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Gene Review

SRCAP  -  Snf2-related CREBBP activator protein

Homo sapiens

Synonyms: DOMO1, Domino homolog 2, EAF1, FLHS, Helicase SRCAP, ...
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Disease relevance of SRCAP

  • Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP [1].
  • These data suggest a novel mechanism of adenovirus host cell control by which DBP binds to and inactivates SrCap, a member of the SNF2 chromatin-remodeling protein family [2].

High impact information on SRCAP


Biological context of SRCAP

  • Transfection experiments demonstrate that SRCAP is able to activate transcription when expressed as a Gal-SRCAP chimera and that SRCAP also enhances the ability of CBP to activate transcription [5].
  • In various cell types, SRCAP is found in distinct multiprotein complexes that include proteins found in SWI/SNF chromatin remodeling complexes [6].
  • We show that human SRCAP complements recessive domino mutant phenotypes [4].
  • SRCAP colocalizes extensively with DOM on Drosophila polytene chromosomes and is recruited to sites of active transcription, such as steroid-regulated loci, but not to activated heat shock loci [4].
  • However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP [1].

Associations of SRCAP with chemical compounds

  • Our current studies demonstrate that SRCAP enhances phosphoenolpyruvate carboxykinase promoter transcription induced by glucocorticoids [6].
  • The highest levels of SRCAP were observed on the active SP-1, G3BP, and FAD synthetase promoters [7].

Physical interactions of SRCAP

  • SRCAP was identified by its ability to bind to CBP and was found to potentiate the ability of CBP to activate transcription [6].
  • We have previously demonstrated that the Adenovirus 2 DNA Binding Protein (DBP) binds to SrCap and inhibits the transcription mediated by the carboxyl-terminal region of SrCap (amino acids 1275-2971) [8].

Enzymatic interactions of SRCAP

  • Mechanistic studies revealed that the human INO80 complex catalyzes nucleosome sliding and the SRCAP complex catalyzes ATP-dependent exchange of histone H2A/H2B dimers containing the histone variant H2A.Z into nucleosomes [9].

Regulatory relationships of SRCAP


Other interactions of SRCAP

  • We propose that SRCAP, by virtue of its ability to interact with CBP, functions as a coactivator to regulate transcription initiated by several signaling pathways [6].
  • In similar studies, SRCAP was also found to serve as a coactivator for the androgen receptor [6].
  • Studies in our laboratory have demonstrated that SRCAP functions as a coactivator for CREB-mediated transcription of a number of promoters, including that of the phosphoenolpyruvate carboxykinase gene [6].
  • We also found that DBP has no effect on transcription mediated by a transcriptional activator that is not related to SrCap, indicating that our reported transcriptional inhibition is specific for SrCap and not due to nonspecific effects of DBP's DNA binding activity on the CAT reporter plasmid [8].

Analytical, diagnostic and therapeutic context of SRCAP


  1. Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. Ghosh, A.K., Majumder, M., Steele, R., Yaciuk, P., Chrivia, J., Ray, R., Ray, R.B. J. Biol. Chem. (2000) [Pubmed]
  2. Adenovirus DNA binding protein interacts with the SNF2-related CBP activator protein (SrCap) and inhibits SrCap-mediated transcription. Xu, X., Chackalaparampil, I., Monroy, M.A., Cannella, M.T., Pesek, E., Chrivia, J., Yaciuk, P. J. Virol. (2001) [Pubmed]
  3. GAS41 is required for repression of the p53 tumor suppressor pathway during normal cellular proliferation. Park, J.H., Roeder, R.G. Mol. Cell. Biol. (2006) [Pubmed]
  4. Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Eissenberg, J.C., Wong, M., Chrivia, J.C. Mol. Cell. Biol. (2005) [Pubmed]
  5. Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. Johnston, H., Kneer, J., Chackalaparampil, I., Yaciuk, P., Chrivia, J. J. Biol. Chem. (1999) [Pubmed]
  6. SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Monroy, M.A., Schott, N.M., Cox, L., Chen, J.D., Ruh, M., Chrivia, J.C. Mol. Endocrinol. (2003) [Pubmed]
  7. The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. Wong, M.M., Cox, L.K., Chrivia, J.C. J. Biol. Chem. (2007) [Pubmed]
  8. Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription. Xu, X., Tarakanova, V., Chrivia, J., Yaciuk, P. Virology (2003) [Pubmed]
  9. Purification and assay of the human INO80 and SRCAP chromatin remodeling complexes. Cai, Y., Jin, J., Gottschalk, A.J., Yao, T., Conaway, J.W., Conaway, R.C. Methods (2006) [Pubmed]
  10. Molecular cloning and characterization of an SRCAP chromatin remodeling homologue in Toxoplasma gondii. Sullivan, W.J., Monroy, M.A., Bohne, W., Nallani, K.C., Chrivia, J., Yaciuk, P., Smith, C.K., Queener, S.F. Parasitol. Res. (2003) [Pubmed]
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