HLA class II histocompatibility antigen, DRB1-8 beta chain precursor

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Q30134 (2B18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:

HLA-DRB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	266 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 accomodates 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 an 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 miroenvironment 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 an 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 apparatus › trans-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.17
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.17
Polymorphism	The following alleles of DRB1-8 are known: DRB108:01 (Dw8.1), DRB108:02 (Dw8.2; DRB1L), DRB108:03 (Dw8.3); DRB108:04; DRB108:05, DRB108:06, DRB108:07, DRB108:08, DRB108:09, DRB108:10, DRB108:11, DRB108:12, DRB108:13, DRB108:14, DRB108:15, DRB108:16, DRB108:17, DRB108:18, DRB108:19, DRB108:20, DRB108:21, DRB108:22, DRB108:23, DRB108:24, DRB108:25, DRB108:26, DRB108:27, DRB108:28, DRB108:29, DRB108:30, DRB108:31, DRB108:32, DRB108:33, DRB108:34, DRB108:35 and DRB108:36. The sequence shown is that of DRB1*08:01.
Sequence similarities	Belongs to the MHC class II family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome MHC II Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome antigen processing and presentation of peptide or polysaccharide antigen via MHC class II Inferred from electronic annotation. Source: UniProtKB-KW interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell MHC class II protein complex Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosome membrane Inferred from direct assay Ref.17. Source: UniProtKB lysosomal membrane Inferred from direct assay Ref.17. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

Chain

30 – 266

237

HLA class II histocompatibility antigen, DRB1-8 beta chain

PRO_0000018952

Regions

Topological domain

30 – 227

198

Extracellular Potential

Transmembrane

228 – 250

Helical; Potential

Topological domain

251 – 266

Cytoplasmic Potential

Domain

126 – 214

Ig-like C1-type

Region

30 – 124

Beta-1

Region

125 – 227

103

Beta-2

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

44 ↔ 108

By similarity

Disulfide bond

146 ↔ 202

By similarity

Cross-link

254

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Natural variant

S → D in allele DRB1*08:02 and allele DRB1*08:04; requires 2 nucleotide substitutions.

VAR_016683

Natural variant

F → I in allele DRB1*08:03.

VAR_016684

Natural variant

115

G → V in allele DRB1*08:04.

VAR_016685

Natural variant

236

V → M.
Corresponds to variant rs2230816 [ dbSNP | Ensembl ].

VAR_056535

Natural variant

262

T → R.
Corresponds to variant rs9269744 [ dbSNP | Ensembl ].

VAR_056536

Sequences

Sequence

Length

Mass (Da)

Tools

Q30134 [UniParc].

Last modified August 29, 2003. Version 2.
Checksum: D452D1C3A75CEA31
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FASTA

266

30,004

        10         20         30         40         50         60 
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TGECYFFNGT ERVRFLDRYF 

        70         80         90        100        110        120 
YNQEEYVRFD SDVGEYRAVT ELGRPSAEYW NSQKDFLEDR RALVDTYCRH NYGVGESFTV 

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

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

       250        260 
FLGAGLFIYF RNQKGHSGLQ PTGFLS

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References

[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: 2497068] [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: 8106268] [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: 3476943] [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: 1979063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123.
[5]	*"A new DRB108 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 DRB10804 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 DRB10801, 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: 2592019] [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 DRB108 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: 8023844] [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: 2471740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-217.
[12]	"Molecular diversity of HLA-DR4 haplotypes." Gregersen P.K., Shen M., Song Q.-L., Merryman P., Degar S., Seki T., Maccari J., Goldberg D., Murphy H., Schwenzer J., Wang C.Y., Winchester R.J., Nepom G.T., Silver J. Proc. Natl. Acad. Sci. U.S.A. 83:2642-2646(1986) [PubMed: 3458223] [Abstract] 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: 8598037] [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: 11684289] [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: 17241953] [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: 18046453] [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: 18305173] [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: 19092054] [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: 19533806] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AY028515, AY028514 Genomic DNA. Translation: AAK31608.1. AY028517, AY028516 Genomic DNA. Translation: AAK31609.1. AY028519, AY028518 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.
IPI	IPI00005180.
PIR	A45856. F60748. I51875. I54473. I68778. PH0160. PT0161.
UniGene	Hs.534322. Hs.696211.
3D structure databases
ProteinModelPortal	Q30134.
SMR	Q30134. Positions 34-220.
ModBase	Search...
Protein-protein interaction databases
STRING	Q30134.
Polymorphism databases
DMDM	34395492.
Proteomic databases
PRIDE	Q30134.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328980; ENSP00000331343; ENSG00000206306. ENST00000399450; ENSP00000382378; ENSG00000206240.
Organism-specific databases
GeneCards	GC06M032546. GC06Mn32480.
HGNC	HGNC:4948. HLA-DRB1.
MIM	142857. gene.
neXtProt	NX_Q30134.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG012730.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
CleanEx	HS_HLA-DRB1.
Genevestigator	Q30134.
Family and domain databases
InterPro	IPR007110. Ig-like. 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]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit. G3DSA:3.10.320.10. MHC_II_alpha_N. 1 hit.
Pfam	PF07654. C1-set. 1 hit. PF00969. MHC_II_beta. 1 hit. [Graphical view]
ProDom	PD000328. MHC_II_b_N. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00407. IGc1. 1 hit. SM00921. MHC_II_beta. 1 hit. [Graphical view]
SUPFAM	SSF54452. MHC_I/II-like_Ag-recog. 1 hit.
PROSITE	PS50835. IG_LIKE. 1 hit. PS00290. IG_MHC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

2B18_HUMAN

Accession

Primary (citable) accession number: Q30134
Secondary accession number(s): O19718

Q9UIM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	August 29, 2003
Last modified:	January 25, 2012
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents