ARID1A

S Wikipedije, slobodne enciklopedije
ARID1A
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1RYU

Identifikatori
AliasiARID1A
Vanjski ID-jeviOMIM: 603024 MGI: 1935147 HomoloGene: 21216 GeneCards: ARID1A
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za ARID1A
Genomska lokacija za ARID1A
Bend1p36.11Početak26,693,236 bp[1]
Kraj26,782,104 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za ARID1A
Genomska lokacija za ARID1A
Bend4|4 D2.3Početak133,679,008 bp[2]
Kraj133,756,769 bp[2]
Obrazac RNK ekspresije




Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija DNA binding
GO:0001105 transcription coactivator activity
GO:0001948, GO:0016582 protein binding
nuclear receptor binding
nucleosome binding
GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
Ćelijska komponenta nBAF complex
SWI/SNF complex
Nukleoplazma
npBAF complex
Jedro
SWI/SNF superfamily-type complex
brahma complex
Biološki proces androgen receptor signaling pathway
chromatin remodeling
GO:0009373 regulation of transcription, DNA-templated
GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II
cardiac muscle cell differentiation
optic cup formation involved in camera-type eye development
placenta blood vessel development
GO:1901227 negative regulation of transcription by RNA polymerase II
toxin transport
GO:0031497, GO:0006336, GO:0034724, GO:0001301, GO:0007580, GO:0034652, GO:0010847 chromatin organization
transcription, DNA-templated
nervous system development
cardiac chamber development
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
neural tube closure
nucleosome disassembly
forebrain development
intracellular estrogen receptor signaling pathway
glucocorticoid receptor signaling pathway
formation of primary germ layer
Gastrulacija
embryo implantation
stem cell population maintenance
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_139135
NM_006015
NM_018450

NM_001080819
NM_001363070

RefSeq (bjelančevina)

NP_006006
NP_624361

NP_001074288
NP_001349999
NP_001388200
NP_001388202
NP_001388204

NP_001388205

Lokacija (UCSC)Chr 1: 26.69 – 26.78 MbChr 4: 133.68 – 133.76 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

AT-bogati interaktivni protein 1A sa domenom jest protein koji je kod ljudi kodiran genom ARID1A sa hromosoma 1.[5][6][7]

Amiokiselininska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 2.285 aminokiselina, a molekulska težina 242.045 Da.[8]

