Q30167 (2B1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class II histocompatibility antigen, DRB1-10 beta chain

Alternative name(s):
DRw10
MHC class II antigen DRB1*10

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.9
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.9
Polymorphism	The following alleles of DRB1-10 are known: DRB1*10:01; DRB1*10:02 and DRB1*10:03. The sequence shown is that of DRB1*10:01.
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.9. Source: UniProtKB lysosomal membrane Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29
	Chain	30 – 266	237	HLA class II histocompatibility antigen, DRB1-10 beta chain		PRO_0000018954
Regions
	Topological domain	30 – 227	198	Extracellular Potential
	Transmembrane	228 – 250	23	Helical; Potential
	Topological domain	251 – 266	16	Cytoplasmic Potential
	Domain	126 – 216	91	Ig-like C1-type
	Region	30 – 124	95	Beta-1
	Region	125 – 227	103	Beta-2
Amino acid modifications
	Glycosylation	48	1	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	236	1	V → M. Corresponds to variant rs2230816 [ dbSNP | Ensembl ].		VAR_056540
	Natural variant	262	1	T → R. Corresponds to variant rs9269744 [ dbSNP | Ensembl ].		VAR_056541
Experimental info
	Sequence conflict	180	1	G → E in AAA59832. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q30167 [UniParc]. Last modified March 23, 2010. Version 2. Checksum: 45AB410F8AC21750	FASTA	266	30,002
	10 20 30 40 50 60 MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEEV KFECHFFNGT ERVRLLERRV 70 80 90 100 110 120 HNQEEYARYD SDVGEYRAVT ELGRPDAEYW NSQKDLLERR RAAVDTYCRH NYGVGESFTV 130 140 150 160 170 180 QRRVQPKVTV YPSKTQPLQH HNLLVCSVNG FYPGSIEVRW FRNGQEEKTG VVSTGLIQNG 190 200 210 220 230 240 DWTFQTLVML ETVPQSGEVY TCQVEHPSVM SPLTVEWRAR SESAQSKMLS GVGGFVLGLL 250 260 FLGAGLFIYF RNQKGHSGLP PTGFLS

References

[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: 6589154] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*10:01).
[2]	"Nucleotide sequence of a DRw10 beta chain cDNA clone. Identity of the third D region with that of the DRw53 allele of the beta 2 locus and as the probable site encoding a polymorphic MHC class II epitope." Merryman P., Gregersen P.K., Lee S., Silver J., Nunez-Roldan A., Crapper R., Winchester R. J. Immunol. 140:2447-2452(1988) [PubMed: 2450924] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*10:01).
[3]	"Molecular analysis of human class II transplantation antigens and their genes." Larhammar D., Andersson G., Andersson M., Bill P., Boehme J., Claesson L., Denaro M., Emmoth E., Gustafsson K., Hammarling U., Heldin E., Hyldig-Nielsen J.-J., Lind P., Schenning L., Servenius B., Widmark E., Rask L., Peterson P.A. Hum. Immunol. 8:95-103(1983) [PubMed: 6415003] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-266 (ALLELE DRB1*10:01).
[4]	"Sequence of an HLA-DRB gene." Woelpl A. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*10:01).
[5]	"Invariant chain structure and MHC class II function." Cresswell P. Cell 84:505-507(1996) [PubMed: 8598037] [Abstract] Cited for: REVIEW.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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	X00700 mRNA. Translation: CAA25296.1. M20138 mRNA. Translation: AAA59832.1. AF225565 Genomic DNA. Translation: AAF65542.1.
IPI	IPI00473139.
PIR	HLHU4D. A27614.
UniGene	Hs.534322. Hs.696211.
3D structure databases
ProteinModelPortal	Q30167.
SMR	Q30167. Positions 30-219.
ModBase	Search...
Protein-protein interaction databases
STRING	Q30167.
Polymorphism databases
DMDM	292494999.
Proteomic databases
PRIDE	Q30167.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000419393; ENSP00000403458; ENSG00000228080. ENST00000450362; ENSP00000410118; ENSG00000228080.
Organism-specific databases
GeneCards	GC06M032546.
HGNC	HGNC:4948. HLA-DRB1.
MIM	142857. gene.
neXtProt	NX_Q30167.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG012730.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q30167.
CleanEx	HS_HLA-DRB1.
Genevestigator	Q30167.
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

2B1A_HUMAN

Accession

Primary (citable) accession number: Q30167
Secondary accession number(s): P01914, Q9MYF5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	March 23, 2010
Last modified:	January 25, 2012
This is version 85 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.