ARID2

AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.[5]

ARID2
Identifiers
AliasesARID2, BAF200, p200, AT-rich interaction domain 2, CSS6
External IDsOMIM: 609539 MGI: 1924294 HomoloGene: 14601 GeneCards: ARID2
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q12Start45,729,706 bp[1]
End45,908,040 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

196528

77044

Ensembl

ENSG00000189079

ENSMUSG00000033237

UniProt

Q68CP9

E9Q7E2

RefSeq (mRNA)

NM_152641
NM_001347839

NM_175251

RefSeq (protein)

NP_001334768
NP_689854

NP_780460

Location (UCSC)Chr 12: 45.73 – 45.91 MbChr 15: 96.29 – 96.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

ARID2 is a subunit of the PBAF chromatin-remodeling complex, which facilitates ligand-dependent transcriptional activation by nuclear receptors.[5]

Structure

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.[6]

Clinical significance

Mutation studies have revealed ARID2 to be a significant tumor suppressor in many cancer subtypes. ARID2 mutations are prevalent in hepatocellular carcinoma[7] and melanoma.[8][9] Mutations are present in a smaller but significant fraction in a wide range of other tumors.[10] ARID2 mutations are enriched in hepatitis C virus-associated hepatocellular carcinoma in the US and European patient populations compared with the overall mutation frequency.[6]

Model organisms

The ARID2 gene, located on chromosome 12q in humans, consists of 21 exons; orthologs are known from mouse, rat, cattle, chicken, and mosquito.[6] Model organisms have been used in the study of ARID2 function. A conditional knockout mouse line, called Arid2tm1a(EUCOMM)Wtsi[15][16] 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.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty six tests were carried out on mutant adult mice and two significant abnormalities were observed.[13] A recessive lethal study found fewer 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.[13]

References
  1. GRCh38: Ensembl release 89: ENSG00000189079 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000033237 - Ensembl, May 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. "Entrez Gene: ARID2 AT rich interactive domain 2 (ARID, RFX-like)".
  6. 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 (Nov 2011). "ARID2: a new tumor suppressor gene in hepatocellular carcinoma". Oncotarget. 2 (11): 886–91. doi:10.18632/oncotarget.355. PMC 3259997. PMID 22095441.
  7. 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 (Sep 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.
  8. 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 (Jul 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.
  9. 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 (Sep 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.
  10. Shain AH, Pollack JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers". PLOS ONE. 8 (1): e55119. Bibcode:2013PLoSO...855119S. doi:10.1371/journal.pone.0055119. PMC 3552954. PMID 23355908.
  11. "Salmonella infection data for Arid2". Wellcome Trust Sanger Institute.
  12. "Citrobacter infection data for Arid2". Wellcome Trust Sanger Institute.
  13. 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. S2CID 85911512.
  14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  15. "International Knockout Mouse Consortium".
  16. "Mouse Genome Informatics".
  17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  18. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  19. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

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