1020304050
MAAQVAPAAASSLGNPPPPPPSELKKAEQQQREEAGGEAAAAAAAERGEM
KAAAGQESEGPAVGPPQPLGKELQDGAESNGGGGGGGAGSGGGPGAEPDL
KNSNGNAGPRPALNNNLTEPPGGGGGGSSDGVGAPPHSAAAALPPPAYGF
GQPYGRSPSAVAAAAAAVFHQQHGGQQSPGLAALQSGGGGGLEPYAGPQQ
NSHDHGFPNHQYNSYYPNRSAYPPPAPAYALSSPRGGTPGSGAAAAAGSK
PPPSSSASASSSSSSFAQQRFGAMGGGGPSAAGGGTPQPTATPTLNQLLT
SPSSARGYQGYPGGDYSGGPQDGGAGKGPADMASQCWGAAAAAAAAAAAS
GGAQQRSHHAPMSPGSSGGGGQPLARTPQPSSPMDQMGKMRPQPYGGTNP
YSQQQGPPSGPQQGHGYPGQPYGSQTPQRYPMTMQGRAQSAMGGLSYTQQ
IPPYGQQGPSGYGQQGQTPYYNQQSPHPQQQQPPYSQQPPSQTPHAQPSY
QQQPQSQPPQLQSSQPPYSQQPSQPPHQQSPAPYPSQQSTTQQHPQSQPP
YSQPQAQSPYQQQQPQQPAPSTLSQQAAYPQPQSQQSQQTAYSQQRFPPP
QELSQDSFGSQASSAPSMTSSKGGQEDMNLSLQSRPSSLPDLSGSIDDLP
MGTEGALSPGVSTSGISSSQGEQSNPAQSPFSPHTSPHLPGIRGPSPSPV
GSPASVAQSRSGPLSPAAVPGNQMPPRPPSGQSDSIMHPSMNQSSIAQDR
GYMQRNPQMPQYSSPQPGSALSPRQPSGGQIHTGMGSYQQNSMGSYGPQG
GQYGPQGGYPRQPNYNALPNANYPSAGMAGGINPMGAGGQMHGQPGIPPY
GTLPPGRMSHASMGNRPYGPNMANMPPQVGSGMCPPPGGMNRKTQETAVA
MHVAANSIQNRPPGYPNMNQGGMMGTGPPYGQGINSMAGMINPQGPPYSM
GGTMANNSAGMAASPEMMGLGDVKLTPATKMNNKADGTPKTESKSKKSSS
STTTNEKITKLYELGGEPERKMWVDRYLAFTEEKAMGMTNLPAVGRKPLD
LYRLYVSVKEIGGLTQVNKNKKWRELATNLNVGTSSSAASSLKKQYIQCL
YAFECKIERGEDPPPDIFAAADSKKSQPKIQPPSPAGSGSMQGPQTPQST
SSSMAEGGDLKPPTPASTPHSQIPPLPGMSRSNSVGIQDAFNDGSDSTFQ
KRNSMTPNPGYQPSMNTSDMMGRMSYEPNKDPYGSMRKAPGSDPFMSSGQ
GPNGGMGDPYSRAAGPGLGNVAMGPRQHYPYGGPYDRVRTEPGIGPEGNM
STGAPQPNLMPSNPDSGMYSPSRYPPQQQQQQQQRHDSYGNQFSTQGTPS
GSPFPSQQTTMYQQQQQNYKRPMDGTYGPPAKRHEGEMYSVPYSTGQGQP
QQQQLPPAQPQPASQQQAAQPSPQQDVYNQYGNAYPATATAATERRPAGG
PQNQFPFQFGRDRVSAPPGTNAQQNMPPQMMGGPIQASAEVAQQGTMWQG
RNDMTYNYANRQSTGSAPQGPAYHGVNRTDEMLHTDQRANHEGSWPSHGT
RQPPYGPSAPVPPMTRPPPSNYQPPPSMQNHIPQVSSPAPLPRPMENRTS
PSKSPFLHSGMKMQKAGPPVPASHIAPAPVQPPMIRRDITFPPGSVEATQ
PVLKQRRRLTMKDIGTPEAWRVMMSLKSGLLAESTWALDTINILLYDDNS
IMTFNLSQLPGLLELLVEYFRRCLIEIFGILKEYEVGDPGQRTLLDPGRF
SKVSSPAPMEGGEEEEELLGPKLEEEEEEEVVENDEEIAFSGKDKPASEN
SEEKLISKFDKLPVKIVQKNDPFVVDCSDKLGRVQEFDSGLLHWRIGGGD
TTEHIQTHFESKTELLPSRPHAPCPPAPRKHVTTAEGTPGTTDQEGPPPD
GPPEKRITATMDDMLSTRSSTLTEDGAKSSEAIKESSKFPFGISPAQSHR
NIKILEDEPHSKDETPLCTLLDWQDSLAKRCVCVSNTIRSLSFVPGNDFE
MSKHPGLLLILGKLILLHHKHPERKQAPLTYEKEEEQDQGVSCNKVEWWW
DCLEMLRENTLVTLANISGQLDLSPYPESICLPVLDGLLHWAVCPSAEAQ
DPFSTLGPNAVLSPQRLVLETLSKLSIQDNNVDLILATPPFSRLEKLYST
MVRFLSDRKNPVCREMAVVLLANLAQGDSLAARAIAVQKGSIGNLLGFLE
DSLAATQFQQSQASLLHMQNPPFEPTSVDMMRRAARALLALAKVDENHSE
FTLYESRLLDISVSPLMNSLVSQVICDVLFLIGQS

Funkcija[uredi | uredi izvor]

ARID1A je član porodice SWI/SNF, čiji članovi imaju aktivnosti helikaza i ATPaza i smatra se da regulišu transkripciju određenih gena mijenjajući hromatinsku strukturu oko tih gena. Kodirani protein je dio velikog ATP-ovisnog kompleksa za remodeliranje hromatina SWI/SNF, koji je potreban za transkripcijsku aktivaciju gena koji su normalno potisnuti hromatinom. Ima najmanje dva konzervirana domena koji bi mogli biti važne za njegovu funkciju. Prvo, ima ARID domen, koji je DNK-vezujući domen koji može specifično vezati AT-bogatu DNK sekvencu za koju se zna da je prepoznata putem SWI/SNF kompleksa na beta-globinskom lokusu. Drugo, C-terminal proteina može stimulirati glukokortikoidni receptorski zavisnu aktivaciju transkripcije. Smatra se da protein kodiran ovim genom daje specifičnost kompleksu SWI/SNF i može regrutirati kompleks do svojih ciljeva kroz interakcije protein-DNK ili protein-protein. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju različite izoforme.[7]

