HLA-DRB1

HLA-DRB1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	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
Identifikatori
Aliasi	HLA-DRB1
Vanjski ID-jevi	OMIM: 142857 MGI: 95901 HomoloGene: 136635 GeneCards: HLA-DRB1
Lokacija gena (čovjek)
Hrom.	Hromosom 6 (čovjek)
Kraj	32,589,848 bp
Lokacija gena (miš)
Hrom.	Hromosom 17 (miš)
Kraj	34,535,648 bp
Ontologija gena
Molekularna funkcija	• peptide antigen binding; • MHC class II receptor activity; • GO:0001948, GO:0016582 vezivanje za proteine; • MHC class II protein complex binding;
Ćelijska komponenta	• integral component of membrane; • endocytic vesicle membrane; • clathrin-coated endocytic vesicle membrane; • endozom; • Golđijev aparat; • trans-Golgi network membrane; • endoplasmic reticulum membrane; • membrana; • late endosome membrane; • Golđijeva membrana; • ćelijska membrana; • transport vesicle membrane; • MHC class II protein complex; • lysosomal membrane; • Endoplazmatski retikulum; • ER to Golgi transport vesicle membrane; • Lizozom; • integral component of lumenal side of endoplasmic reticulum membrane; • endosome membrane; • external side of plasma membrane; • cell surface; • Egzosom;
Biološki proces	• 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; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor; • 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;
	Izvori:Amigo / QuickGO
Ortolozi
	3123
	14969
ENSG00000236884; ENSG00000206240; ENSG00000229074; ENSG00000196126; ENSG00000206306;
	ENSG00000228080
	ENSMUSG00000060586
	P01911
P04231; P04230; P18468; P18469; O78196;
	n/a
	NM_001243965; NM_002124; NM_001359193; NM_001359194
	NM_010382
	NP_001230894; NP_002115; NP_001346122; NP_001346123; NP_002115.2
	NP_034512
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

DRB1 beta lanac HLA klase II antigena histokompatibilnosti jest protein koji je kod ljudi kodiran genom HLA-DRB1 sa hromosoma 6.^[5] DRB1 kodira najzastupljeniju beta podjedinicu HLA-DR-a. Aleli DRB1, posebno oni koji kodiraju promjene sekvence aminokiselina na pozicijama 11 i 13, povezani su sa rizikom od reumatoidnog artritisa.^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 266 aminokiselina, a molekulska težina 29.966 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MVCLKLPGGS	CMTALTVTLM	VLSSPLALSG	DTRPRFLWQP	KRECHFFNGT
ERVRFLDRYF	YNQEESVRFD	SDVGEFRAVT	ELGRPDAEYW	NSQKDILEQA
RAAVDTYCRH	NYGVVESFTV	QRRVQPKVTV	YPSKTQPLQH	HNLLVCSVSG
FYPGSIEVRW	FLNGQEEKAG	MVSTGLIQNG	DWTFQTLVML	ETVPRSGEVY
TCQVEHPSVT	SPLTVEWRAR	SESAQSKMLS	GVGGFVLGLL	FLGAGLFIYF
RNQKGHSGLQ	PTGFLS

Funkcija

protein kodiran ovim genom pripada HLA klasi II beta lanca paraloga. Molekula klase II je heterodimer koji se sastoji od alfa (DRA) i beta lanca (DRB), oba usidrena u membrani. Ima centralnu ulogu u imunskom sistemu prezentirajući peptide izvedene iz vanćelijskih proteina u T-pomoćnim ćelijama. Molekule klase II eksprimirane su konstitutivno u profesionalnim ćelijama koje prezentiraju antigen (APC: B-limfociti, dendritske ćelije, makrofagi),^[5] i mogu se inducirati u neprofesionalnim APC-ima.

Postoje dokazi da je povezan sa smanjenom ozbiljnošću bolesti COVID-19 i da bi mogao biti izazvan kod neprofesionalnih APC.^[9]

Struktura gena i polimorfizmi

Beta lanac je velik otprilike 26-28 kDa. Kodira ga šest egzona; egzon 1 kodira vodeći peptid, egzoni 2 i 3 kodiraju dva vančelijskaa domena, egzon 4 kodira transmembranski domen i egzon 5 kodira citoplazmatski rep. Unutar DR molekula, beta lanac sadrži sve polimorfizme koji određuju specifičnosti vezivanja peptida. Opisane su stotine DRB1 alela i tipizacija za ove polimorfizme se rutinski radi za transplantaciju koštane srži i bubrega.^[5]

Ekspresija gena

DRB1 je eksprimiran na nivou pet puta većem od njegovih paraloga DRB3, DRB4 i DRB5. DRB1 je prisutan kod svih osoba. Alelne varijante DRB1 su povezane ni sa jednim ili sa jednim od gena DRB3, DRB4 i DRB5. Postoji pet povezanih pseudogena: DRB2, DRB6, DRB7, DRB8 i DRB9.^[5]

Prevalencija alela HLA-DRB1*10:01 je značajno povećana kod ljudi sa bolešću anti-IgLON5.^[10]

Također pogledajte

HLA-DR

Reference

^ ^a ^b ^c ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 GRCh38: Ensembl release 89: ENSG00000236884, ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000060586 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c ^d "Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1".
^ Gregersen PK, Silver J, Winchester RJ (novembar 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.
^ 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. 1. 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.
^ "UniProt, P01911" (jezik: engleski). Pristupljeno 6. 9. 2017.
^ Langton, David J.; Bourke, Stephen C.; Lie, Benedicte A.; Reiff, Gabrielle; Natu, Shonali; Darlay, Rebecca; Burn, John; Echevarria, Carlos (4. 5. 2021). "The influence of HLA genotype on the severity of COVID‐19 infection". HLA (jezik: engleski): tan.14284. doi:10.1111/tan.14284. ISSN 2059-2302. PMC 8251294 Provjerite vrijednost parametra |pmc= (pomoć).
^ 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 (maj 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC 5409845. PMID 28381508.

Dopunska literatura

Turesson C, Matteson EL (januar 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 (juni 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 (maj 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.

Vanjski linkovi

[refGRCh38Ensembl-1] ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 GRCh38: Ensembl release 89: ENSG00000236884, ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000060586 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Entrez_Gene_3123-5] "Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1".

[pmid2446635-6] Gregersen PK, Silver J, Winchester RJ (novembar 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.

[7] 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. 1. 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.

[UniProt-8] "UniProt, P01911" (jezik: engleski). Pristupljeno 6. 9. 2017.

[9] Langton, David J.; Bourke, Stephen C.; Lie, Benedicte A.; Reiff, Gabrielle; Natu, Shonali; Darlay, Rebecca; Burn, John; Echevarria, Carlos (4. 5. 2021). "The influence of HLA genotype on the severity of COVID‐19 infection". HLA (jezik: engleski): tan.14284. doi:10.1111/tan.14284. ISSN 2059-2302. PMC 8251294 Provjerite vrijednost parametra |pmc= (pomoć).

[10] 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 (maj 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC 5409845. PMID 28381508.

[5]

[6]

[7]

[1]

[2]

[3]

[4]

[8]

[9]

[10]