HLA-DRB1

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene.[3] DRB1 encodes the most prevalent beta subunit of HLA-DR. DRB1 alleles, especially those encoding amino acid sequence changes at positions 11 and 13, are associated risk of rheumatoid arthritis.[4][5]

HLA-DRB1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1A6A, 1BX2, 1YMM, 2WBJ,%%s1AQD, 1DLH, 1FYT, 1HXY, 1JWM, 1JWS, 1JWU, 1KG0, 1KLG, 1KLU, 1LO5, 1PYW, 1R5I, 1SEB, 1SJH, 1T5W, 1T5X, 2FSE, 2G9H, 2IAM, 2IAN, 2ICW, 2IPK, 2OJE, 2XN9, 3L6F, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 3S4S, 3S5L, 4AEN, 4AH2, 4C56, 4E41, 4FQX, 4GBX, 4I5B, 4OV5, 4X5W, 4X5X,%%s1D5M, 1D5X, 1D5Z, 1D6E, 1J8H, 2SEB, 3O6F, 3T0E, 4IS6, 4MCY, 4MCZ, 4MD0, 4MD4, 4MD5, 4MDI, 4MDJ, 4Y19, 4Y1A
Identifiers
Aliases	HLA-DRB1, DRB1, DRw10, HLA-DR1B, HLA-DRB, SS1, major histocompatibility complex, class II, DR beta 1
External IDs	OMIM: 142857 HomoloGene: 136635 GeneCards: HLA-DRB1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.32 Start 32,578,769 bp[1] End 32,589,848 bp[1]
Gene ontology Molecular function • peptide antigen binding • MHC class II receptor activity • GO:0001948 protein binding • MHC class II protein complex binding Cellular component • integral component of membrane • endocytic vesicle membrane • clathrin-coated endocytic vesicle membrane • endosome • Golgi apparatus • trans-Golgi network membrane • endoplasmic reticulum membrane • membrane • late endosome membrane • Golgi membrane • cell membrane • transport vesicle membrane • MHC class II protein complex • lysosomal membrane • endoplasmic reticulum • ER to Golgi transport vesicle membrane • lysosome • integral component of lumenal side of endoplasmic reticulum membrane • endosome membrane • external side of plasma membrane • cell surface • extracellular exosome Biological process • antigen processing and presentation • antigen processing and presentation of exogenous peptide antigen via MHC class II • immune system process • interferon-gamma-mediated signaling pathway • immunoglobulin production involved in immunoglobulin mediated immune response • antigen processing and presentation of peptide or polysaccharide antigen via MHC class II • humoral immune response mediated by circulating immunoglobulin • immune response • peptide antigen assembly with MHC class II protein complex • T cell receptor signaling pathway • adaptive immune response • negative regulation of interferon-gamma production • inflammatory response to antigenic stimulus • protein tetramerization • regulation of interleukin-4 production • negative regulation of T cell proliferation • T-helper 1 type immune response • positive regulation of insulin secretion involved in cellular response to glucose stimulus • T cell costimulation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3123	n/a
Ensembl	ENSG00000236884 ENSG00000206240 ENSG00000229074 ENSG00000196126 ENSG00000206306 ENSG00000228080	n/a
UniProt	P01911	n/a
RefSeq (mRNA)	NM_001243965 NM_002124 NM_001359193 NM_001359194	n/a
RefSeq (protein)	NP_001230894 NP_002115 NP_001346122 NP_001346123 NP_002115.2	n/a
Location (UCSC)	Chr 6: 32.58 – 32.59 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

Function

The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins to T helper cells. Class II molecules are constitutively expressed in professional antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages),[3] and could be induced in non-professional APCs.

Gene structure and polymorphisms

The beta chain is approximately 26-28 kDa. It is encoded by 6 exons, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation.[3]

Gene expression

DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 5 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.[3]

Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease.[6]

See also

• HLA-DR

References

1. ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 GRCh38: Ensembl release 89: ENSG00000236884, ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1".
4. Gregersen PK, Silver J, Winchester RJ (November 1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis and Rheumatism. 30 (11): 1205–13. doi:10.1002/art.1780301102. PMID 2446635.
5. Raychaudhuri, S; Sandor, C; Stahl, EA; Freudenberg, J; Lee, HS; Jia, X; Alfredsson, L; Padyukov, L; Klareskog, L; Worthington, J; Siminovitch, KA; Bae, SC; Plenge, RM; Gregersen, PK; de Bakker, PI (29 January 2012). "Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis". Nature Genetics. 44 (3): 291–6. doi:10.1038/ng.1076. PMC 3288335. PMID 22286218.
6. Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, Giordana C, Heidbreder A, Kotschet K, Lewerenz J, Macher S, Martí MJ, Montojo T, Pérez-Pérez J, Puertas I, Seitz C, Simabukuro M, Téllez N, Wandinger KP, Iranzo A, Ercilla G, Sabater L, Santamaría J, Dalmau J (May 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC 5409845. PMID 28381508.

Further reading

• Turesson C, Matteson EL (January 2006). "Genetics of rheumatoid arthritis". Mayo Clinic Proceedings. 81 (1): 94–101. doi:10.4065/81.1.94. PMID 16438485.
• Ahmad T, Marshall SE, Jewell D (June 2006). "Genetics of inflammatory bowel disease: the role of the HLA complex". World Journal of Gastroenterology. 12 (23): 3628–35. doi:10.3748/wjg.v12.i23.3628. PMC 4087453. PMID 16773677.
• Schmidt H, Williamson D, Ashley-Koch A (May 2007). "HLA-DR15 haplotype and multiple sclerosis: a HuGE review". American Journal of Epidemiology. 165 (10): 1097–109. doi:10.1093/aje/kwk118. PMID 17329717.