HLA-DRB1

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. 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.

HLA-DRB1
Available structures PDB Ortholog 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; MGI: 95901; HomoloGene: 136635; GeneCards: HLA-DRB1; OMA:HLA-DRB1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6p21.32 Start 32,577,902 bp End 32,589,848 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 B1|17 17.98 cM Start 34,524,841 bp End 34,535,648 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in appendix granulocyte right lung lymph node spleen upper lobe of left lung monocyte gallbladder duodenum right coronary artery Top expressed in mesenteric lymph nodes spleen thymus submandibular gland carotid body right lung lip white adipose tissue right lung lobe tibiofemoral joint More reference expression data BioGPS n/a
Gene ontology Molecular function peptide antigen binding MHC class II receptor activity 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 plasma 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 14969 Ensembl ENSG00000236884 ENSG00000206240 ENSG00000229074 ENSG00000196126 ENSG00000206306 ENSG00000228080 ENSMUSG00000060586 UniProt P01911 P04231 P04230 P18468 P18469 O78196 n/a RefSeq (mRNA) NM_001243965 NM_002124 NM_001359193 NM_001359194 NM_010382 RefSeq (protein) NP_001230894 NP_002115 NP_001346122 NP_001346123 NP_002115.2 NP_034512 Location (UCSC) Chr 6: 32.58 – 32.59 Mb Chr 17: 34.52 – 34.54 Mb PubMed search
Wikidata
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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), and could be induced in non-professional APCs.

There is evidence it is associated with reduced severity of COVID-19 disease.

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. To date, more than 3,700 HLA-DRB1 alleles have been described and made publicaly available in the IPD-IMGT/HLA Database. HLA typing for these polymorphisms is routinely done for bone marrow and kidney transplantation.

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.

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

See also

• HLA-DR

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.