ARID4A (AT-rich interaction domain 4A)

Gene

• Entrez ID: 5926
• Gene name: AT-rich interaction domain 4A
• Gene symbol: ARID4A
• Synonyms: RBBP-1, RBBP1, RBP-1, RBP1
• Chromosome: 14
• Chromosome location: 14q23.1
• Summary: The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs62621193	G>A,C	Conflicting-interpretations-of-pathogenicity	Splice donor variant, genic downstream transcript variant, coding sequence variant, missense variant
rs1594966387	G>T	Likely-pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018511	hsa-miR-335-5p	Microarray	18185580
MIRT030996	hsa-miR-21-5p	Microarray	18591254
MIRT624663	hsa-miR-548as-3p	HITS-CLIP	23824327
MIRT624664	hsa-miR-548z	HITS-CLIP	23824327
MIRT624665	hsa-miR-548h-3p	HITS-CLIP	23824327
MIRT624666	hsa-miR-548d-3p	HITS-CLIP	23824327
MIRT624667	hsa-miR-548bb-3p	HITS-CLIP	23824327
MIRT624668	hsa-miR-548ac	HITS-CLIP	23824327
MIRT660532	hsa-miR-6771-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IBA	21873635
GO:0003677	Function	DNA binding	IDA	15640446
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IDA
GO:0006349	Process	Regulation of gene expression by genetic imprinting	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007283	Process	Spermatogenesis	IEA
GO:0017053	Component	Transcription repressor complex	IDA	11283269
GO:0034773	Process	Histone H4-K20 trimethylation	IEA
GO:0036124	Process	Histone H3-K9 trimethylation	IEA
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	12724404
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048821	Process	Erythrocyte development	IEA
GO:0080182	Process	Histone H3-K4 trimethylation	IEA
GO:0097368	Process	Establishment of Sertoli cell barrier	IEA

Other IDs

• MIM: 180201
• HGNC: 9885
• e!Ensembl: ENSG00000032219

Protein

• UniProt ID: P29374
• Protein name: AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1)
• Protein function: DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity).
• PDB: 2LCC, 2MAM, 2YRV, 6BPH, 6L87
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08169	RBB1NT	170 → 262	RBB1NT (NUC162) domain	Domain
  PF01388	ARID	311 → 397	ARID/BRIGHT DNA binding domain	Domain
  PF11717	Tudor-knot	574 → 630	RNA binding activity-knot of a chromodomain	Family

• Sequence:

  MKAADEPAYLTVGTDVSAKYRGAFCEAKIKTVKRLVKVKVLLKQDNTTQLVQDDQVKGPL
  RVGAIVETRTSDGSFQEAIISKLTDASWYTVVFDDGDERTLRRTSLCLKGERHFAESETL
  DQLPLTNPEHFGTPVIAKKTNRGRRSSLPVTEDEKEEESSEEEDEDKRRLNDELLGKVVS
  VVSATERTEWYPALVISPSCNDDITVKKDQCLVRSFIDSKFYSIARKDIKEVDILNLPES
  ELSTKPGLQKASIFLKTRVVPDNWKMDISEILESSSSDDEDGPAEENDEEKEKEAKKTEE
  EVPEEELDPEERDNFLQQLYKFMEDRGTPINKPPVLGYKDLNLFKLFRLVYHQGGCDNID
  SGAVWKQIYMDLGIPILNSAASYNVKTAYRKYLYGFEEYCRSANIQFRTVHHHEPKVKEE
  KKDLEESMEEALKLDQEMPLTEVKSEPEENIDSNSESEREEIELKSPRGRRRIARDVNSI
  KKEIEEEKTEDKLKDNDTENKDVDDDYETAEKKENELLLGRKNTPKQKEKKIKKQEDSDK
  DSDEEEEKSQEREETESKCDSEGEEDEEDMEPCLTGTKVKVKYGRGKTQKIYEASIKSTE
  IDDGEVLYLVHYYGWNVRYDEWVKADRIIWPLDKGGPKKKQKKKAKNKEDSEKDEKRDEE
  RQKSKRGRPPLKSTLSSNMPYGLSKTANSEGKSDSCSSDSETEDALEKNLINEELSLKDE
  LEKNENLNDDKLDEENPKISAHILKENDRTQMQPLETLKLEVGENEQIVQIFGNKMEKTE
  EVKKEAEKSPKGKGRRSKTKDLSLEIIKISSFGQNEAGSEPHIEAHSLELSSLDNKNFSS
  ATEDEIDQCVKEKKLKRKILGQSSPEKKIRIENGMEMTNTVSQERTSDCIGSEGMKNLNF
  EQHFERENEGMPSLIAESNQCIQQLTSERFDSPAEETVNIPLKEDEDAMPLIGPETLVCH
  EVDLDDLDEKDKTSIEDVAVESSESNSLVSIPPALPPVVQHNFSVASPLTLSQDESRSVK
  SESDITIEVDSIAEESQEGLCERESANGFETNVASGTCSIIVQERESREKGQKRPSDGNS
  GLMAKKQKRTPKRTSAAAKNEKNGTGQSSDSEDLPVLDNSSKCTPVKHLNVSKPQKLARS
  PARISPHIKDGEKDKHREKHPNSSPRTYKWSFQLNELDNMNSTERISFLQEKLQEIRKYY
  MSLKSEVATIDRRRKRLKKKDREVSHAGASMSSASSDTGMSPSSSSPPQNVLAVECR

• Sequence length: 1257

Pathways

Reactome:

HDACs deacetylate histones

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	29610475

Unknown
Disease name	Disease term	dbSNP ID	References
Prostatic neoplasms	Prostatic Neoplasms		29610475