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Q30167

- 2B1A_HUMAN

UniProt

Q30167 - 2B1A_HUMAN

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Protein

HLA class II histocompatibility antigen, DRB1-10 beta chain

Gene

HLA-DRB1

Organism
Homo sapiens (Human)
Status
Reviewed - 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 - Biological processi

  1. antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  2. cytokine-mediated signaling pathway Source: Reactome
  3. interferon-gamma-mediated signaling pathway Source: Reactome
  4. T cell costimulation Source: Reactome
  5. T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Immunity

Enzyme and pathway databases

ReactomeiREACT_121399. MHC class II antigen presentation.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_19324. PD-1 signaling.
REACT_25078. Interferon gamma signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DRB1-10 beta chain
Alternative name(s):
DRw10
MHC class II antigen DRB1*10
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:4948. HLA-DRB1.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Endoplasmic reticulum membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Golgi apparatustrans-Golgi network membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Endosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Lysosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Late endosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication
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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini30 – 227198ExtracellularSequence AnalysisAdd
BLAST
Transmembranei228 – 25023HelicalSequence AnalysisAdd
BLAST
Topological domaini251 – 26616CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. clathrin-coated endocytic vesicle membrane Source: Reactome
  2. endocytic vesicle membrane Source: Reactome
  3. ER to Golgi transport vesicle membrane Source: Reactome
  4. Golgi membrane Source: Reactome
  5. integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
  6. late endosome membrane Source: UniProtKB
  7. lysosomal membrane Source: UniProtKB
  8. MHC class II protein complex Source: UniProtKB-KW
  9. plasma membrane Source: Reactome
  10. trans-Golgi network membrane Source: Reactome
  11. transport vesicle membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Add
BLAST
Chaini30 – 266237HLA class II histocompatibility antigen, DRB1-10 beta chainPRO_0000018954Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 108PROSITE-ProRule annotation
Glycosylationi48 – 481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi146 ↔ 202PROSITE-ProRule annotation
Cross-linki254 – 254Glycyl 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

PRIDEiQ30167.

Expressioni

Gene expression databases

CleanExiHS_HLA-DRB1.
GenevestigatoriQ30167.

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.

Structurei

3D structure databases

ProteinModelPortaliQ30167.
SMRiQ30167. Positions 30-219.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini126 – 21691Ig-like C1-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 12495Beta-1Add
BLAST
Regioni125 – 227103Beta-2Add
BLAST

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG012730.

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]
SUPFAMiSSF54452. 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.

Q30167-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEEV KFECHFFNGT
60 70 80 90 100
ERVRLLERRV HNQEEYARYD SDVGEYRAVT ELGRPDAEYW NSQKDLLERR
110 120 130 140 150
RAAVDTYCRH NYGVGESFTV QRRVQPKVTV YPSKTQPLQH HNLLVCSVNG
160 170 180 190 200
FYPGSIEVRW FRNGQEEKTG VVSTGLIQNG DWTFQTLVML ETVPQSGEVY
210 220 230 240 250
TCQVEHPSVM SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF
260
RNQKGHSGLP PTGFLS
Length:266
Mass (Da):30,002
Last modified:March 23, 2010 - v2
Checksum:i45AB410F8AC21750
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801G → E in AAA59832. (PubMed:2450924)Curated

Polymorphismi

The following alleles of DRB1-10 are known: DRB1*10:01; DRB1*10:02 and DRB1*10:03. The sequence shown is that of DRB1*10:01.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti236 – 2361V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
VAR_056540
Natural varianti262 – 2621T → R.
Corresponds to variant rs9269744 [ dbSNP | Ensembl ].
VAR_056541

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00700 mRNA. Translation: CAA25296.1.
M20138 mRNA. Translation: AAA59832.1.
AF225565 Genomic DNA. Translation: AAF65542.1.
PIRiA27614. HLHU4D.
UniGeneiHs.534322.
Hs.696211.
Hs.736560.

