Invariant chain

1A6A, 1ICF, 1IIE, 1L3H, 1MUJ, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 4AEN, 4X5W97216149ENSG00000019582ENSMUSG00000024610P04233P04441NM_004355NM_001025158NM_001025159NM_001364083NM_001364084NM_001042605NM_010545NP_001020329NP_001020330NP_004346NP_001351012NP_001351013NP_001036070NP_034675HLA 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 CD74.1icf: CRYSTAL STRUCTURE OF MHC CLASS II ASSOCIATED P41 II FRAGMENT IN COMPLEX WITH CATHEPSIN L1iie: HLA-DR ANTIGENS ASSOCIATED INVARIANT CHAIN1l3h: NMR structure of P41icf, a potent inhibitor of human cathepsin L 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. 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. 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 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 Found on a number of cancer cell types. Possible cancer therapy target. See Milatuzumab#CD74 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). CD74 receptor interacts with the cytokine Macrophage migration inhibitory factor to mediate its proinflammatory functions.