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Protein

HLA class II histocompatibility antigen, DRB1-15 beta chain

Gene

HLA-DRB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.

GO - Molecular functioni

  • MHC class II protein complex binding Source: UniProtKB
  • peptide antigen binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity

Enzyme and pathway databases

BioCyciZFISH:G66-31507-MONOMER.
ReactomeiR-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.

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DRB1-15 beta chain
Alternative name(s):
DW2.2/DR2.2
MHC class II antigen DRB1*15
Gene namesi
Name:HLA-DRB1
Synonyms:HLA-DRB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4948. HLA-DRB1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 227ExtracellularSequence analysisAdd BLAST198
Transmembranei228 – 248HelicalSequence analysisAdd BLAST21
Topological domaini249 – 266CytoplasmicSequence analysisAdd BLAST18

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • clathrin-coated endocytic vesicle membrane Source: Reactome
  • endocytic vesicle membrane Source: Reactome
  • ER to Golgi transport vesicle membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • Golgi membrane Source: Reactome
  • integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
  • late endosome membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • MHC class II protein complex Source: UniProtKB
  • plasma membrane Source: Reactome
  • trans-Golgi network membrane Source: Reactome
  • transport vesicle membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, MHC II

Pathology & Biotechi

Organism-specific databases

DisGeNETi3123.
MalaCardsiHLA-DRB1.
OpenTargetsiENSG00000196126.
PharmGKBiPA35072.

Polymorphism and mutation databases

BioMutaiATXN1.
DMDMi166214928.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 292 PublicationsAdd BLAST29
ChainiPRO_000008074430 – 266HLA class II histocompatibility antigen, DRB1-15 beta chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 108
Glycosylationi48N-linked (GlcNAc...)1
Disulfide bondi146 ↔ 202
Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiP01911.
PeptideAtlasiP01911.
PRIDEiP01911.

PTM databases

iPTMnetiP01911.

Expressioni

Gene expression databases

BgeeiENSG00000196126.
CleanExiHS_HLA-DRB1.
ExpressionAtlasiP01911. baseline and differential.
GenevisibleiP01911. HS.

Organism-specific databases

HPAiCAB015400.
CAB034021.

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.

GO - Molecular functioni

  • MHC class II protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109368. 38 interactors.
IntActiP01911. 1 interactor.
STRINGi9606.ENSP00000353099.

Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi36 – 47Combined sources12
Turni48 – 51Combined sources4
Beta strandi52 – 61Combined sources10
Beta strandi64 – 70Combined sources7
Turni71 – 73Combined sources3
Beta strandi75 – 80Combined sources6
Helixi81 – 83Combined sources3
Helixi84 – 92Combined sources9
Helixi94 – 106Combined sources13
Helixi108 – 115Combined sources8
Turni116 – 121Combined sources6
Beta strandi127 – 134Combined sources8
Beta strandi142 – 154Combined sources13
Beta strandi157 – 162Combined sources6
Beta strandi165 – 167Combined sources3
Beta strandi169 – 173Combined sources5
Beta strandi180 – 182Combined sources3
Beta strandi184 – 192Combined sources9
Beta strandi199 – 205Combined sources7
Beta strandi209 – 211Combined sources3
Beta strandi213 – 218Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BX2X-ray2.60B/E32-222[»]
1YMMX-ray3.50B30-227[»]
2WBJX-ray3.00B/F30-227[»]
ProteinModelPortaliP01911.
SMRiP01911.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01911.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 214Ig-like C1-typeAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 124Beta-1Add BLAST95
Regioni125 – 227Beta-2Add BLAST103

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWG3. Eukaryota.
ENOG410YI0S. LUCA.
GeneTreeiENSGT00760000118970.
HOVERGENiHBG012730.
InParanoidiP01911.
PhylomeDBiP01911.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiIPR007110. 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.
IPR000353. MHC_II_b_N.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomiPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01911-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVCLKLPGGS CMTALTVTLM VLSSPLALSG DTRPRFLWQP KRECHFFNGT
60 70 80 90 100
ERVRFLDRYF YNQEESVRFD SDVGEFRAVT ELGRPDAEYW NSQKDILEQA
110 120 130 140 150
RAAVDTYCRH NYGVVESFTV QRRVQPKVTV YPSKTQPLQH HNLLVCSVSG
160 170 180 190 200
FYPGSIEVRW FLNGQEEKAG MVSTGLIQNG DWTFQTLVML ETVPRSGEVY
210 220 230 240 250
TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF
260
RNQKGHSGLQ PTGFLS
Length:266
Mass (Da):29,966
Last modified:January 15, 2008 - v2
Checksum:i3B5912820A4654BE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119T → A in AAI08923 (PubMed:15489334).Curated1
Sequence conflicti154G → A in AAA59801 (PubMed:3476943).Curated1
Sequence conflicti171M → G AA sequence (PubMed:6947956).Curated1
Sequence conflicti179 – 180NG → D AA sequence (PubMed:6947956).Curated2