Genome annotation databases

EnsembliENST00000419393; ENSP00000403458; ENSG00000228080.

Polymorphism databases

DMDMi292494999.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00700 mRNA. Translation: CAA25296.1 .
M20138 mRNA. Translation: AAA59832.1 .
AF225565 Genomic DNA. Translation: AAF65542.1 .
PIRi A27614. HLHU4D.
UniGenei Hs.534322.
Hs.696211.
Hs.736560.

3D structure databases

ProteinModelPortali Q30167.
SMRi Q30167. Positions 30-219.
ModBasei Search...
MobiDBi Search...

Polymorphism databases

DMDMi 292494999.

Proteomic databases

PRIDEi Q30167.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000419393 ; ENSP00000403458 ; ENSG00000228080 .

Organism-specific databases

GeneCardsi GC06M032546.
GC06Mo32637.
HGNCi HGNC:4948. HLA-DRB1.
MIMi 142857. gene.
neXtProti NX_Q30167.
GenAtlasi Search...

Phylogenomic databases

HOVERGENi HBG012730.

Enzyme and pathway databases

Reactomei REACT_121399. MHC class II antigen presentation.
REACT_12555. Downstream TCR signaling.
REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
REACT_12596. Translocation of ZAP-70 to Immunological synapse.
REACT_12623. Generation of second messenger molecules.
REACT_19324. PD-1 signaling.
REACT_25078. Interferon gamma signaling.

Miscellaneous databases

ChiTaRSi HLA-DRB1. human.
PROi Q30167.
SOURCEi Search...

Gene expression databases

CleanExi HS_HLA-DRB1.
Genevestigatori Q30167.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProi IPR007110. 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 ]
Pfami PF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view ]
ProDomi PD000328. MHC_II_b_N. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SMARTi SM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view ]
SUPFAMi SSF54452. SSF54452. 1 hit.
PROSITEi PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Mutations and selection in the generation of class II histocompatibility antigen polymorphism."
    Peterson P.A., Gustafsson K., Wiman K.G., Emmoth E., Larhammar D., Boehme J., Hyldig-Nielsen J.J., Ronne H., Rask L.
    EMBO J. 3:1655-1660(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*10:01).
  2. "Nucleotide sequence of a DRw10 beta chain cDNA clone. Identity of the third D region with that of the DRw53 allele of the beta 2 locus and as the probable site encoding a polymorphic MHC class II epitope."
    Merryman P., Gregersen P.K., Lee S., Silver J., Nunez-Roldan A., Crapper R., Winchester R.
    J. Immunol. 140:2447-2452(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*10:01).
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-266 (ALLELE DRB1*10:01).
  4. "Sequence of an HLA-DRB gene."
    Woelpl A.
    Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*10:01).
  5. "Invariant chain structure and MHC class II function."
    Cresswell P.
    Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "Presentation of antigens by MHC class II molecules: getting the most out of them."
    Villadangos J.A.
    Mol. Immunol. 38:329-346(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. "Autophagy in MHC class II presentation: sampling from within."
    Menendez-Benito V., Neefjes J.
    Immunity 26:1-3(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. "MHC class II molecules on the move for successful antigen presentation."
    Rocha N., Neefjes J.
    EMBO J. 27:1-5(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  9. "MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation."
    De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P., Gatti E.
    Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION BY MARCH1, SUBCELLULAR LOCATION.
  10. "MHC class II transport at a glance."
    Berger A.C., Roche P.A.
    J. Cell Sci. 122:1-4(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  11. "CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract."
    Beswick E.J., Reyes V.E.
    World J. Gastroenterol. 15:2855-2861(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry namei2B1A_HUMAN
AccessioniPrimary (citable) accession number: Q30167
Secondary accession number(s): P01914, Q9MYF5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: March 23, 2010
Last modified: October 29, 2014
This is version 107 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

Keywords - Technical termi

Complete proteome, 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3