ARID4A

AT rich interactive domain 4A (RBP1-like)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LCC​, 2MAM​, 2YRV​
Identifiers
Symbols	ARID4A ; RBBP-1; RBBP1; RBP-1; RBP1
External IDs	OMIM: 180201 MGI: 2444354 HomoloGene: 11303 GeneCards: ARID4A Gene
Gene ontology Molecular function • DNA binding • transcription factor activity, sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nucleus • nucleoplasm • transcriptional repressor complex Biological process • chromatin organization • regulation of gene expression by genetic imprinting • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • spermatogenesis • histone H4-K20 trimethylation • histone H3-K9 trimethylation • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • erythrocyte development • histone H3-K4 trimethylation • establishment of Sertoli cell barrier Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5926	238247
Ensembl	ENSG00000032219	ENSMUSG00000048118
UniProt	P29374	E9Q9V1
RefSeq (mRNA)	NM_002892	NM_001081195
RefSeq (protein)	NP_002883	NP_001074664
Location (UCSC)	Chr 14: 58.3 – 58.37 Mb	Chr 12: 71.02 – 71.1 Mb
PubMed search

AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.^[1][2][3]

Function

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.^[1]

Model organisms

Arid4a knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Abnormal[4]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Abnormal[5]
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal[6]
Radiography	Abnormal[7]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[8]
Haematology	Abnormal[9]
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of ARID4A function. A conditional knockout mouse line, called Arid4a^{tm1a(EUCOMM)Wtsi[14][15]} 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 — at the Wellcome Trust Sanger Institute.^[16][17][18] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[12][19]

Twenty five tests were carried out and nine phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than expected, and in a separate study less than the predicted Mendelian ratio survived until weaning. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by DEXA, displayed vertebral fusion and had clinical chemistry abnormalities including hypoalbuminemia and decreased circulating fructosamine levels. They also had haematological defects and an increased NK cell number.^[12]

Interactions

ARID4A has been shown to interact with Retinoblastoma protein.^[20]

References

1. "Entrez Gene: ARID4A AT rich interactive domain 4A (RBP1-like)".
2. Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE, Oliff A (Jul 1991). "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product". Nature 352 (6332): 251–4. doi:10.1038/352251a0. PMID 1857421.
3. Otterson GA, Kratzke RA, Lin AY, Johnston PG, Kaye FJ (Apr 1993). "Alternative splicing of the RBP1 gene clusters in an internal exon that encodes potential phosphorylation sites". Oncogene 8 (4): 949–57. PMID 8455946.
4. "Body weight data for Arid4a". Wellcome Trust Sanger Institute.
5. "Grip strength data for Arid4a". Wellcome Trust Sanger Institute.
6. "DEXA data for Arid4a". Wellcome Trust Sanger Institute.
7. "Radiography data for Arid4a". Wellcome Trust Sanger Institute.
8. "Clinical chemistry data for Arid4a". Wellcome Trust Sanger Institute.
9. "Haematology data for Arid4a". Wellcome Trust Sanger Institute.
10. "Salmonella infection data for Arid4a". Wellcome Trust Sanger Institute.
11. "Citrobacter infection data for Arid4a". Wellcome Trust Sanger Institute.
12. 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.
13. Mouse Resources Portal, Wellcome Trust Sanger Institute.
14. "International Knockout Mouse Consortium".
15. "Mouse Genome Informatics".
16. 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.
17. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
18. 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.
19. 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.
20. Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE (Oct 1999). "RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins". Molecular and Cellular Biology 19 (10): 6632–41. doi:10.1128/mcb.19.10.6632. PMC 84642. PMID 10490602.

Further reading

• Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE, Oliff A (Jul 1991). "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product". Nature 352 (6332): 251–4. doi:10.1038/352251a0. PMID 1857421.
• Fattaey AR, Helin K, Dembski MS, Dyson N, Harlow E, Vuocolo GA, Hanobik MG, Haskell KM, Oliff A, Defeo-Jones D (Nov 1993). "Characterization of the retinoblastoma binding proteins RBP1 and RBP2". Oncogene 8 (11): 3149–56. PMID 8414517.
• Otterson GA, Kratzke RA, Lin AY, Johnston PG, Kaye FJ (Apr 1993). "Alternative splicing of the RBP1 gene clusters in an internal exon that encodes potential phosphorylation sites". Oncogene 8 (4): 949–57. PMID 8455946.
• Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K, Benarous R (Mar 1998). "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif". Molecular Cell 1 (4): 565–74. doi:10.1016/S1097-2765(00)80056-8. PMID 9660940.
• Lai A, Marcellus RC, Corbeil HB, Branton PE (Mar 1999). "RBP1 induces growth arrest by repression of E2F-dependent transcription". Oncogene 18 (12): 2091–100. doi:10.1038/sj.onc.1202520. PMID 10321733.
• Cao J, Gao T, Giuliano AE, Irie RF (Feb 1999). "Recognition of an epitope of a breast cancer antigen by human antibody". Breast Cancer Research and Treatment 53 (3): 279–90. doi:10.1023/A:1006115922401. PMID 10369074.
• Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE (Oct 1999). "RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins". Molecular and Cellular Biology 19 (10): 6632–41. doi:10.1128/mcb.19.10.6632. PMC 84642. PMID 10490602.
• Lai A, Kennedy BK, Barbie DA, Bertos NR, Yang XJ, Theberge MC, Tsai SC, Seto E, Zhang Y, Kuzmichev A, Lane WS, Reinberg D, Harlow E, Branton PE (Apr 2001). "RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest". Molecular and Cellular Biology 21 (8): 2918–32. doi:10.1128/MCB.21.8.2918-2932.2001. PMC 86920. PMID 11283269.
• Fleischer TC, Yun UJ, Ayer DE (May 2003). "Identification and characterization of three new components of the mSin3A corepressor complex". Molecular and Cellular Biology 23 (10): 3456–67. doi:10.1128/MCB.23.10.3456-3467.2003. PMC 164750. PMID 12724404.
• Meehan WJ, Samant RS, Hopper JE, Carrozza MJ, Shevde LA, Workman JL, Eckert KA, Verderame MF, Welch DR (Jan 2004). "Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription". The Journal of Biological Chemistry 279 (2): 1562–9. doi:10.1074/jbc.M307969200. PMID 14581478.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Monroe DG, Secreto FJ, Hawse JR, Subramaniam M, Khosla S, Spelsberg TC (Sep 2006). "Estrogen receptor isoform-specific regulation of the retinoblastoma-binding protein 1 (RBBP1) gene: roles of AF1 and enhancer elements". The Journal of Biological Chemistry 281 (39): 28596–604. doi:10.1074/jbc.M605226200. PMID 16873370.

External links

• ARID4A protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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