HLA class II histocompatibility antigen, DR beta 4 chain

Details

Name

HLA class II histocompatibility antigen, DR beta 4 chain

Synonyms

• MHC class II antigen DRB4

Gene Name

HLA-DRB4

Organism

Humans

Amino acid sequence

>lcl|BSEQ0052162|HLA class II histocompatibility antigen, DR beta 4 chain
MVCLKLPGGSCMAALTVTLTVLSSPLALAGDTQPRFLEQAKCECHFLNGTERVWNLIRYI
YNQEEYARYNSDLGEYQAVTELGRPDAEYWNSQKDLLERRRAEVDTYCRYNYGVVESFTV
QRRVQPKVTVYPSKTQPLQHHNLLVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNG
DWTFQTLVMLETVPRSGEVYTCQVEHPSMMSPLTVQWSARSESAQSKMLSGVGGFVLGLL
FLGTGLFIYFRNQKGHSGLQPTGLLS

Number of residues

266

Molecular Weight

29940.945

Theoretical pI

Not Available

GO Classification

Processes

adaptive immune response / antigen processing and presentation of exogenous peptide antigen via MHC class II / interferon-gamma-mediated signaling pathway / T cell receptor signaling pathway

Components

clathrin-coated endocytic vesicle membrane / endocytic vesicle membrane / ER to Golgi transport vesicle membrane / Golgi membrane / integral component of lumenal side of endoplasmic reticulum membrane / late endosome membrane / lysosomal membrane / MHC class II protein complex / plasma membrane / trans-Golgi network membrane / transport vesicle membrane

General 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.

Specific Function

Not Available

Pfam Domain Function

• C1-set (PF07654)
• MHC_II_beta (PF00969)

Transmembrane Regions

228-250

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0052163|HLA class II histocompatibility antigen, DR beta 4 chain (HLA-DRB4)
ATGGTGTGTCTGAAGCTCCCTGGAGGCTCCTGTATGGCAGCGCTGACAGTGACATTGACG
GTGCTGAGCTCCCCACTGGCTTTGGCTGGGGACACCCAACCACGTTTCTTGGAGCAGGCT
AAGTGTGAGTGTCATTTCCTCAATGGGACGGAGCGAGTGTGGAACCTGATCAGATACATC
TATAACCAAGAGGAGTACGCGCGCTACAACAGTGACCTGGGGGAGTACCAGGCGGTGACG
GAGCTGGGGCGGCCTGACGCTGAGTACTGGAACAGCCAGAAGGACCTCCTGGAGCGGAGG
CGGGCCGAGGTGGACACCTACTGCAGATACAACTACGGGGTTGTGGAGAGCTTCACAGTG
CAGCGGCGAGTCCAACCTAAGGTGACTGTGTATCCTTCAAAGACCCAGCCCCTGCAGCAC
CACAACCTCCTGGTCTGCTCTGTGAATGGTTTCTATCCAGGCAGCATTGAAGTCAGGTGG
TTCCGGAACGGCCAGGAAGAGAAGGCTGGGGTGGTGTCCACAGGCCTGATCCAGAATGGA
GACTGGACCTTCCAGACCCTGGTGATGCTGGAAACAGTTCCTCGGAGTGGAGAGGTTTAC
ACCTGCCAAGTGGAGCATCCAAGCATGATGAGCCCTCTCACGGTGCAATGGAGTGCACGG
TCTGAATCTGCACAGAGCAAGATGCTGAGTGGAGTCGGGGGCTTTGTGCTGGGCCTGCTC
TTCCTTGGGACAGGGCTGTTCATCTACTTCAGGAATCAGAAAGGACACTCTGGACTTCAG
CCAACAGGACTCTTGAGCTGA

Chromosome Location

6

Locus

6p21.3

External Identifiers

Resource	Link
UniProtKB ID	P13762
UniProtKB Entry Name	DRB4_HUMAN
HGNC ID	HGNC:4952

General References

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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB05121	1D09C3	investigational	yes		Details
DB11294	Coccidioides immitis spherule	approved	unknown	binder	Details