2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain

2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain » Clone P2-beta-3;MHC class II antigen DRB1*3;
Hydrophobic Thickness 33.2 ± 1.4 Å
Tilt Angle 1 ± 0°
ΔGtransfer -40.9 kcal/mol
ΔGfold -15.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 228-250 (222-253)
Pathways

Allograft rejection (KEGG)

Antigen processing and presentation (KEGG)

Asthma (KEGG)

Autoimmune thyroid disease (KEGG)

Cell adhesion molecules (KEGG)

Epstein-Barr virus infection (KEGG)

Graft-versus-host disease (KEGG)

Hematopoietic cell lineage (KEGG)

Herpes simplex infection (KEGG)

HTLV-I infection (KEGG)

Immune System (Reactome)

Influenza A (KEGG)

Intestinal immune network for IgA production (KEGG)

Leishmaniasis (KEGG)

Phagosome (KEGG)

Rheumatoid arthritis (KEGG)

Staphylococcus aureus infection (KEGG)

Systemic lupus erythematosus (KEGG)

Toxoplasmosis (KEGG)

Tuberculosis (KEGG)

Type I diabetes mellitus (KEGG)

Viral myocarditis (KEGG)

PDB 1a6a (B=34-220)
OPM none
Complexes

2B13:HG2A:DRA_HUMAN

Interactions

2B1F, Complex: 2B13:2B1F

AT1B1, Complex: AT1B1:2B13.2B1F.2B1G, PubMed

DMA, Complex: 2B13.2B1F.2B1G:DMA, PubMed

DRA, Complex: 2B13.2B1F.2B1G:DRA:MBP, PubMed

HG2A, Complex: 2B13:HG2A:DRA, PDBID: 1A6A

Domains

AA: 42-116, PDBID: 1A6A, Subunit B, Seq Identity:100%, Class II histocompatibility antigen, beta domain

AA: 126-209, PDBID: 1A6A, Subunit B, Seq Identity:100%, Immunoglobulin C1-set domain

UniProt annotation for 2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain
FUNCTION: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.

SUBUNIT: Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.

UniProt features for 2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain
SIGNAL 1 29
CHAIN 30 266 HLA class II histocompatibility antigen, DRB1-3 chain.
DOMAIN 126 214 Ig-like C1-type.
REGION 30 123 Beta-1.
REGION 124 217 Beta-2.
REGION 218 227 Connecting peptide.
DISULFID 44 108
DISULFID 146 202
CROSSLNK 254 254 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) (By similarity).
Amino Acid Sequence for 2B13_HUMAN » HLA class II histocompatibility antigen, DRB1-3 chain
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TSECHFFNGT ERVRYLDRYF HNQEENVRFD SDVGEFRAVT ELGRPDAEYW NSQKDLLEQK RGRVDNYCRH NYGVVESFTV QRRVHPKVTV YPSKTQPLQH HNLLVCSVSG FYPGSIEVRW FRNGQEEKTG VVSTGLIHNG DWTFQTLVML ETVPRSGEVY TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF RNQKGHSGLQ PRGFLS