ARID1A

AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.^[5][6][7]

ARID1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RYU
Identifiers
Aliases	ARID1A, B120, BAF250, BAF250a, BM029, C1orf4, ELD, MRD14, OSA1, P270, SMARCF1, hELD, hOSA1, CSS2, AT-rich interaction domain 1A
External IDs	OMIM: 603024; MGI: 1935147; HomoloGene: 21216; GeneCards: ARID1A; OMA:ARID1A - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.11 Start 26,693,236 bp[1] End 26,782,104 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.3 Start 133,679,008 bp[2] End 133,756,769 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bone marrow cell ventricular zone embryo epithelium of colon mucosa of ileum ganglionic eminence caput epididymis corpus epididymis sural nerve trabecular bone Top expressed in zygote secondary oocyte primitive streak lymph node tail of embryo genital tubercle molar primary oocyte human fetus neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding transcription coactivator activity protein binding nuclear receptor binding nucleosome binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nBAF complex SWI/SNF complex nucleoplasm npBAF complex nucleus SWI/SNF superfamily-type complex brahma complex Biological process androgen receptor signaling pathway chromatin remodeling regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II cardiac muscle cell differentiation optic cup formation involved in camera-type eye development placenta blood vessel development negative regulation of transcription by RNA polymerase II toxin transport chromatin organization transcription, DNA-templated nervous system development cardiac chamber development 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 gastrulation embryo implantation stem cell population maintenance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8289 93760 Ensembl ENSG00000117713 ENSMUSG00000007880 UniProt O14497 A2BH40 RefSeq (mRNA) NM_139135 NM_006015 NM_018450 NM_001080819 NM_001363070 RefSeq (protein) NP_006006 NP_624361 NP_001074288 NP_001349999 NP_001388200 NP_001388202 NP_001388204 NP_001388205 Location (UCSC) Chr 1: 26.69 – 26.78 Mb Chr 4: 133.68 – 133.76 Mb PubMed search [3] [4]
Wikidata
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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. The protein has two large intrinsically disordered regions (IDRs) that mediate the interaction with binding partners.^[8] It also possesses at least two conserved domains that are 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. The protein encoded by this gene confers specificity to the SWI/SNF complex and recruits the complex to its targets through either protein-DNA or protein-protein interactions.^[9][10] Two transcript variants encoding different isoforms have been found for this gene.^[7]

Clinical significance

The gene encoding ARID1A is the most frequently mutated SWI/SNF subunit across cancers.^[11] This gene has been commonly found mutated in different cancers leading to loss of function, including gastric cancers,^[12] colon cancer,^[13] ovarian clear cell carcinoma,^[14] liver cancer,^[15] lymphoma^[9] and pancreatic cancer.^[16] 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.^[17][18]

Research

Lack of this gene/protein seems to protect rats from some types of liver damage.^[19]

Interactions

ARID1A interacts with SWI/SNF subunits SMARCB1^[20][21] and SMARCA4.^[21][22] Intrinsically disordered regions of ARID1A enable the SWI/SNF complex to interact with multiple transcription factors through binding of the ARM domain of beta-catenin.^[8]