cd74 cd74 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 which plays a critical role in antigen presentation. it is involved in the formation and transport of mhc class ii peptide complexes for the generation of cd4+ t cell responses. the cell surface form of the invariant chain is known as cd74. cd74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (mif). cd74available structurespdbortholog search: pdbe rcsb list of pdb id codes1a6a, 1icf, 1iie, 1l3h, 1muj, 3pdo, 3pgc, 3pgd, 3qxa, 3qxd, 4aen, 4x5widentifiersaliasescd74, dhlag, hladg, ii, ia-gamma, cd74 molecule, p33, clipexternal idsomim: 142790 mgi: 96534 homologene: 3209 genecards: cd74 gene location (human)chr.chromosome 5 (human)band5q33.1start150,401,637 bpend150,412,969 bpgene location (mouse)chr.chromosome 18 (mouse)band18 e1|18 34.41 cmstart60,936,920 bpend60,945,724 bprna expression patternbgeehumanmouse (ortholog)top expressed inmonocyteappendixspleenlymph noderight lunggallbladderupper lobe of left lunglower lobe of lungjejunal mucosaright coronary arterytop expressed inspleenjejunumthymusileumzone of skincolonliputerusadrenal glandwhite adipose tissuemore reference expression databiogpsmore reference expression datagene ontologymolecular 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 / quickgoorthologsspecieshumanmouseentrez97216149ensemblensg00000019582ensmusg00000024610uniprotp04233p04441refseq (mrna)nm_004355nm_001025158nm_001025159nm_001364083nm_001364084nm_001042605nm_010545refseq (protein)np_001020329np_001020330np_004346np_001351012np_001351013np_001036070np_034675location (ucsc)chr 5: 150.4 – 150.41 mbchr 18: 60.94 – 60.95 mbpubmed searchwikidataview/edit humanview/edit mouse function the nascent mhc class ii protein in the rough endoplasmic reticulum (rer) binds a segment of the invariant chain (ii; a trimer) in order to shape the peptide-binding groove and prevent the formation of a closed conformation. the invariant chain also facilitates the export of mhc class ii from the rer 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. 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. 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. the stable mhc class ii + 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. clinical significance vaccine adjuvant the ii molecule—fused with a viral vector to a conserved region of the hepatitis c virus (hcv) genome—has been tested as an adjuvant for a hcv vaccine in a cohort of 17 healthy human volunteers. this experimental vaccine was well-tolerated, and those who received the adjuvanted vaccine had stronger anti-hcv immune responses (enhanced magnitude, breadth and proliferative capacity of anti-hcv-specific t-cells) compared with volunteers who received the vaccine that lacked the ii adjuvant. the ii molecule might also prove to be useful as an adjuvant for a future vaccine for the sars-cov-2 virus, if this enhancing effect can be demonstrated to apply to the appropriate antigen(s). cancer found on a number of cancer cell types. possible cancer therapy target. see milatuzumab. axial spondyloarthritis autoantibodies against cd74 have been identified as promising biomarkers in the early diagnosis of the autoimmune disease called axial spondyloarthritis (non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis / ankylosing spondylitis). interactions cd74 receptor interacts with the cytokine macrophage migration inhibitory factor (mif) to mediate some of its functions. recovery functions role of cd74 receptor in tissue injury and wound repair cd74 receptor is expressed on the surface of different cell types. interaction between mif cytokine and its cell membrane receptor cd74 activates pro-survival and proliferative pathways that protect against injury and promote healing in different parts of the body. history the invariant chain was first described by patricia p. jones, donal b. murphy, derek hewgill, and hugh mcdevitt at stanford. the nomenclature "ii" comes from an ix-based naming system (i for immune) that predates the naming of the major histocompatibility complex.