UniProtKB - P13762 (DRB4_HUMAN)
HLA class II histocompatibility antigen, DR beta 4 chain
HLA-DRB4
Functioni
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.
Caution
GO - Molecular functioni
- MHC class II protein complex binding Source: GO_Central
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- antigen processing and presentation of exogenous peptide antigen via MHC class II Source: GO_Central
- peptide antigen assembly with MHC class II protein complex Source: GO_Central
- positive regulation of T cell activation Source: GO_Central
Keywordsi
Biological process | Adaptive immunity, Immunity |
Enzyme and pathway databases
PathwayCommonsi | P13762 |
Reactomei | R-HSA-202424, Downstream TCR signaling R-HSA-202427, Phosphorylation of CD3 and TCR zeta chains R-HSA-202430, Translocation of ZAP-70 to Immunological synapse R-HSA-202433, Generation of second messenger molecules R-HSA-2132295, MHC class II antigen presentation R-HSA-389948, PD-1 signaling R-HSA-877300, Interferon gamma signaling |
SignaLinki | P13762 |
SIGNORi | P13762 |
Names & Taxonomyi
Protein namesi | Recommended name: HLA class II histocompatibility antigen, DR beta 4 chainAlternative name(s): MHC class II antigen DRB4 |
Gene namesi | Name:HLA-DRB4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4952, HLA-DRB4 |
neXtProti | NX_P13762 |
Subcellular locationi
Lysosome
Golgi apparatus
Endosome
Endoplasmic reticulum
Plasma membrane
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.
Endoplasmic reticulum
- integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
Endosome
- late endosome membrane Source: UniProtKB
Golgi apparatus
- Golgi membrane Source: Reactome
- trans-Golgi network membrane Source: Reactome
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- MHC class II protein complex Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- clathrin-coated endocytic vesicle membrane Source: Reactome
- endocytic vesicle membrane Source: Reactome
- ER to Golgi transport vesicle membrane Source: Reactome
- transport vesicle membrane Source: Reactome
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 30 – 227 | ExtracellularSequence analysisAdd BLAST | 198 | |
Transmembranei | 228 – 250 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 251 – 266 | CytoplasmicSequence analysisAdd BLAST | 16 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, MHC IIPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 254 | 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. 1 Publication | 1 | |
Mutagenesisi | 264 | L → A: Almost no change in down-regulation of MHC class II; when associated with A-265. 1 Publication | 1 | |
Mutagenesisi | 265 | L → A: Almost no change in down-regulation of MHC class II; when associated with A-264. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3126 |
OpenTargetsi | ENSG00000227357 |
PharmGKBi | PA35075 |
Miscellaneous databases
Pharosi | P13762, Tdark |
Chemistry databases
ChEMBLi | CHEMBL3988561 |
DrugBanki | DB05121, 1D09C3 DB11294, Coccidioides immitis spherule |
Genetic variation databases
BioMutai | HLA-DRB4 |
DMDMi | 281371554 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 29 | Add BLAST | 29 | |
ChainiPRO_0000018991 | 30 – 266 | HLA class II histocompatibility antigen, DR beta 4 chainAdd BLAST | 237 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 44 ↔ 108 | PROSITE-ProRule annotation | ||
Glycosylationi | 48 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 146 ↔ 202 | PROSITE-ProRule annotation | ||
Cross-linki | 254 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugationProteomic databases
jPOSTi | P13762 |
MassIVEi | P13762 |
PeptideAtlasi | P13762 |
PRIDEi | P13762 |
ProteomicsDBi | 52984 |
PTM databases
GlyGeni | P13762, 1 site |
iPTMneti | P13762 |
PhosphoSitePlusi | P13762 |
Interactioni
Subunit structurei
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.