Polymorphismi

The following alleles of DRB1-15 are known: DRB1*15:01, DRB1*15:02, DRB1*15:03, DRB1*15:04, DRB1*15:05, DRB1*15:06, DRB1*15:07, DRB1*15:08, DRB1*15:09, DRB1*15:10, DRB1*15:11, DRB1*15:12, DRB1*15:13, DRB1*15:14, DRB1*15:15, DRB1*15:16, DRB1*15:18, DRB1*15:19, DRB1*15:20, DRB1*15:21, DRB1*15:22, DRB1*15:23, DRB1*15:24, DRB1*15:25, DRB1*15:26, DRB1*15:27, DRB1*15:28, DRB1*15:29, DRB1*15:30, DRB1*15:31 and DRB1*15:32. The sequence shown is that of DRB1*15:01.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0503645K → R.Corresponds to variant rs9270305dbSNPEnsembl.1
Natural variantiVAR_05036555F → Y.Corresponds to variant rs16822516dbSNPEnsembl.1
Natural variantiVAR_03816259Y → H in allele DRB1*15:03. Corresponds to variant rs11554462dbSNPEnsembl.1
Natural variantiVAR_03816396I → F in allele DRB1*15:04. Corresponds to variant rs17886918dbSNPEnsembl.1
Natural variantiVAR_050366106T → N.Corresponds to variant rs9269941dbSNPEnsembl.1
Natural variantiVAR_038164115V → G in allele DRB1*15:02. Corresponds to variant rs17885482dbSNPEnsembl.1
Natural variantiVAR_050367164G → S.Corresponds to variant rs1059633dbSNPEnsembl.1
Natural variantiVAR_050368169A → T.Corresponds to variant rs2308768dbSNPEnsembl.1
Natural variantiVAR_050369236V → M.Corresponds to variant rs2230816dbSNPEnsembl.1
Natural variantiVAR_050370262T → R.Corresponds to variant rs9269744dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20430 mRNA. Translation: AAA59831.1.
AY663395 Genomic DNA. Translation: AAU87979.1.
AY663406 Genomic DNA. Translation: AAU88008.1.
AY663411 Genomic DNA. Translation: AAU88023.1.
AY663414 Genomic DNA. Translation: AAU88033.1.
AY961072 mRNA. Translation: AAX63460.1.
AY961073 mRNA. Translation: AAX63461.1.
AL713966 Genomic DNA. Translation: CAI18081.1.
BC033827 mRNA. Translation: AAH33827.1.
BC108922 mRNA. Translation: AAI08923.1.
M28584 mRNA. Translation: AAA59681.1.
M16957 mRNA. Translation: AAA36279.1.
M17378 mRNA. Translation: AAA59801.1.
CCDSiCCDS47409.1.
PIRiI68734. HLHUWB.
RefSeqiNP_002115.2. NM_002124.3.
UniGeneiHs.534322.
Hs.696211.
Hs.736560.

Genome annotation databases

EnsembliENST00000360004; ENSP00000353099; ENSG00000196126.
GeneIDi3123.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20430 mRNA. Translation: AAA59831.1.
AY663395 Genomic DNA. Translation: AAU87979.1.
AY663406 Genomic DNA. Translation: AAU88008.1.
AY663411 Genomic DNA. Translation: AAU88023.1.
AY663414 Genomic DNA. Translation: AAU88033.1.
AY961072 mRNA. Translation: AAX63460.1.
AY961073 mRNA. Translation: AAX63461.1.
AL713966 Genomic DNA. Translation: CAI18081.1.
BC033827 mRNA. Translation: AAH33827.1.
BC108922 mRNA. Translation: AAI08923.1.
M28584 mRNA. Translation: AAA59681.1.
M16957 mRNA. Translation: AAA36279.1.
M17378 mRNA. Translation: AAA59801.1.
CCDSiCCDS47409.1.
PIRiI68734. HLHUWB.
RefSeqiNP_002115.2. NM_002124.3.
UniGeneiHs.534322.
Hs.696211.
Hs.736560.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BX2X-ray2.60B/E32-222[»]
1YMMX-ray3.50B30-227[»]
2WBJX-ray3.00B/F30-227[»]
ProteinModelPortaliP01911.
SMRiP01911.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109368. 38 interactors.
IntActiP01911. 1 interactor.
STRINGi9606.ENSP00000353099.

PTM databases

iPTMnetiP01911.

Polymorphism and mutation databases

BioMutaiATXN1.
DMDMi166214928.

Proteomic databases

PaxDbiP01911.
PeptideAtlasiP01911.
PRIDEiP01911.

Protocols and materials databases

DNASUi3123.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360004; ENSP00000353099; ENSG00000196126.
GeneIDi3123.

Organism-specific databases

CTDi3123.
DisGeNETi3123.
GeneCardsiHLA-DRB1.
HGNCiHGNC:4948. HLA-DRB1.
HPAiCAB015400.
CAB034021.
MalaCardsiHLA-DRB1.
MIMi142857. gene.
neXtProtiNX_P01911.
OpenTargetsiENSG00000196126.
PharmGKBiPA35072.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWG3. Eukaryota.
ENOG410YI0S. LUCA.
GeneTreeiENSGT00760000118970.
HOVERGENiHBG012730.
InParanoidiP01911.
PhylomeDBiP01911.

Enzyme and pathway databases

BioCyciZFISH:G66-31507-MONOMER.
ReactomeiR-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.

Miscellaneous databases

ChiTaRSiHLA-DRB1. human.
EvolutionaryTraceiP01911.
GeneWikiiHLA-DRB1.
GenomeRNAii3123.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196126.
CleanExiHS_HLA-DRB1.
ExpressionAtlasiP01911. baseline and differential.
GenevisibleiP01911. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiIPR007110. 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.
IPR000353. MHC_II_b_N.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomiPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei2B1F_HUMAN
AccessioniPrimary (citable) accession number: P01911
Secondary accession number(s): Q29790
, Q29975, Q30142, Q30166, Q32MY7, Q56FN9, Q5Y7B0, Q5Y7B9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 15, 2008
Last modified: November 2, 2016
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

The chain shown constituted about 70% of a pool of at least seven similar beta chains.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.