PCAF

P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53.

KAT2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CM0, 1JM4, 1N72, 1WUG, 1WUM, 1ZS5, 2RNW, 2RNX, 3GG3, 4NSQ, 5FE2, 5FE4, 5FDZ, 5FE8, 5FE5, 5FE1, 5FE7, 5FE9, 5FE3, 5FE0, 5FE6
Identifiers
Aliases	KAT2B, CAF, P/CAF, PCAF, lysine acetyltransferase 2B
External IDs	OMIM: 602303; MGI: 1343094; HomoloGene: 20834; GeneCards: KAT2B; OMA:KAT2B - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3p24.3 Start 20,040,446 bp End 20,154,404 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 C|17 27.86 cM Start 53,873,889 bp End 53,979,748 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in external globus pallidus trabecular bone buccal mucosa cell corpus callosum Achilles tendon subthalamic nucleus pars reticulata amniotic fluid Skeletal muscle tissue of rectus abdominis pars compacta Top expressed in retinal pigment epithelium nasal epithelium olfactory epithelium Epithelium of choroid plexus iris seminal vesicula vestibular membrane of cochlear duct gastrula extensor digitorum longus muscle ankle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription coregulator activity protein binding acyltransferase activity histone acetyltransferase activity cyclin-dependent protein serine/threonine kinase inhibitor activity protein kinase binding chromatin binding lysine N-acetyltransferase activity, acting on acetyl phosphate as donor transcription coactivator activity transcription factor binding histone deacetylase binding acetyltransferase activity protein-containing complex binding peptide-lysine-N-acetyltransferase activity diamine N-acetyltransferase activity Cellular component I band nucleoplasm histone acetyltransferase complex A band actomyosin kinetochore nucleus cytoplasm centrosome microtubule organizing center cytoskeleton protein-containing complex Biological process Notch signaling pathway regulation of protein ADP-ribosylation epigenetic maintenance of chromatin in transcription-competent conformation chromatin remodeling regulation of transcription, DNA-templated negative regulation of cyclin-dependent protein serine/threonine kinase activity rhythmic process N-terminal peptidyl-lysine acetylation transcription, DNA-templated positive regulation of transcription, DNA-templated histone acetylation histone H3 acetylation cellular response to insulin stimulus histone H3-K9 acetylation cell cycle transcription initiation from RNA polymerase II promoter viral process peptidyl-lysine acetylation negative regulation of cell population proliferation positive regulation of transcription by RNA polymerase II internal peptidyl-lysine acetylation regulation of megakaryocyte differentiation protein acetylation positive regulation of transcription of Notch receptor target heart development positive regulation of Notch signaling pathway negative regulation of centriole replication limb development protein deubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8850 18519 Ensembl ENSG00000114166 ENSMUSG00000000708 UniProt Q92831 Q9JHD1 RefSeq (mRNA) NM_003884 NM_001190846 NM_020005 RefSeq (protein) NP_003875 NP_001177775 NP_064389 Location (UCSC) Chr 3: 20.04 – 20.15 Mb Chr 17: 53.87 – 53.98 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Structure

Several domains of PCAF can act independently or in unison to enable its functions. PCAF has separate acetyltransferase and E3 ubiquitin ligase domains as well as a bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination.

Function

CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by the PCAF gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.

Regulation

The acetyltransferase activity and cellular location of PCAF are regulated through acetylation of PCAF itself. PCAF may be autoacetylated (acetylated by itself) or by p300. Acetylation leads to migration to the nucleus and enhances its acetyltransferase activity. PCAF interacts with and is deacetylated by HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.

Protein interactions

PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by ATF to acetylate histones and promote transcription of ATF4 target genes.

Targets

There are various protein targets of PCAF's acetyltransferase activity including transcription factors such as Fli1, p53 and numerous histone residues. Hdm2, itself a ubiquitin ligase that targets p53, has also been demonstrated to be a target of the ubiquitin-ligase activity of PCAF.

Interactions

PCAF has been shown to interact with:

• BRCA2,
• CTNNB1,
• CREBBP,
• EVI1,
• HNF1A,
• IRF1,
• IRF2,
• KLF13,
• Mdm2
• Myc,
• NCOA1,
• POLR2A,
• RBPJ,
• TCF3,
• TRRAP, and
• TWIST1.