Protein-protein interaction databases
BioGRIDi | 109371, 10 interactors |
IntActi | P13762, 1 interactor |
Miscellaneous databases
RNActi | P13762, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 126 – 216 | Ig-like C1-typeAdd BLAST | 91 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 30 – 124 | Beta-1Add BLAST | 95 | |
Regioni | 125 – 227 | Beta-2Add BLAST | 103 |
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
InParanoidi | P13762 |
OMAi | GHIEVTW |
OrthoDBi | 1249505at2759 |
PhylomeDBi | P13762 |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit 3.10.320.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf 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 IPR000353, MHC_II_b_N |
Pfami | View protein in Pfam PF07654, C1-set, 1 hit PF00969, MHC_II_beta, 1 hit |
SMARTi | View protein in SMART SM00407, IGc1, 1 hit SM00921, MHC_II_beta, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit SSF54452, SSF54452, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit PS00290, IG_MHC, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MVCLKLPGGS CMAALTVTLT VLSSPLALAG DTQPRFLEQA KCECHFLNGT
60 70 80 90 100
ERVWNLIRYI YNQEEYARYN SDLGEYQAVT ELGRPDAEYW NSQKDLLERR
110 120 130 140 150
RAEVDTYCRY NYGVVESFTV QRRVQPKVTV YPSKTQPLQH HNLLVCSVNG
160 170 180 190 200
FYPGSIEVRW FRNGQEEKAG VVSTGLIQNG DWTFQTLVML ETVPRSGEVY
210 220 230 240 250
TCQVEHPSMM SPLTVQWSAR SESAQSKMLS GVGGFVLGLL FLGTGLFIYF
260
RNQKGHSGLQ PTGLLS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketX5D2U9 | X5D2U9_HUMAN | HLA class II histocompatibility ant... | HLA-DRB4 | 266 | Annotation score: | ||
A0A0G2JJQ8 | A0A0G2JJQ8_HUMAN | HLA class II histocompatibility ant... | HLA-DRB4 | 266 | Annotation score: |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_060778 | 105 | D → G in allele DRB4*01:02. | 1 | |
Natural variantiVAR_060779 | 106 | T → N in allele DRB4*01:04. | 1 | |
Natural variantiVAR_060780 | 110 | Y → H in allele DRB4*01:05. | 1 | |
Natural variantiVAR_060781 | 113 | G → R in allele DRB4*01:07. | 1 | |
Natural variantiVAR_060782 | 141 | H → Y in allele DRB4*01:06. | 1 | |
Natural variantiVAR_060783 | 164 | G → S in allele DRB4*01:01 and allele DRB4*01:06. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M16942 mRNA Translation: AAA36296.1 AF361548 mRNA Translation: AAM00252.1 AF361549 mRNA Translation: AAM00253.1 DQ284431 mRNA Translation: ABC66198.1 GQ891550 mRNA Translation: ACX50637.1 AK292151 mRNA Translation: BAF84840.1 BX571807 Genomic DNA No translation available. BX120007 Genomic DNA No translation available. BX927235 Genomic DNA No translation available. CR788250 Genomic DNA No translation available. BC005312 mRNA Translation: AAH05312.1 M15178 mRNA Translation: AAA35995.1 M20555 Genomic DNA Translation: AAA59830.1 AH012539 Genomic DNA Translation: AAO43051.1 AH011268 Genomic DNA Translation: AAL48256.1 AB107960 Genomic DNA Translation: BAC75547.1 Y09313 Genomic DNA Translation: CAA70497.1 AY394720 Genomic DNA Translation: AAQ96922.1 |
PIRi | B28031 I59092 PT0168 |
RefSeqi | NP_068818.4, NM_021983.4 XP_016885779.1, XM_017030290.1 |
Genome annotation databases
Ensembli | ENST00000411565; ENSP00000410857; ENSG00000227357 ENST00000457451; ENSP00000412031; ENSG00000231021 |
GeneIDi | 3126 |
