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NameHLA class II histocompatibility antigen, DR alpha chain
Synonyms
  • HLA-DRA1
  • MHC class II antigen DRA
Gene NameHLA-DRA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009228|HLA class II histocompatibility antigen, DR alpha chain
MAISGVPVLGFFIIAVLMSAQESWAIKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVD
MAKKETVWRLEEFGRFASFEAQGALANIAVDKANLEIMTKRSNYTPITNVPPEVTVLTNS
PVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLP
STEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIK
GVRKSNAAERRGPL
Number of residues254
Molecular Weight28606.685
Theoretical pINot Available
GO Classification
Functions
  • MHC class II protein complex binding
  • MHC class II receptor activity
  • peptide antigen binding
Processes
  • antigen processing and presentation of exogenous peptide antigen via MHC class II
  • cognition
  • cytokine-mediated signaling pathway
  • antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
  • peptide antigen assembly with MHC class II protein complex
  • polysaccharide assembly with MHC class II protein complex
  • T cell costimulation
  • T cell receptor signaling pathway
  • viral process
  • immune response
  • interferon-gamma-mediated signaling pathway
Components
  • clathrin-coated endocytic vesicle membrane
  • integral component of plasma membrane
  • integral component of lumenal side of endoplasmic reticulum membrane
  • Golgi membrane
  • MHC class II protein complex
  • trans-Golgi network membrane
  • endocytic vesicle membrane
  • lysosomal membrane
  • plasma membrane
  • transport vesicle membrane
  • lysosome
  • ER to Golgi transport vesicle membrane
  • cell surface
  • late endosome membrane
  • extracellular exosome
General FunctionPeptide antigen binding
Specific FunctionBinds 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.
Pfam Domain Function
Transmembrane Regions217-239
GenBank Protein IDNot Available
UniProtKB IDP01903
UniProtKB Entry NameDRA_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0013684|HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)
ATGGCCATAAGTGGAGTCCCTGTGCTAGGATTTTTCATCATAGCTGTGCTGATGAGCGCT
CAGGAATCATGGGCTATCAAAGAAGAACATGTGATCATCCAGGCCGAGTTCTATCTGAAT
CCTGACCAATCAGGCGAGTTTATGTTTGACTTTGATGGTGATGAGATTTTCCATGTGGAT
ATGGCAAAGAAGGAGACGGTCTGGCGGCTTGAAGAATTTGGACGATTTGCCAGCTTTGAG
GCTCAAGGTGCATTGGCCAACATAGCTGTGGACAAAGCCAACCTGGAAATCATGACAAAG
CGCTCCAACTATACTCCGATCACCAATGTACCTCCAGAGGTAACTGTGCTCACAAACAGC
CCTGTGGAACTGAGAGAGCCCAACGTCCTCATCTGTTTCATAGACAAGTTCACCCCACCA
GTGGTCAATGTCACGTGGCTTCGAAATGGAAAACCTGTCACCACAGGAGTGTCAGAGACA
GTCTTCCTGCCCAGGGAAGACCACCTTTTCCGCAAGTTCCACTATCTCCCCTTCCTGCCC
TCAACTGAGGACGTTTACGACTGCAGGGTGGAGCACTGGGGCTTGGATGAGCCTCTTCTC
AAGCACTGGGAGTTTGATGCTCCAAGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGT
GCCCTGGGCCTGACTGTGGGTCTGGTGGGCATCATTATTGGGACCATCTTCATCATCAAG
GGATTGCGCAAAAGCAATGCAGCAGAACGCAGGGGGCCTCTGTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:4947
Chromosome Location6
LocusNot Available
References
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