Biology:ARID1A
 Generic protein structure example |
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.[1][2][3]
Function
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SWI/SNF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene.[3]
Clinical significance
This gene has been commonly found mutated in gastric cancers,[4] ovarian clear cell carcinoma,[5] and pancreatic cancer.[6] In breast cancer distant metastases acquire inactivation mutations in ARID1A not seen in the primary tumor, and reduced ARID1A expression confers resistance to different drugs such as trastuzumab and mTOR inhibitors. These findings provide a rationale for why tumors accumulate ARID1A mutations.[7][8]
Research
Lack of this gene/protein seems to protect rats from some types of liver damage.[9]
Interactions
ARID1A has been shown to interact with SMARCB1[10][11] and SMARCA4.[11][12]
References
- ↑ "Chromosomal mapping and expression of the human B120 gene". Gene 213 (1–2): 189–93. June 1998. doi:10.1016/S0378-1119(98)00194-2. PMID 9630625.
- ↑ "Molecular cloning and expression of a novel human cDNA containing CAG repeats". Gene 204 (1–2): 71–7. December 1997. doi:10.1016/S0378-1119(97)00525-8. PMID 9434167.
- ↑ 3.0 3.1 "Entrez Gene: ARID1A AT rich interactive domain 1A (SWI-like)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8289.
- ↑ "Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer". Nature Genetics 43 (12): 1219–23. October 2011. doi:10.1038/ng.982. PMID 22037554.
- ↑ "ARID1A mutations in endometriosis-associated ovarian carcinomas". The New England Journal of Medicine 363 (16): 1532–43. October 2010. doi:10.1056/NEJMoa1008433. PMID 20942669.
- ↑ "Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer". Proceedings of the National Academy of Sciences of the United States of America 109 (5): E252-9. January 2012. doi:10.1073/pnas.1114817109. PMID 22233809.
- ↑ "Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance". Clinical Cancer Research 22 (21): 5238–5248. November 2016. doi:10.1158/1078-0432.CCR-15-2996. PMID 27172896.
- ↑ "Genomic Evolution of Breast Cancer Metastasis and Relapse". Cancer Cell 32 (2): 169–184.e7. August 2017. doi:10.1016/j.ccell.2017.07.005. PMID 28810143.
- ↑ "Tissue Regeneration Promoted through Gene Suppression". Genetic Engineering & Biotechnology News. March 2016. http://www.genengnews.com/gen-news-highlights/tissue-regeneration-promoted-through-gene-suppression/81252529/.
- ↑ "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. February 2002. doi:10.1074/jbc.M108702200. PMID 11734557.
- ↑ 11.0 11.1 "Purification and biochemical heterogeneity of the mammalian SWI-SNF complex". The EMBO Journal 15 (19): 5370–82. October 1996. doi:10.1002/j.1460-2075.1996.tb00921.x. PMID 8895581.
- ↑ "Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling". Cell 95 (5): 625–36. November 1998. doi:10.1016/S0092-8674(00)81633-5. PMID 9845365.
Further reading
- "Recent advances in understanding chromatin remodeling by Swi/Snf complexes". Current Opinion in Genetics & Development 13 (2): 136–42. April 2003. doi:10.1016/S0959-437X(03)00022-4. PMID 12672490.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Diversity and specialization of mammalian SWI/SNF complexes". Genes & Development 10 (17): 2117–30. September 1996. doi:10.1101/gad.10.17.2117. PMID 8804307.
- "Purification and biochemical heterogeneity of the mammalian SWI-SNF complex". The EMBO Journal 15 (19): 5370–82. October 1996. doi:10.1002/j.1460-2075.1996.tb00921.x. PMID 8895581.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "p300/CREB binding protein-related protein p270 is a component of mammalian SWI/SNF complexes". Molecular and Cellular Biology 18 (6): 3596–603. June 1998. doi:10.1128/MCB.18.6.3596. PMID 9584200.
- "The human SWI-SNF complex protein p270 is an ARID family member with non-sequence-specific DNA binding activity". Molecular and Cellular Biology 20 (9): 3137–46. May 2000. doi:10.1128/MCB.20.9.3137-3146.2000. PMID 10757798.
- "A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex". Molecular and Cellular Biology 20 (23): 8879–88. December 2000. doi:10.1128/MCB.20.23.8879-8888.2000. PMID 11073988.
- "Expression of SMARCF1, a truncated form of SWI1, in neuroblastoma". The American Journal of Pathology 158 (2): 663–72. February 2001. doi:10.1016/S0002-9440(10)64008-4. PMID 11159203.
- "Characterization of mammalian orthologues of the Drosophila osa gene: cDNA cloning, expression, chromosomal localization, and direct physical interaction with Brahma chromatin-remodeling complex". Genomics 73 (2): 140–8. April 2001. doi:10.1006/geno.2001.6477. PMID 11318604.
- "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. February 2002. doi:10.1074/jbc.M108702200. PMID 11734557.
- "Selectivity of chromatin-remodelling cofactors for ligand-activated transcription". Nature 414 (6866): 924–8. 2002. doi:10.1038/414924a. PMID 11780067.
- "Cloning and characterization of hELD/OSA1, a novel BRG1 interacting protein". The Biochemical Journal 364 (Pt 1): 255–64. May 2002. doi:10.1042/bj3640255. PMID 11988099.
- "Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors". The Journal of Biological Chemistry 277 (44): 41674–85. November 2002. doi:10.1074/jbc.M205961200. PMID 12200431.
- "Novel SWI/SNF chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner". Molecular and Cellular Biology 23 (8): 2942–52. April 2003. doi:10.1128/MCB.23.8.2942-2952.2003. PMID 12665591.
- "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell 113 (7): 905–17. June 2003. doi:10.1016/S0092-8674(03)00436-7. PMID 12837248.
External links
- ARID1A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human ARID1A genome location and ARID1A gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: O14497 (AT-rich interactive domain-containing protein 1A) at the PDBe-KB.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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