SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P01912

- 2B13_HUMAN

UniProt

P01912 - 2B13_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

HLA class II histocompatibility antigen, DRB1-3 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 - Molecular functioni

  1. peptide antigen binding Source: UniProt

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. humoral immune response mediated by circulating immunoglobulin Source: UniProtKB
  4. immunoglobulin production involved in immunoglobulin mediated immune response Source: UniProtKB
  5. interferon-gamma-mediated signaling pathway Source: Reactome
  6. peptide antigen assembly with MHC class II protein complex Source: UniProt
  7. T cell costimulation Source: Reactome
  8. 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, DRB1-3 chain
Alternative name(s):
Clone P2-beta-3
MHC class II antigen DRB1*3
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:4948. HLA-DRB1.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatustrans-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.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini30 – 227198Extracellular Reviewed predictionAdd
BLAST
Transmembranei228 – 25023Helical; Reviewed predictionAdd
BLAST
Topological domaini251 – 26616Cytoplasmic Reviewed predictionAdd
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: UniProt
  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, DRB1-3 chainPRO_0000018965Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 1081 Publication
Glycosylationi48 – 481N-linked (GlcNAc...)1 Publication
Disulfide bondi146 ↔ 2021 Publication
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 Inferred.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiP01912.

Expressioni

Gene expression databases

CleanExiHS_HLA-DRB1.
GenevestigatoriP01912.

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.1 Publication

Protein-protein interaction databases

BioGridi109368. 15 interactions.
DIPiDIP-6064N.
IntActiP01912. 8 interactions.
MINTiMINT-1505391.

Structurei

Secondary structure

1
266
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi37 – 4711
Turni48 – 514
Beta strandi52 – 6110
Beta strandi64 – 707
Turni71 – 733
Beta strandi75 – 806
Helixi81 – 833
Helixi84 – 929
Helixi94 – 1018
Helixi103 – 1064
Helixi108 – 1158
Turni116 – 1216
Beta strandi127 – 1348
Beta strandi138 – 1403
Beta strandi143 – 1508
Beta strandi152 – 1543
Beta strandi157 – 1626
Beta strandi180 – 1823
Beta strandi184 – 1874
Beta strandi189 – 1913
Beta strandi199 – 2057
Beta strandi213 – 2186

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6AX-ray2.75B34-220[»]
ProteinModelPortaliP01912.
SMRiP01912. Positions 34-220.

Miscellaneous databases

EvolutionaryTraceiP01912.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini126 – 21489Ig-like C1-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 12394Beta-1Add
BLAST
Regioni124 – 21794Beta-2Add
BLAST
Regioni218 – 22710Connecting peptide

Sequence similaritiesi

Belongs to the MHC class II family.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG012730.
KOiK06752.
OMAiNGMERVR.
PhylomeDBiP01912.

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.

P01912-1 [UniParc]FASTAAdd to Basket

« Hide

MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TSECHFFNGT    50
ERVRYLDRYF HNQEENVRFD SDVGEFRAVT ELGRPDAEYW NSQKDLLEQK 100
RGRVDNYCRH NYGVVESFTV QRRVHPKVTV YPSKTQPLQH HNLLVCSVSG 150
FYPGSIEVRW FRNGQEEKTG VVSTGLIHNG DWTFQTLVML ETVPRSGEVY 200
TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF 250
RNQKGHSGLQ PRGFLS 266
Length:266
Mass (Da):30,120
Last modified:October 1, 1996 - v2
Checksum:i37329B097C6BEEB4
GO