KEGGi | hsa:3126 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M16942 mRNA Translation: AAA36296.1 AF361548 mRNA Translation: AAM00252.1 AF361549 mRNA Translation: AAM00253.1 DQ284431 mRNA Translation: ABC66198.1 GQ891550 mRNA Translation: ACX50637.1 AK292151 mRNA Translation: BAF84840.1 BX571807 Genomic DNA No translation available. BX120007 Genomic DNA No translation available. BX927235 Genomic DNA No translation available. CR788250 Genomic DNA No translation available. BC005312 mRNA Translation: AAH05312.1 M15178 mRNA Translation: AAA35995.1 M20555 Genomic DNA Translation: AAA59830.1 AH012539 Genomic DNA Translation: AAO43051.1 AH011268 Genomic DNA Translation: AAL48256.1 AB107960 Genomic DNA Translation: BAC75547.1 Y09313 Genomic DNA Translation: CAA70497.1 AY394720 Genomic DNA Translation: AAQ96922.1 |
PIRi | B28031 I59092 PT0168 |
RefSeqi | NP_068818.4, NM_021983.4 XP_016885779.1, XM_017030290.1 |
3D structure databases
SMRi | P13762 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109371, 10 interactors |
IntActi | P13762, 1 interactor |
Chemistry databases
ChEMBLi | CHEMBL3988561 |
DrugBanki | DB05121, 1D09C3 DB11294, Coccidioides immitis spherule |
PTM databases
GlyGeni | P13762, 1 site |
iPTMneti | P13762 |
PhosphoSitePlusi | P13762 |
Genetic variation databases
BioMutai | HLA-DRB4 |
DMDMi | 281371554 |
Proteomic databases
jPOSTi | P13762 |
MassIVEi | P13762 |
PeptideAtlasi | P13762 |
PRIDEi | P13762 |
ProteomicsDBi | 52984 |
Protocols and materials databases
DNASUi | 3126 |
Genome annotation databases
Ensembli | ENST00000411565; ENSP00000410857; ENSG00000227357 ENST00000457451; ENSP00000412031; ENSG00000231021 |
GeneIDi | 3126 |
KEGGi | hsa:3126 |
Organism-specific databases
CTDi | 3126 |
DisGeNETi | 3126 |
GeneCardsi | HLA-DRB4 |
HGNCi | HGNC:4952, HLA-DRB4 |
neXtProti | NX_P13762 |
OpenTargetsi | ENSG00000227357 |
PharmGKBi | PA35075 |
GenAtlasi | Search... |
Phylogenomic databases
InParanoidi | P13762 |
OMAi | GHIEVTW |
OrthoDBi | 1249505at2759 |
PhylomeDBi | P13762 |
Enzyme and pathway databases
PathwayCommonsi | P13762 |
Reactomei | R-HSA-202424, Downstream TCR signaling R-HSA-202427, Phosphorylation of CD3 and TCR zeta chains R-HSA-202430, Translocation of ZAP-70 to Immunological synapse R-HSA-202433, Generation of second messenger molecules R-HSA-2132295, MHC class II antigen presentation R-HSA-389948, PD-1 signaling R-HSA-877300, Interferon gamma signaling |
SignaLinki | P13762 |
SIGNORi | P13762 |
Miscellaneous databases
BioGRID-ORCSi | 3126, 0 hits in 1 CRISPR screen |
GeneWikii | HLA-DRB4 |
GenomeRNAii | 3126 |
Pharosi | P13762, Tdark |
PROi | PR:P13762 |
RNActi | P13762, protein |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit 3.10.320.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf 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 IPR000353, MHC_II_b_N |
Pfami | View protein in Pfam PF07654, C1-set, 1 hit PF00969, MHC_II_beta, 1 hit |
SMARTi | View protein in SMART SM00407, IGc1, 1 hit SM00921, MHC_II_beta, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit SSF54452, SSF54452, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit PS00290, IG_MHC, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DRB4_HUMAN | |
Accessioni | P13762Primary (citable) accession number: P13762 Secondary accession number(s): B0S863 Q9BS54 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | December 15, 2009 | |
Last modified: | February 23, 2022 | |
This is version 156 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - SIMILARITY comments
Index of protein domains and families