CPLM-001927

Genbank Nucleotide ID

HLA class II histocompatibility antigen, DR alpha chain

Protein Synonyms/Alias

MHC class II antigen DRA

Homo sapiens (Human)

Position	Peptide	Type	References
92	LANIAVDKANLEIMT	ubiquitination	[1]
100	ANLEIMTKRSNYTPI	ubiquitination	[1]
151	VTWLRNGKPVTTGVS	ubiquitination	[1]
172	REDHLFRKFHYLPFL	ubiquitination	[1]
244	FIIKGVRKSNAAERR	ubiquitination	[2]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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 miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

DOMAIN 112 204 Ig-like C1-type.
REGION 26 109 Alpha-1.
REGION 110 203 Alpha-2.
REGION 204 216 Connecting peptide.
CARBOHYD 103 103 N-linked (GlcNAc...).
CARBOHYD 143 143 N-linked (GlcNAc...).
DISULFID 132 188
CROSSLNK 244 244 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Cell membrane; Complete proteome; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Immunity; Isopeptide bond; Lysosome; Membrane; MHC II; Polymorphism; Reference proteome; Signal; Transmembrane; Transmembrane helix; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
GO:0000139; C:Golgi membrane; TAS:Reactome.
GO:0071556; C:integral to lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
GO:0031902; C:late endosome membrane; IDA:UniProtKB.
GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
GO:0042613; C:MHC class II protein complex; IEA:UniProtKB-KW.
GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
GO:0032395; F:MHC class II receptor activity; NAS:UniProtKB.
GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
GO:0031295; P:T cell costimulation; TAS:Reactome.
GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.

IPR007110; Ig-like_dom.
IPR013783; Ig-like_fold.
IPR003006; Ig/MHC_CS.
IPR003597; Ig_C1-set.
IPR011162; MHC_I/II-like_Ag-recog.
IPR014745; MHC_II_a/b_N.
IPR001003; MHC_II_a_N.

PF07654; C1-set
PF00993; MHC_II_alpha

SM00407; IGc1
SM00920; MHC_II_alpha

PS50835; IG_LIKE
PS00290; IG_MHC