Polymorphismi

The following alleles of DRB1-3 are known: DRB1*03:01; DRB1*03:02; DRB1*03:03; DRB1*03:04; DRB1*03:05; DRB1*03:06; DRB1*03:07; DRB1*03:08; DRB1*03:09; DRB1*03:10; DRB1*03:11; DRB1*03:12; DRB1*03:13; DRB1*03:14; DRB1*03:15; DRB1*03:16; DRB1*03:17; DRB1*03:18; DRB1*03:19; DRB1*03:20; DRB1*03:21; DRB1*03:22; DRB1*03:23; DRB1*03:24; DRB1*03:25; DRB1*03:26; DRB1*03:27; DRB1*03:28; DRB1*03:29; DRB1*03:30; DRB1*03:31; DRB1*03:32; DRB1*03:33; DRB1*03:34; DRB1*03:35; DRB1*03:36; DRB1*03:37; DRB1*03:38; DRB1*03:39; DRB1*03:40 and DRB1*03:41. The sequence shown is that of DRB1*03:01.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551Y → F.
Corresponds to variant rs16822516 [ dbSNP | Ensembl ].
VAR_050371
Natural varianti106 – 1061N → T.
Corresponds to variant rs9269941 [ dbSNP | Ensembl ].
VAR_050372
Natural varianti164 – 1641G → S.
Corresponds to variant rs1059633 [ dbSNP | Ensembl ].
VAR_050373
Natural varianti169 – 1691T → A.
Corresponds to variant rs2308768 [ dbSNP | Ensembl ].
VAR_050374
Natural varianti236 – 2361V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
VAR_056545

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X00699 mRNA. Translation: CAA25295.1.
PIRiI37546. HLHU3D.
RefSeqiNP_001230894.1. NM_001243965.1.
UniGeneiHs.534322.
Hs.696211.
Hs.736560.

Genome annotation databases

EnsembliENST00000328980; ENSP00000331343; ENSG00000206306.
ENST00000399450; ENSP00000382378; ENSG00000206240.
GeneIDi3123.
KEGGihsa:3123.
UCSCiuc011eri.2. human.

Polymorphism databases

DMDMi1708116.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X00699 mRNA. Translation: CAA25295.1 .
PIRi I37546. HLHU3D.
RefSeqi NP_001230894.1. NM_001243965.1.
UniGenei Hs.534322.
Hs.696211.
Hs.736560.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A6A X-ray 2.75 B 34-220 [» ]
ProteinModelPortali P01912.
SMRi P01912. Positions 34-220.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109368. 15 interactions.
DIPi DIP-6064N.
IntActi P01912. 8 interactions.
MINTi MINT-1505391.

Polymorphism databases

DMDMi 1708116.

Proteomic databases

PRIDEi P01912.

Protocols and materials databases

DNASUi 3123.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000328980 ; ENSP00000331343 ; ENSG00000206306 .
ENST00000399450 ; ENSP00000382378 ; ENSG00000206240 .
GeneIDi 3123.
KEGGi hsa:3123.
UCSCi uc011eri.2. human.

Organism-specific databases

CTDi 3123.
GeneCardsi GC06M032546.
GC06Mj32477.
GC06Mn32480.
HGNCi HGNC:4948. HLA-DRB1.
MIMi 142857. gene.
neXtProti NX_P01912.
GenAtlasi Search...

Phylogenomic databases

HOVERGENi HBG012730.
KOi K06752.
OMAi NGMERVR.
PhylomeDBi P01912.

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.
EvolutionaryTracei P01912.
GenomeRNAii 3123.
NextBioi 12394.
SOURCEi Search...

Gene expression databases

CleanExi HS_HLA-DRB1.
Genevestigatori P01912.

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

« Hide 'large scale' publications
  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*03:01).
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-266 (ALLELE DRB1*03:01).
  3. "Invariant chain structure and MHC class II function."
    Cresswell P.
    Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "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.
  5. "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.
  6. "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.
  7. "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.
  8. "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.
  9. "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.
  10. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48.
    Tissue: Liver.
  11. "The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3."
    Ghosh P., Amaya M., Mellins E., Wiley D.C.
    Nature 378:457-462(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-220 OF HLA-DRA/HLA-DRB1 HETERODIMER IN COMPLEX WITH CD74 PEPTIDE (CLIP), SUBUNIT, DISULFIDE BONDS.

Entry informationi

Entry namei2B13_HUMAN
AccessioniPrimary (citable) accession number: P01912
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 131 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi