HLA-DRB4
entrez
3126
canonical
uniprot
P13762
canonical
ensembl
ENSG00000227357
resolver
ensembl
ENSG00000231021
resolver
ensp
ENSP00000410857
resolver
ensp
ENSP00000412031
resolver
enst
ENST00000411565
resolver
enst
ENST00000457451
resolver
genesymbol
HLA-DRB4
resolver
hgnc
HGNC:4952
resolver
uniprot
A0A2K9UW88
resolver
uniprot
A0A2K9UW93
resolver
uniprot
B0S863
resolver
uniprot
O78042
resolver
uniprot
P79664
resolver
uniprot
Q29889
resolver
uniprot
Q30163
resolver
uniprot
Q6TLK6
resolver
uniprot
Q860N4
resolver
uniprot
Q861F3
resolver
uniprot
Q8WLT9
resolver
uniprot
Q9BS54
resolver
uniprot
X5D2U9
resolver
uniprot_entry
DRB4_HUMAN
resolver
uniprot_entry
X5D2U9_HUMAN
resolver
uniprot_sec
A0A2K9UW88
resolver
uniprot_sec
A0A2K9UW93
resolver
uniprot_sec
B0S863
resolver
uniprot_sec
O78042
resolver
uniprot_sec
P79664
resolver
uniprot_sec
Q29889
resolver
uniprot_sec
Q30163
resolver
uniprot_sec
Q6TLK6
resolver
uniprot_sec
Q860N4
resolver
uniprot_sec
Q861F3
resolver
uniprot_sec
Q8WLT9
resolver
uniprot_sec
Q9BS54
resolver
amino_acid_sequence
MVCLKLPGGSCMAALTVTLTVLSSPLALAGDTQPRFLEQAKCECHFLNGTERVWNLIRYIYNQEEYARYNSDLGEYQAVTELGRPDAEYWNSQKDLLERRRAEVDTYCRYNYGVVESFTVQRRVQPKVTVYPSKTQPLQHHNLLVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSMMSPLTVQWSARSESAQSKMLSGVGGFVLGLLFLGTGLFIYFRNQKGHSGLQPTGLLS
uniprot
proteins
function
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.
uniprot
proteins
mass_dalton
29941
uniprot
proteins
mutagenesis
MUTAGEN 254; /note="K->R: Almost no change in down-regulation of MHC class II. No ubiquitination and complete loss of down-regulation of MHC class II; when associated with 'R-244' of HLA-DRA."; /evidence="ECO:0000269|PubMed:19117940"; MUTAGEN 264; /note="L->A: Almost no change in down-regulation of MHC class II; when associated with A-265."; /evidence="ECO:0000269|PubMed:19117940"; MUTAGEN 265; /note="L->A: Almost no change in down-regulation of MHC class II; when associated with A-264."; /evidence="ECO:0000269|PubMed:19117940
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II. When associated with ubiquitination of the alpha subunit of HLA-DR: HLA-DRA 'Lys-244', the down-regulation of MHC class II may be highly effective. {ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:19117940}.
uniprot
proteins
protein_family
MHC class II family
uniprot
proteins
pubmed
11684289
uniprot
proteins
pubmed
11972878
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17241953
uniprot
proteins
pubmed
18046453
uniprot
proteins
pubmed
18305173
uniprot
proteins
pubmed
19092054
uniprot
proteins
pubmed
19117940
uniprot
proteins
pubmed
19533806
uniprot
proteins
pubmed
3036826
uniprot
proteins
pubmed
3110774
uniprot
proteins
pubmed
3467350
uniprot
proteins
pubmed
8598037
uniprot
proteins
pubmed
9234493
uniprot
proteins
sequence_length
266
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Late endosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.
uniprot
proteins
transmembrane_region
TRANSMEM 228..250; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins