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P20039 (2B1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
HLA class II histocompatibility antigen, DRB1-11 beta chain
Alternative name(s):
DR-5
Short name=DR5
DRw11
MHC class II antigen DRB1*11
Gene names
Name:HLA-DRB1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length266 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subunit structure

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.

Subcellular location

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. Ref.10

Post-translational modification

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II Probable. Ref.10

Polymorphism

The following alleles of DRB1-11 are known: DRB1*11:01, DRB1*11:03, DRB1*11:04, DRB1*11:05, DRB1*11:06, DRB1*11:07, DRB1*11:08, DRB1*11:09, DRB1*11:10, DRB1*11:11, DRB1*11:12, DRB1*11:13, DRB1*11:14, DRB1*11:15, DRB1*11:16, DRB1*11:17, DRB1*11:18, DRB1*11:19, DRB1*11:20, DRB1*11:21, DRB1*11:22, DRB1*11:23, DRB1*11:24, DRB1*11:25, DRB1*11:26, DRB1*11:27, DRB1*11:28, DRB1*11:29, DRB1*11:30, DRB1*11:31, DRB1*11:32, DRB1*11:33, DRB1*11:34, DRB1*11:35, DRB1*11:36, DRB1*11:37, DRB1*11:38, DRB1*11:39, DRB1*11:40, DRB1*11:41, DRB1*11:42, DRB1*11:43, DRB1*11:44, DRB1*11:45, DRB1*11:46, DRB1*11:47, DRB1*11:48, DRB1*11:49, DRB1*11:50, DRB1*11:51, DRB1*11:52, DRB1*11:53, DRB1*11:54, DRB1*11:55, DRB1*11:56, DRB1*11:57, DRB1*11:58, DRB1*11:59, DRB1*11:60, DRB1*11:61, DRB1*11:62, DRB1*11:63, DRB1*11:64, DRB1*11:65, DRB1*11:66, DRB1*11:67, DRB1*11:68, DRB1*11:69, DRB1*11:70 and DRB1*11:72. The sequence shown is that of DRB1*11:01.

Allele DRB1*11:01 is associated with self-limiting hepatitis C virus (HCV) infections [MIM:609532].

Sequence similarities

Belongs to the MHC class II family.

Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCell membrane
Endoplasmic reticulum
Endosome
Golgi apparatus
Lysosome
Membrane
MHC II
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell costimulation

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

antigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentER to Golgi transport vesicle membrane

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement. Source: Reactome

MHC class II protein complex

Inferred from electronic annotation. Source: UniProtKB-KW

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

integral component of lumenal side of endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

late endosome membrane

Inferred from direct assay Ref.10. Source: UniProtKB

lysosomal membrane

Inferred from direct assay Ref.10. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

trans-Golgi network membrane

Traceable author statement. Source: Reactome

transport vesicle membrane

Traceable author statement. Source: Reactome

   Molecular_functionMHC class II receptor activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929
Chain30 – 266237HLA class II histocompatibility antigen, DRB1-11 beta chain
PRO_0000018955

Regions

Topological domain30 – 227198Extracellular Potential
Transmembrane228 – 25023Helical; Potential
Topological domain251 – 26616Cytoplasmic Potential
Domain126 – 21489Ig-like C1-type
Region30 – 12495Beta-1
Region125 – 227103Beta-2

Amino acid modifications

Glycosylation481N-linked (GlcNAc...) Potential
Disulfide bond44 ↔ 108 By similarity
Disulfide bond146 ↔ 202 By similarity
Cross-link254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Natural variant551F → Y.
Corresponds to variant rs16822516 [ dbSNP | Ensembl ].
VAR_056542
Natural variant1001R → E in allele DRB1*11:03; requires 2 nucleotide substitutions.
VAR_016717
Natural variant1151G → V in allele DRB1*11:03 and allele DRB1*11:04.
VAR_016718
Natural variant2361V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
VAR_056543

Sequences

Sequence LengthMass (Da)Tools
P20039 [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 6CFC0D44391B1059

FASTA26630,160
        10         20         30         40         50         60 
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TSECHFFNGT ERVRFLDRYF 

        70         80         90        100        110        120 
YNQEEYVRFD SDVGEFRAVT ELGRPDEEYW NSQKDFLEDR RAAVDTYCRH NYGVGESFTV 

       130        140        150        160        170        180 
QRRVHPKVTV YPSKTQPLQH HNLLVCSVSG FYPGSIEVRW FRNGQEEKTG VVSTGLIHNG 

       190        200        210        220        230        240 
DWTFQTLVML ETVPRSGEVY TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL 

       250        260 
FLGAGLFIYF RNQKGHSGLQ PRGFLS 

« Hide

References

[1]"Complete characterization and sequence of an HLA class II DR beta chain cDNA from the DR5 haplotype."
Tieber V.L., Abruzzini L.F., Didier D.K., Schwartz B.D., Rotwein P.
J. Biol. Chem. 261:2738-2742(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*11:01).
[2]"A novel HLA-DR beta I sequence from the DRw11 haplotype."
Steimle V., Hinkkanen A., Schlesier M., Epplen J.T.
Immunogenetics 28:208-210(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DRB1*11:03).
[3]"Complete cDNA sequences of the HLA-DRB1*0402 and DRB1*11041 alleles."
Ramon D., Corell A., Cox S.T., Soteriou B., Madrigal J.A., Marsh S.G.E.
Eur. J. Immunogenet. 29:453-455(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*11:04).
[4]"HLA-DR beta-chain polymorphism. Second domain polymorphism reflects evolutionary relatedness of alleles and may explain public serologic epitopes."
Gorski J.
J. Immunol. 143:329-333(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-217.
[5]"Influence of MHC class II genotype on outcome of infection with hepatitis C virus."
Hepatitis C European Network for Cooperative Research
Thursz M., Yallop R., Goldin R., Trepo C., Thomas H.C.
Lancet 354:2119-2124(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH SUSCEPTIBILITY TO HEPATITIS C VIRUS.
[6]"Invariant chain structure and MHC class II function."
Cresswell P.
Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M11867 mRNA. Translation: AAA36274.1.
M22050 expand/collapse EMBL AC list , M21966, M22047, M22048, M22049 Genomic DNA. Translation: AAA59713.1.
AJ297587 mRNA. Translation: CAC08827.1.
PIRA25324.
F60748.
I54448.
PH0153.
UniGeneHs.534322.
Hs.696211.
Hs.736560.

3D structure databases

ProteinModelPortalP20039.
SMRP20039. Positions 34-220.
ModBaseSearch...
MobiDBSearch...

Polymorphism databases

DMDM122254.

Proteomic databases

PRIDEP20039.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328980; ENSP00000331343; ENSG00000206306.
ENST00000399450; ENSP00000382378; ENSG00000206240.

Organism-specific databases

GeneCardsGC06M032546.
GC06Mj32477.
GC06Mn32480.
HGNCHGNC:4948. HLA-DRB1.
MIM142857. gene.
609532. phenotype.
neXtProtNX_P20039.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG012730.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

CleanExHS_HLA-DRB1.
GenevestigatorP20039.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProIPR007110. 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]
PfamPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHLA-DRB1. human.
PROP20039.
SOURCESearch...

Entry information

Entry name2B1B_HUMAN
AccessionPrimary (citable) accession number: P20039
Secondary accession number(s): Q30006, Q9GIX8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM