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P13761 (2B17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. 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, DRB1-7 beta chain
Alternative name(s):
MHC class II antigen DRB1*7
Short name=DR-7
Short name=DR7
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.11

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.11

Polymorphism

The following alleles of DRB1-7 are known: DRB1*07:01, DRB1*07:03, DRB1*07:04, DRB1*07:05, DRB1*07:06, DRB1*07:07, DRB1*07:08, DRB1*07:09, DRB1*07:11, DRB1*07:12, DRB1*07:13, DRB1*07:14, DRB1*07:15, DRB1*07:16 and DRB1*07:17. The sequence shown is that of DRB1*07:01.

Allele DRB1*07:01 is associated with persistent 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

T-helper 1 type immune response

Inferred from mutant phenotype PubMed 15795121. Source: UniProtKB

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

detection of bacterium

Inferred from mutant phenotype PubMed 22321387. Source: UniProtKB

humoral immune response mediated by circulating immunoglobulin

Inferred from direct assay PubMed 17050030. Source: UniProtKB

immune response

Inferred from direct assay PubMed 20543955PubMed 21569485. Source: UniProtKB

immunoglobulin production involved in immunoglobulin mediated immune response

Inferred from direct assay PubMed 17050030. Source: UniProtKB

inflammatory response to antigenic stimulus

Inferred from direct assay PubMed 15795121. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

negative regulation of T cell proliferation

Inferred from mutant phenotype PubMed 15795121. Source: UniProtKB

negative regulation of interferon-gamma production

Inferred from mutant phenotype PubMed 15795121. Source: UniProtKB

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from mutant phenotype PubMed 21484216. Source: UniProtKB

protein tetramerization

Inferred from direct assay PubMed 20543955. Source: UniProtKB

regulation of interleukin-10 secretion

Inferred from direct assay PubMed 20543955. Source: UniProtKB

regulation of interleukin-4 production

Inferred from direct assay PubMed 20543955. Source: UniProtKB

   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

external side of plasma membrane

Inferred from direct assay PubMed 20543955. Source: UniProtKB

integral component of lumenal side of endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

late endosome membrane

Inferred from direct assay Ref.11. Source: UniProtKB

lysosomal membrane

Inferred from direct assay Ref.11. Source: UniProtKB

membrane

Traceable author statement Ref.5. 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.5. Source: UniProtKB

peptide antigen binding

Inferred from direct assay PubMed 20543955. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15795121. 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, DRB1-7 beta chain
PRO_0000018951

Regions

Topological domain30 – 227198Extracellular Potential
Transmembrane228 – 25023Helical; Potential
Topological domain251 – 26616Cytoplasmic Potential
Domain126 – 21691Ig-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) By similarity

Natural variations

Natural variant51K → R.
Corresponds to variant rs9270305 [ dbSNP | Ensembl ].
VAR_056532
Natural variant581R → S in allele DRB1*07:03.
VAR_016680
Natural variant1061T → N in allele DRB1*07:04.
VAR_016681
Natural variant1071V → Y in allele DRB1*07:04; requires 2 nucleotide substitutions.
VAR_016682
Natural variant2361V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
VAR_056533
Natural variant2621T → R.
Corresponds to variant rs9269744 [ dbSNP | Ensembl ].
VAR_056534

Sequences

Sequence LengthMass (Da)Tools
P13761 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: 439B6AFA553F162C

FASTA26629,822
        10         20         30         40         50         60 
MVCLKLPGGS CMAALTVTLM VLSSPLALAG DTQPRFLWQG KYKCHFFNGT ERVQFLERLF 

        70         80         90        100        110        120 
YNQEEFVRFD SDVGEYRAVT ELGRPVAESW NSQKDILEDR RGQVDTVCRH NYGVGESFTV 

       130        140        150        160        170        180 
QRRVHPEVTV YPAKTQPLQH HNLLVCSVSG FYPGSIEVRW FRNGQEEKAG VVSTGLIQNG 

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

       250        260 
FLGAGLFIYF RNQKGHSGLQ PTGFLS 

« Hide

References

« Hide 'large scale' references
[1]"Sequence and evolution of HLA-DR7- and -DRw53-associated beta-chain genes."
Young J.A.T., Wilkinson D., Bodmer W.F., Trowsdale J.
Proc. Natl. Acad. Sci. U.S.A. 84:4929-4933(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*07:01).
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB1*07:01).
Tissue: Lymph.
[4]"Identification of novel DR7, DRB5 and DQB1*03 alleles using the CANTYPE assay."
Buyse I.M., Couture C., Ouellet S., Hashemi-tavoularis S.
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-115 (ALLELE DRB1*07:03).
Tissue: Blood.
[5]"Molecular, serological and genetic studies on two new HLA-DRB1 alleles -- HLA-DRB1*0704 and HLA-DRB1*1507."
Darke C., Guttridge M.G., Street J., Thompson J., Thomas M.
Tissue Antigens 56:467-469(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-117 (ALLELE DRB1*07:04).
Tissue: Blood.
[6]"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.
[7]"Invariant chain structure and MHC class II function."
Cresswell P.
Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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
M16941 mRNA. Translation: AAA36282.1.
CR753309 Genomic DNA. Translation: CAQ07518.1.
CR753835 Genomic DNA. Translation: CAQ08239.1.
BC001023 mRNA. Translation: AAH01023.1.
Y13785 Genomic DNA. Translation: CAA74112.1.
Y16224 Genomic DNA. Translation: CAA76123.1.
PIRA28031.
UniGeneHs.696211.

3D structure databases

ProteinModelPortalP13761.
SMRP13761. Positions 32-219.
ModBaseSearch...
MobiDBSearch...

Polymorphism databases

DMDM122256.

Proteomic databases

PaxDbP13761.
PeptideAtlasP13761.
PRIDEP13761.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000437784; ENSP00000405960; ENSG00000229074.
ENST00000444645; ENSP00000409322; ENSG00000236884.
KEGGhsa:100507709.
hsa:100507714.
UCSCuc011gjy.2. human.

Organism-specific databases

GeneCardsGC06M032546.
GC06Mk32516.
GC06Ml32694.
HGNCHGNC:4948. HLA-DRB1.
MIM142857. gene.
609532. phenotype.
neXtProtNX_P13761.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68200.
HOVERGENHBG012730.
InParanoidP13761.
OMANGTERRY.
PhylomeDBP13761.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

CleanExHS_HLA-DRB1.
GenevestigatorP13761.

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.
NextBio34054816.
PROP13761.
SOURCESearch...

Entry information

Entry name2B17_HUMAN
AccessionPrimary (citable) accession number: P13761
Secondary accession number(s): B0UYW1, O46699, O46872
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 9, 2014
This is version 130 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