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Q30134

- 2B18_HUMAN

UniProt

Q30134 - 2B18_HUMAN

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Protein

HLA class II histocompatibility antigen, DRB1-8 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, DRB1-8 beta chain
Alternative name(s):
MHC class II antigen DRB1*8
Short name:
DR-8
Short name:
DR8
Short name:
DRw8
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.

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, DRB1-8 beta chainPRO_0000018952Add
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

PaxDbiQ30134.
PRIDEiQ30134.

Expressioni

Gene expression databases

CleanExiHS_HLA-DRB1.
GenevestigatoriQ30134.

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

ProteinModelPortaliQ30134.
SMRiQ30134. Positions 34-220.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

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

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei228 – 25023HelicalSequence AnalysisAdd
BLAST

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 – 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

eggNOGiNOG68200.
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.

Q30134-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TGECYFFNGT
60 70 80 90 100
ERVRFLDRYF YNQEEYVRFD SDVGEYRAVT ELGRPSAEYW NSQKDFLEDR
110 120 130 140 150
RALVDTYCRH NYGVGESFTV QRRVHPKVTV YPSKTQPLQH HNLLVCSVSG
160 170 180 190 200
FYPGSIEVRW FRNGQEEKTG VVSTGLIHNG DWTFQTLVML ETVPRSGEVY
210 220 230 240 250
TCQVEHPSVT SPLTVEWSAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF
260
RNQKGHSGLQ PTGFLS
Length:266
Mass (Da):30,004
Last modified:August 29, 2003 - v2
Checksum:iD452D1C3A75CEA31
GO

Polymorphismi

The following alleles of DRB1-8 are known: DRB1*08:01 (Dw8.1), DRB1*08:02 (Dw8.2; DRB1L), DRB1*08:03 (Dw8.3); DRB1*08:04; DRB1*08:05, DRB1*08:06, DRB1*08:07, DRB1*08:08, DRB1*08:09, DRB1*08:10, DRB1*08:11, DRB1*08:12, DRB1*08:13, DRB1*08:14, DRB1*08:15, DRB1*08:16, DRB1*08:17, DRB1*08:18, DRB1*08:19, DRB1*08:20, DRB1*08:21, DRB1*08:22, DRB1*08:23, DRB1*08:24, DRB1*08:25, DRB1*08:26, DRB1*08:27, DRB1*08:28, DRB1*08:29, DRB1*08:30, DRB1*08:31, DRB1*08:32, DRB1*08:33, DRB1*08:34, DRB1*08:35 and DRB1*08:36. The sequence shown is that of DRB1*08:01.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti86 – 861S → D in allele DRB1*08:02 and allele DRB1*08:04; requires 2 nucleotide substitutions.
VAR_016683
Natural varianti96 – 961F → I in allele DRB1*08:03.
VAR_016684
Natural varianti115 – 1151G → V in allele DRB1*08:04.
VAR_016685
Natural varianti236 – 2361V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
VAR_056535
Natural varianti262 – 2621T → R.
Corresponds to variant rs9269744 [ dbSNP | Ensembl ].
VAR_056536

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M26038 mRNA. Translation: AAA59794.1.
S69987 Genomic DNA. Translation: AAD14052.1.
M17386 mRNA. No translation available.
M60216 Genomic DNA. Translation: AAA36298.1.
AJ249626 Genomic DNA. Translation: CAB56284.1.
AF330103 Genomic DNA. Translation: AAK08504.1.
AH010612 Genomic DNA. Translation: AAK31608.1.
AH010613 Genomic DNA. Translation: AAK31609.1.
AH010614 Genomic DNA. Translation: AAK31610.1.
M27511 Genomic DNA. Translation: AAA59817.1.
AF144105 Genomic DNA. Translation: AAD38374.1.
L10402 Genomic DNA. Translation: AAA51400.1.
M15074 mRNA. Translation: AAA59810.1.
PIRiA45856.
F60748.
I51875.
I54473.
I68778.
PH0160.
PT0161.
UniGeneiHs.534322.
Hs.696211.
Hs.736560.

Genome annotation databases

EnsembliENST00000328980; ENSP00000331343; ENSG00000206306.
ENST00000399450; ENSP00000382378; ENSG00000206240.