Klinički značaj[uredi | uredi izvor]

Ovaj gen je obično mutiran u karcinomima želuca,[9] ćelijama raka jajnika,[10] i raka gušterače.[11] U raku dojke udaljene metastaze dobijaju inaktivacijske mutacije u ARID1A koje se ne vide u primarnom tumoru, a smanjena ekspresija ARID1A daje rezistenciju na različite lijekove kao što su trastuzumab i mTOR-inhibitori. Ovi nalazi daju obrazloženje zašto tumori akumuliraju mutacije ARID1A-e.[12][13]

Istraživanje[uredi | uredi izvor]

Čini se da nedostatak ovog gena/proteina štiti pacove od nekih vrsta oštećenja jetre.[14]

Interakcije[uredi | uredi izvor]

Pokazalo se da ARID1A ima interakcije sa SMARCB1[15][16] i SMARCA4.[16][17]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000117713 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000007880 - 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.
  5. ^ Takeuchi T, Furihata M, Heng HH, Sonobe H, Ohtsuki Y (juni 1998). "Chromosomal mapping and expression of the human B120 gene". Gene. 213 (1–2): 189–93. doi:10.1016/S0378-1119(98)00194-2. PMID 9630625.
  6. ^ Takeuchi T, Chen BK, Qiu Y, Sonobe H, Ohtsuki Y (decembar 1997). "Molecular cloning and expression of a novel human cDNA containing CAG repeats". Gene. 204 (1–2): 71–7. doi:10.1016/S0378-1119(97)00525-8. PMID 9434167.
  7. ^ a b "Entrez Gene: ARID1A AT rich interactive domain 1A (SWI-like)".
  8. ^ "UniProt, O14497" (jezik: engleski). Pristupljeno 21. 11. 2021.
  9. ^ Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, et al. (oktobar 2011). "Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer". Nature Genetics. 43 (12): 1219–23. doi:10.1038/ng.982. PMID 22037554. S2CID 8884065.
  10. ^ Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, et al. (oktobar 2010). "ARID1A mutations in endometriosis-associated ovarian carcinomas". The New England Journal of Medicine. 363 (16): 1532–43. doi:10.1056/NEJMoa1008433. PMC 2976679. PMID 20942669.
  11. ^ {{ci te journal | vauthors = Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR | display-authors = 6 | title = Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 5 | pages = E252-9 | date = januar 2012 | pmid = 22233809 | pmc = 3277150 | doi = 10.1073/pnas.1114817109 | doi-access = free }}
  12. ^ Berns K, Sonnenblick A, Gennissen A, Brohée S, Hijmans EM, Evers B, et al. (novembar 2016). "Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance". Clinical Cancer Research. 22 (21): 5238–5248. doi:10.1158/1078-0432.CCR-15-2996. PMID 27172896.
  13. ^ Yates LR, Knappskog S, Wedge D, Farmery JH, Gonzalez S, Martincorena I, et al. (august 2017). "Genomic Evolution of Breast Cancer Metastasis and Relapse". Cancer Cell. 32 (2): 169–184.e7. doi:10.1016/j.ccell.2017.07.005. PMC 5559645. PMID 28810143.
  14. ^ "Tissue Regeneration Promoted through Gene Suppression". Genetic Engineering & Biotechnology News. mart 2016.
  15. ^ Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, et al. (februar 2002). "SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones". The Journal of Biological Chemistry. 277 (7): 5498–505. doi:10.1074/jbc.M108702200. PMID 11734557.
  16. ^ a b Wang W, Côté J, Xue Y, Zhou S, Khavari PA, Biggar SR, et al. (oktobar 1996). "Purification and biochemical heterogeneity of the mammalian SWI-SNF complex". The EMBO Journal. 15 (19): 5370–82. doi:10.1002/j.1460-2075.1996.tb00921.x. PMC 452280. PMID 8895581.
  17. ^ Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR (novembar 1998). "Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling". Cell. 95 (5): 625–36. doi:10.1016/S0092-8674(00)81633-5. PMID 9845365. S2CID 3184211.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.