ARID2

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AT rich interactive domain 2 (ARID, RFX-like)
Identifiers
Symbols ARID2 ; BAF200; p200
External IDs OMIM609539 MGI1924294 HomoloGene14601 GeneCards: ARID2 Gene
RNA expression pattern
PBB GE ARID2 gnf1h01782 at tn.png
PBB GE ARID2 gnf1h01783 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 196528 77044
Ensembl ENSG00000189079 ENSMUSG00000033237
UniProt Q68CP9 E9Q6E3
RefSeq (mRNA) NM_152641 NM_175251
RefSeq (protein) NP_689854 NP_780460
Location (UCSC) Chr 12:
46.12 – 46.3 Mb
Chr 15:
96.29 – 96.4 Mb
PubMed search [1] [2]

AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.[1]

ARID2 is a subunit of the PBAF chromatin-remodeling complex, which facilitates ligand-dependent transcriptional activation by nuclear receptors.[1]

Structure[edit]

The ARID2 protein contains two conserved C-terminal C2H2 zinc fingers motifs, a region rich in the amino acid residues proline and glutamine, a RFX (regulatory factor X)-type winged-helix DNA-binding domain, and a conserved N-terminal AT-rich DNA interaction domain—the last domain for which the protein is named.[2]

Clinical significance[edit]

Mutation studies have revealed ARID2 to be a significant tumor suppressor in many cancer subtypes. ARID2 mutations are prevalent in hepatocellular carcinoma[3] and melanoma.[4][5] Mutations are present in a smaller but significant fraction in a wide range of other tumors.[6] ARID2 mutations are enriched in hepatitis C virus-associated hepatocellular carcinoma in the US and European patient populations compared with the overall mutation frequency.[2]

Model organisms[edit]

The ARID2 gene, located on chromosome 12q in humans, consists of 21 exons; orthologs are known from mouse, rat, cattle, chicken, and mosquito.[2] Model organisms have been used in the study of ARID2 function. A conditional knockout mouse line, called Arid2tm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty six tests were carried out on mutant adult mice and two significant abnormalities were observed.[9] A recessive lethal study found less homozygous mutant embryos during gestation than predicted by Mendelian ratio. In a second study, no homozygous mutant animals survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; these displayed no abnormalities.[9]

References[edit]

  1. ^ a b "Entrez Gene: ARID2 AT rich interactive domain 2 (ARID, RFX-like)". 
  2. ^ a b c Zhao H, Wang J, Han Y, Huang Z, Ying J, Bi X, Zhao J, Fang Y, Zhou H, Zhou J, Li Z, Zhang Y, Yang X, Yan T, Wang L, Torbenson MS, Cai J. (2011). "ARID2: A new tumor suppressor gene in hepatocellular carcinoma". Oncotarget 2 (11): 886–91. PMC 3259997. PMID 22095441. 
  3. ^ Li, M; Zhao, H; Zhang, X; Wood, LD; Anders, RA; Choti, MA; Pawlik, TM; Daniel, HD; Kannangai, R; Offerhaus, GJ; Velculescu, VE; Wang, L; Zhou, S; Vogelstein, B; Hruban, RH; Papadopoulos, N; Cai, J; Torbenson, MS; Kinzler, KW (Aug 7, 2011). "Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma". Nature Genetics 43 (9): 828–9. doi:10.1038/ng.903. PMC 3163746. PMID 21822264. 
  4. ^ Hodis, E; Watson, IR; Kryukov, GV; Arold, ST; Imielinski, M; Theurillat, JP; Nickerson, E; Auclair, D; Li, L; Place, C; Dicara, D; Ramos, AH; Lawrence, MS; Cibulskis, K; Sivachenko, A; Voet, D; Saksena, G; Stransky, N; Onofrio, RC; Winckler, W; Ardlie, K; Wagle, N; Wargo, J; Chong, K; Morton, DL; Stemke-Hale, K; Chen, G; Noble, M; Meyerson, M; Ladbury, JE; Davies, MA; Gershenwald, JE; Wagner, SN; Hoon, DS; Schadendorf, D; Lander, ES; Gabriel, SB; Getz, G; Garraway, LA; Chin, L (2012). "A landscape of driver mutations in melanoma". Cell 150 (2): 251–63. doi:10.1016/j.cell.2012.06.024. PMC 3600117. PMID 22817889. 
  5. ^ Krauthammer, M; Kong, Y; Ha, BH; Evans, P; Bacchiocchi, A; McCusker, JP; Cheng, E; Davis, MJ; Goh, G; Choi, M; Ariyan, S; Narayan, D; Dutton-Regester, K; Capatana, A; Holman, EC; Bosenberg, M; Sznol, M; Kluger, HM; Brash, DE; Stern, DF; Materin, MA; Lo, RS; Mane, S; Ma, S; Kidd, KK; Hayward, NK; Lifton, RP; Schlessinger, J; Boggon, TJ; Halaban, R (2012). "Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma". Nature Genetics 44 (9): 1006–14. doi:10.1038/ng.2359. PMC 3432702. PMID 22842228. 
  6. ^ Shain, AH; Pollack, JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers.". PLoS ONE 8 (1): e55119. doi:10.1371/journal.pone.0055119. PMC 3552954. PMID 23355908. 
  7. ^ "Salmonella infection data for Arid2". Wellcome Trust Sanger Institute. 
  8. ^ "Citrobacter infection data for Arid2". Wellcome Trust Sanger Institute. 
  9. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  10. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ^ "International Knockout Mouse Consortium". 
  12. ^ "Mouse Genome Informatics". 
  13. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  14. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  15. ^ Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  16. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: Revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.