Polymorphism databases

DMDMi34395492.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M26038 mRNA. Translation: AAA59794.1 .
S69987 Genomic DNA. Translation: AAD14052.1 .
M17386 mRNA. No translation available.
M60216 Genomic DNA. Translation: AAA36298.1 .
AJ249626 Genomic DNA. Translation: CAB56284.1 .
AF330103 Genomic DNA. Translation: AAK08504.1 .
AH010612 Genomic DNA. Translation: AAK31608.1 .
AH010613 Genomic DNA. Translation: AAK31609.1 .
AH010614 Genomic DNA. Translation: AAK31610.1 .
M27511 Genomic DNA. Translation: AAA59817.1 .
AF144105 Genomic DNA. Translation: AAD38374.1 .
L10402 Genomic DNA. Translation: AAA51400.1 .
M15074 mRNA. Translation: AAA59810.1 .
PIRi A45856.
F60748.
I51875.
I54473.
I68778.
PH0160.
PT0161.
UniGenei Hs.534322.
Hs.696211.
Hs.736560.

3D structure databases

ProteinModelPortali Q30134.
SMRi Q30134. Positions 34-220.
ModBasei Search...
MobiDBi Search...

Polymorphism databases

DMDMi 34395492.

Proteomic databases

PaxDbi Q30134.
PRIDEi Q30134.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000328980 ; ENSP00000331343 ; ENSG00000206306 .
ENST00000399450 ; ENSP00000382378 ; ENSG00000206240 .

Organism-specific databases

GeneCardsi GC06M032546.
GC06Mj32477.
GC06Mn32480.
HGNCi HGNC:4948. HLA-DRB1.
MIMi 142857. gene.
neXtProti NX_Q30134.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG68200.
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 Q30134.
SOURCEi Search...

Gene expression databases

CleanExi HS_HLA-DRB1.
Genevestigatori Q30134.

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. "A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR beta ser 57- asp 57)."
    Jonsson A.K., Andersson L., Rask L.
    Immunogenetics 29:308-316(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*08:02).
  2. "The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequence."
    Emery P., Mach B., Reith W.
    Hum. Immunol. 38:137-147(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
  3. "Allelic variation in the DR subregion of the human major histocompatibility complex."
    Bell J.I., Denney D. Jr., Foster L., Belt T.K., Todd J.A., McDevitt H.O.
    Proc. Natl. Acad. Sci. U.S.A. 84:6234-6238(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-115 (ALLELE DRB1*08:01).
  4. "A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid arthritis."
    Van Kerckhove C., Melin-Aldana H., Elma M.S., Luyrink L., Donnelly P., Taylor J., Maksymowych W.P., Lovell D.J., Choi E., Glass D.N.
    Immunogenetics 32:304-308(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123.
  5. "A new DRB1*08 allele."
    Dormoy A., Froelich N., Weschler B., Tongio M.M.
    Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*08:01).
  6. "Human leukocyte antigen class II DRB1*0804 variant."
    Hurley C.K., Tang T., Li L.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*08:04).
    Tissue: Blood.
  7. "SBT of DRB1*0801, exons two and three."
    Greville W.D.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-208 (ALLELE DRB1*08:01).
  8. "Two distinct subtypes of the HLA-DRw12 haplotypes in the Japanese population detected by nucleotide sequence analysis and oligonucleotide genotyping."
    Abe A., Ito I., Ohkubo M., Kaneko T., Ito K., Kato H., Kashiwagi N., Obata F.
    Immunogenetics 30:422-426(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-115 (ALLELE DRB1*08:03).
  9. "Identification of a putative DR8 founder haplotype containing a novel DRB1*08 allele."
    Eberle M., Asu U., Taylor M., Hunter J.B., Fuller T.C., Maurer D.
    Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-120 (ALLELE DRB1*08:01).
  10. "Analysis of HLA class II haplotypes in the Cayapa Indians of Ecuador: a novel DRB1 allele reveals evidence for convergent evolution and balancing selection at position 86."
    Titus-Trachtenberg E.A., Rickards O., De Stefano G.F., Erlich H.A.
    Am. J. Hum. Genet. 55:160-167(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 47-122 (ALLELE DRB1*08:04).
    Tissue: Blood.
  11. "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.
  12. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 256-266.
  13. "Invariant chain structure and MHC class II function."
    Cresswell P.
    Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  14. "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.
  15. "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.
  16. "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.
  17. "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.
  18. "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.
  19. "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 namei2B18_HUMAN
AccessioniPrimary (citable) accession number: Q30134
Secondary accession number(s): O19718
, O19788, Q29968, Q30108, Q30115, Q9BCP0, Q9BCP1, Q9BCP2, Q9BD33, Q9TQ37, Q9UIM9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: August 29, 2003
Last modified: October 1, 2014
This is version 110 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