See also

• Transcription coregulator
• Acetyltransferase

External links

• PCAF protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C105

Further reading

• Marcello A, Zoppé M, Giacca M (2002). "Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator". IUBMB Life. 51 (3): 175–81. doi:10.1080/152165401753544241. PMID 11547919. S2CID 10931640.
• Ott M, Dorr A, Hetzer-Egger C, Kaehlcke K, Schnolzer M, Henklein P, Cole P, Zhou MM, Verdin E (2004). "Tat Acetylation: A Regulatory Switch between Early and Late Phases in HIV Transcription Elongation". Reversible Protein Acetylation. Novartis Foundation Symposia. Vol. 259. pp. 182–93, discussion 193–6, 223–5. doi:10.1002/0470862637.ch13. ISBN 978-0-470-86263-6. PMID 15171254.
• Liou LY, Herrmann CH, Rice AP (2005). "HIV-1 infection and regulation of Tat function in macrophages". Int. J. Biochem. Cell Biol. 36 (9): 1767–75. doi:10.1016/j.biocel.2004.02.018. PMID 15183343.
• Gibellini D, Vitone F, Schiavone P, Re MC (2005). "HIV-1 tat protein and cell proliferation and survival: a brief review". New Microbiol. 28 (2): 95–109. PMID 16035254.
• Hetzer C, Dormeyer W, Schnölzer M, Ott M (2006). "Decoding Tat: the biology of HIV Tat posttranslational modifications". Microbes Infect. 7 (13): 1364–9. doi:10.1016/j.micinf.2005.06.003. PMID 16046164.
• Peruzzi F (2006). "The multiple functions of HIV-1 Tat: proliferation versus apoptosis". Front. Biosci. 11: 708–17. doi:10.2741/1829. PMID 16146763.
• Stevens M, De Clercq E, Balzarini J (2007). "The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention". Med Res Rev. 26 (5): 595–625. doi:10.1002/med.20081. PMC 7168390. PMID 16838299.
• Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets. 7 (12): 1595–606. doi:10.2174/138945006779025338. PMID 17168834.
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
• Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y (1996). "A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A". Nature. 382 (6589): 319–24. Bibcode:1996Natur.382..319Y. doi:10.1038/382319a0. PMID 8684459. S2CID 4328685.
• Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1997). "The transcriptional coactivators p300 and CBP are histone acetyltransferases". Cell. 87 (5): 953–9. doi:10.1016/S0092-8674(00)82001-2. PMID 8945521. S2CID 2624456.
• Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, O'Malley BW (1997). "Steroid receptor induction of gene transcription: a two-step model". Proc. Natl. Acad. Sci. U.S.A. 94 (15): 7879–84. Bibcode:1997PNAS...94.7879J. doi:10.1073/pnas.94.15.7879. PMC 21523. PMID 9223281.
• Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (1997). "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell. 90 (3): 569–80. doi:10.1016/S0092-8674(00)80516-4. PMID 9267036. S2CID 15284825.
• Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW (1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature. 389 (6647): 194–8. Bibcode:1997Natur.389..194S. doi:10.1038/38304. PMID 9296499. S2CID 4404530.
• Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (1997). "TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1". J. Biol. Chem. 272 (44): 27629–34. doi:10.1074/jbc.272.44.27629. PMID 9346901.
• Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG (1998). "Transcription factor-specific requirements for coactivators and their acetyltransferase functions". Science. 279 (5351): 703–7. Bibcode:1998Sci...279..703K. doi:10.1126/science.279.5351.703. PMID 9445475.
• Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y, Levrero M (1998). "Differential roles of p300 and PCAF acetyltransferases in muscle differentiation". Mol. Cell. 1 (1): 35–45. doi:10.1016/S1097-2765(00)80005-2. PMID 9659901.
• Ogryzko VV, Kotani T, Zhang X, Schiltz RL, Howard T, Yang XJ, Howard BH, Qin J, Nakatani Y (1998). "Histone-like TAFs within the PCAF histone acetylase complex". Cell. 94 (1): 35–44. doi:10.1016/S0092-8674(00)81219-2. PMID 9674425. S2CID 18942972.
• Randhawa GS, Bell DW, Testa JR, Feinberg AP (1998). "Identification and mapping of human histone acetylation modifier gene homologues". Genomics. 51 (2): 262–9. doi:10.1006/geno.1998.5370. PMID 9722949.
• Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatani Y, Jeang KT (1998). "Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat". J. Biol. Chem. 273 (38): 24898–905. doi:10.1074/jbc.273.38.24898. PMID 9733796.

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