'''HLA class II histocompatibility antigen, DRB1 beta chain''' is a [[protein]] that in humans is encoded by the ''HLA-DRB1'' [[gene]].<ref name = "Entrez_Gene_3123">{{cite web | title = Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3123| accessdate = }}</ref> DRB1 encodes the most prevalent beta subunit of [[HLA-DR]]. Several alleles of DRB1 (shared epitope alleles)<ref name="pmid2446635">{{cite journal | vauthors = Gregersen PK, Silver J, Winchester RJ | title = The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 30 | issue = 11 | pages = 1205–13 | date = Nov 1987 | pmid = 2446635 | doi = 10.1002/art.1780301102 }}</ref> are associated with an increased incidence of [[rheumatoid arthritis]].
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== Function ==
{{PBB_Controls
The [[protein]] encoded by this gene belongs to the [[MHC class II|HLA class II]] beta chain [[Homology (biology)#Paralogy|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 cell]]s. Class II molecules are constitutively expressed in professional [[antigen presenting cell]]s (APC: B lymphocytes, dendritic cells, macrophages),<ref name = "Entrez_Gene_3123"/> and could be induced in non-professional [[antigen presenting cell|APCs]].
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== Gene structure and polymorphisms ==
{{GNF_Protein_box
The beta chain is approximately 26-28 kDa. It is encoded by 6 [[exon]]s, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular [[protein domain|domains]], exon 4 encodes the [[transmembrane protein|transmembrane]] domain and exon 5 encodes the [[cytoplasm]]ic tail. Within the DR molecule the beta chain contains all the [[polymorphism (biology)|polymorphism]]s specifying the peptide binding specificities. Hundreds of DRB1 [[allele]]s have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation.<ref name = "Entrez_Gene_3123"/>
| image = PBB_Protein_HLA-DRB1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1aqd.
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| DateOfBotUpdate = 07:27, 9 October 2007 (UTC)
| Function = {{GNF_GO|id=GO:0032395 |text = MHC class II receptor activity}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0042613 |text = MHC class II protein complex}}
| Process = {{GNF_GO|id=GO:0002504 |text = antigen processing and presentation of peptide or polysaccharide antigen via MHC class II}} {{GNF_GO|id=GO:0006955 |text = immune response}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 3123
| Hs_Ensembl = ENSG00000196126
| Hs_RefseqProtein = NP_002115
| Hs_RefseqmRNA = NM_002124
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 6
| Hs_GenLoc_start = 32654524
| Hs_GenLoc_end = 32665603
| Hs_Uniprot = P01911
| Mm_EntrezGene = 14969
| Mm_Ensembl = ENSMUSG00000060586
| Mm_RefseqmRNA = NM_010382
| Mm_RefseqProtein = NP_034512
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 17
| Mm_GenLoc_start = 33913591
| Mm_GenLoc_end = 33923315
| Mm_Uniprot = O19450
}}
}}
'''Major histocompatibility complex, class II, DR beta 1''', also known as '''HLA-DRB1''', is a human [[gene]].
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== Gene expression ==
{{PBB_Summary
DRB1 is expressed at a level five times higher than its paralogues [[HLA-DRB3|DRB3]], [[HLA-DRB4|DRB4]] and [[HLA-DRB5|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 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.<ref name = "Entrez_Gene_3123"/>
| section_title =
| summary_text = HLA-DRB1 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. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). 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. 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 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.<ref>{{cite web | title = Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3123| accessdate = }}</ref>
}}
==References==
== See also ==
{{reflist|2}}
* [[HLA-DR]]
==Further reading==
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Turesson C, Matteson EL | title = Genetics of rheumatoid arthritis | journal = Mayo Clinic Proceedings | volume = 81 | issue = 1 | pages = 94–101 | date = Jan 2006 | pmid = 16438485 | doi = 10.4065/81.1.94 }}
| citations =
* {{cite journal | vauthors = Ahmad T, Marshall SE, Jewell D | title = Genetics of inflammatory bowel disease: the role of the HLA complex | journal = World Journal of Gastroenterology | volume = 12 | issue = 23 | pages = 3628–35 | date = Jun 2006 | pmid = 16773677 | doi = 10.3748/wjg.v12.i23.3628}}
*{{cite journal | author=Turesson C, Matteson EL |title=Genetics of rheumatoid arthritis. |journal=Mayo Clin. Proc. |volume=81 |issue= 1 |pages= 94-101 |year= 2006 |pmid= 16438485 |doi= }}
* {{cite journal | vauthors = Schmidt H, Williamson D, Ashley-Koch A | title = HLA-DR15 haplotype and multiple sclerosis: a HuGE review | journal = American Journal of Epidemiology | volume = 165 | issue = 10 | pages = 1097–109 | date = May 2007 | pmid = 17329717 | doi = 10.1093/aje/kwk118 }}
*{{cite journal | author=Ahmad T, Marshall SE, Jewell D |title=Genetics of inflammatory bowel disease: the role of the HLA complex. |journal=World J. Gastroenterol. |volume=12 |issue= 23 |pages= 3628-35 |year= 2006 |pmid= 16773677 |doi= }}
*{{cite journal | author=Schmidt H, Williamson D, Ashley-Koch A |title=HLA-DR15 haplotype and multiple sclerosis: a HuGE review. |journal=Am. J. Epidemiol. |volume=165 |issue= 10 |pages= 1097-109 |year= 2007 |pmid= 17329717 |doi= 10.1093/aje/kwk118 }}
HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1gene.[1] DRB1 encodes the most prevalent beta subunit of HLA-DR. Several alleles of DRB1 (shared epitope alleles)[2] are associated with an increased incidence of rheumatoid arthritis.
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),[1] 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.[1]
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 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.[1]
↑Gregersen PK, Silver J, Winchester RJ (Nov 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. PMID2446635.
Further reading
Turesson C, Matteson EL (Jan 2006). "Genetics of rheumatoid arthritis". Mayo Clinic Proceedings. 81 (1): 94–101. doi:10.4065/81.1.94. PMID16438485.
Ahmad T, Marshall SE, Jewell D (Jun 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. PMID16773677.
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. PMID17329717.
1pyw: Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
2fse: Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele, HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type II collagen
2ipk: Crystal Structure of the MHC Class II Molecule HLA-DR1 in Complex with the Fluorogenic Peptide, AcPKXVKQNTLKLAT (X=3-[5-(dimethylamino)-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl]-L-alanine) and the Superantigen, SEC3 Variant 3B2
![2ipk: Crystal Structure of the MHC Class II Molecule HLA-DR1 in Complex with the Fluorogenic Peptide, AcPKXVKQNTLKLAT (X=3-[5-(dimethylamino)-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl]-L-alanine) and the Superantigen, SEC3 Variant 3B2](/index.php?title=Special:Upload&wpDestFile=PDB_2ipk_EBI.jpg){kind=link}
