2 production macrophage migration inhibitory factor signaling pathway prostaglandin biosynthetic process cell population 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 positive regulation of protein phosphorylation positive regulation of kinase activity positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of MAPK cascade positive regulation of monocyte differentiation positive regulation of transcription, DNA-templated positive regulation of viral entry into host cell protein heterotetramerization protein trimerization protein-containing complex assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 18: 60.94 – 60.95 Mb PubMed search
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. The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein. 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.

See also

• Cluster of differentiation
• Milatuzumab the first Mab to target CD74

Further reading

• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Riberdy JM; Newcomb JR; Surman MJ; et al. (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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
• Bakke O, Dobberstein B (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 (1990). "Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens". J. Cell Biol. 111 (3): 839–55. doi:10.1083/jcb.111.3.839. PMC 2116304. PMID 2391366.
• Spiro RC, Quaranta V (1989). "The invariant chain is a phosphorylated subunit of class II molecules". J. Immunol. 143 (8): 2589–94. PMID 2507633.
• O'Sullivan DM, Noonan D, Quaranta V (1987). "Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription/translation". J. Exp. Med. 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; et al. (1986). "Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes". Proc. Natl. Acad. Sci. U.S.A. 83 (12): 4484–8. doi:10.1073/pnas.83.12.4484. PMC 323758. PMID 3459184. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
• Koch N, Hämmerling GJ (1986). "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 (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 (1984). "The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity". EMBO J. 3 (4): 869–72. PMC 557440. PMID 6586420.
• Kvist S; Wiman K; Claesson L; et al. (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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
• Machamer CE, Cresswell P (1983). "Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens". J. Immunol. 129 (6): 2564–9. PMID 6982931.
• Ghosh P, Amaya M, Mellins E, Wiley DC (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 (1994). "Mapping functional regions in the lumenal domain of the class II- associated invariant chain". J. Exp. Med. 180 (2): 623–9. doi:10.1084/jem.180.2.623. PMC 2191624. PMID 7519244.
• Brown JH; Jardetzky TS; Gorga JC; et al. (1993). "Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1". Nature. 364 (6432): 33–9. doi:10.1038/364033a0. PMID 8316295. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
• Naujokas MF; Morin M; Anderson MS; et al. (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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
• Roche PA; Teletski CL; Stang E; et al. (1993). "Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization". Proc. Natl. Acad. Sci. U.S.A. 90 (18): 8581–5. doi:10.1073/pnas.90.18.8581. PMC 47401. PMID 8397411. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

External links

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