HLA class II histocompatibility antigen gamma chain

Function

Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.

Classification

Family (Pfam)

PF09307 MHC2-interact, PF08831 MHCassoc_trimer, PF00086 Thyroglobulin_1

InterPro

CD74_antigen, MHC-II_Gamma/Thyroglobulin, MHC_II-assoc_invar/CLIP_MHC-bd, MHC_II-assoc_invar_chain, MHC_II-assoc_invariant_trimer, MHCII_invariant_trimer_sf, Thyroglobulin_1, Thyroglobulin_1_sf

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 24

• 1A6A X-ray 2.75A
• 1ICF X-ray 2.00A
• 1IIE NMR
• 1L3H NMR
• 1MUJ X-ray 2.15A
• 3PDO X-ray 1.95A
• 3PGC X-ray 2.66A
• 3PGD X-ray 2.72A
• 3QXA X-ray 2.71A
• 3QXD X-ray 2.30A
• 4AEN X-ray 2.20A
• 4AH2 X-ray 2.36A
• … and 12 more

A predicted model is available from AlphaFold.

Gene Ontology · 73

• GO:0009986 cell surface
• GO:0030669 clathrin-coated endocytic vesicle membrane
• GO:0005737 cytoplasm
• GO:0030666 endocytic vesicle membrane
• GO:0012507 ER to Golgi transport vesicle membrane
• GO:0009897 external side of plasma membrane
• GO:0070062 extracellular exosome
• GO:0005794 Golgi apparatus
• GO:0000139 Golgi membrane
• GO:0005770 late endosome
• GO:0098553 lumenal side of endoplasmic reticulum membrane
• GO:0043202 lysosomal lumen
• GO:0005765 lysosomal membrane
• GO:0005764 lysosome
• GO:0035692 macrophage migration inhibitory factor receptor complex
• GO:0016020 membrane
• GO:0042613 MHC class II protein complex
• GO:0005771 multivesicular body
• GO:0035693 NOS2-CD74 complex
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:0032588 trans-Golgi network membrane
• GO:0030658 transport vesicle membrane
• GO:0005773 vacuole
• GO:0001540 amyloid-beta binding
• GO:0042609 CD4 receptor binding
• GO:0019955 cytokine binding
• GO:0004896 cytokine receptor activity
• GO:0042802 identical protein binding
• GO:0035718 macrophage migration inhibitory factor binding
• GO:0042289 MHC class II protein binding
• GO:0042658 MHC class II protein binding, via antigen binding groove
• GO:0023026 MHC class II protein complex binding
• GO:0050998 nitric-oxide synthase binding
• GO:0044183 protein folding chaperone
• GO:0019882 antigen processing and presentation
• GO:0019883 antigen processing and presentation of endogenous antigen
• GO:0046597 host-mediated suppression of symbiont invasion
• GO:0016064 immunoglobulin mediated immune response
• GO:0006886 intracellular protein transport
• GO:0035691 macrophage migration inhibitory factor signaling pathway
• GO:0043066 negative regulation of apoptotic process
• GO:0030336 negative regulation of cell migration
• GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator
• GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• GO:0002906 negative regulation of mature B cell apoptotic process
• GO:0002792 negative regulation of peptide secretion
• GO:0030890 positive regulation of B cell proliferation
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production
• GO:0032722 positive regulation of chemokine production
• GO:0001961 positive regulation of cytokine-mediated signaling pathway
• GO:0002606 positive regulation of dendritic cell antigen processing and presentation
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0048146 positive regulation of fibroblast proliferation
• GO:0010628 positive regulation of gene expression
• GO:0032755 positive regulation of interleukin-6 production
• GO:0032757 positive regulation of interleukin-8 production
• GO:0060907 positive regulation of macrophage cytokine production
• GO:2000448 positive regulation of macrophage migration inhibitory factor signaling pathway
• GO:0045657 positive regulation of monocyte differentiation
• GO:0090023 positive regulation of neutrophil chemotaxis
• GO:0031394 positive regulation of prostaglandin biosynthetic process
• GO:0002830 positive regulation of type 2 immune response
• GO:0001516 prostaglandin biosynthetic process
• GO:0050821 protein stabilization
• GO:0070206 protein trimerization
• GO:0065003 protein-containing complex assembly
• GO:0043030 regulation of macrophage activation
• GO:0034341 response to type II interferon
• GO:0002286 T cell activation involved in immune response
• GO:0045058 T cell selection

Drugs targeting this protein · 1

• REPOTRECTINIB inhibitor

Related proteins · sequence + function similarity

• H-2 class II histocompatibility antigen gamma chain 0.97
• H-2 class II histocompatibility antigen gamma chain 0.96
• Fibroblast growth factor-binding protein 1 0.51
• Clusterin-like protein 1 0.51
• Clusterin-like protein 1 0.51
• CD27 antigen 0.50
• CD27 antigen 0.50
• Collagen and calcium-binding EGF domain-containing protein 1 0.50
• Clusterin-like protein 1 0.50
• SPARC-related modular calcium-binding protein 1 0.50
• Chordin-like protein 2 0.50
• Beta-galactoside alpha-2,6-sialyltransferase 2 0.49

Co-cited proteins · studied together in the literature

• Sodium-dependent phosphate transport protein 2B 1 shared papers
• Macrophage migration inhibitory factor 1 shared papers
• Proto-oncogene tyrosine-protein kinase ROS 1 shared papers
• MHC class II transactivator 1 shared papers
• H-2 class II histocompatibility antigen gamma chain 1 shared papers
• Golgi-associated PDZ and coiled-coil motif-containing protein 1 shared papers
• HLA class II histocompatibility antigen, DR alpha chain 1 shared papers
• Collagen alpha-1(XV) chain 4 shared papers
• MHC class II transactivator 1 shared papers
• Collagen and calcium-binding EGF domain-containing protein 1 4 shared papers
• Laminin subunit alpha-4 4 shared papers
• HLA class II histocompatibility antigen, DRB1 beta chain 1 shared papers

Literature · 25 cited papers

• Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics. Mol. Cell. Proteomics · 2023
• Mass spectrometric analysis of chondroitin sulfate-linked peptides. J. Proteins Proteom. · 2022
• MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses. Science · 2020
• An affinity chromatography and glycoproteomics workflow to profile the chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in the placenta and in cancer. Glycobiology · 2020
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Identification of chondroitin sulfate linkage region glycopeptides reveals prohormones as a novel class of proteoglycans. Mol. Cell. Proteomics · 2015
• LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins. J. Proteome Res. · 2013
• Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. Mol. Cell. Proteomics · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome Res. · 2009
• MHC class II transport at a glance. J. Cell Sci. · 2009
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 13 more in the literature graph