Histone acetyltransferase KAT5

Details

Name
Histone acetyltransferase KAT5
Synonyms
  • 2.3.1.48
  • 60 kDa Tat-interactive protein
  • cPLA(2)-interacting protein
  • Histone acetyltransferase HTATIP
  • HIV-1 Tat interactive protein
  • HTATIP
  • Lysine acetyltransferase 5
  • TIP60
Gene Name
KAT5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009499|Histone acetyltransferase KAT5
MAEVGEIIEGCRLPVLRRNQDNEDEWPLAEILSVKDISGRKLFYVHYIDFNKRLDEWVTH
ERLDLKKIQFPKKEAKTPTKNGLPGSRPGSPEREVPASAQASGKTLPIPVQITLRFNLPK
EREAIPGGEPDQPLSSSSCLQPNHRSTKRKVEVVSPATPVPSETAPASVFPQNGAARRAV
AAQPGRKRKSNCLGTDEDSQDSSDGIPSAPRMTGSLVSDRSHDDIVTRMKNIECIELGRH
RLKPWYFSPYPQELTTLPVLYLCEFCLKYGRSLKCLQRHLTKCDLRHPPGNEIYRKGTIS
FFEIDGRKNKSYSQNLCLLAKCFLDHKTLYYDTDPFLFYVMTEYDCKGFHIVGYFSKEKE
STEDYNVACILTLPPYQRRGYGKLLIEFSYELSKVEGKTGTPEKPLSDLGLLSYRSYWSQ
TILEILMGLKSESGERPQITINEISEITSIKKEDVISTLQYLNLINYYKGQYILTLSEDI
VDGHERAMLKRLLRIDSKCLHFTPKDWSKRGKW
Number of residues
513
Molecular Weight
58581.45
Theoretical pI
Not Available
GO Classification
Functions
acetyltransferase activity / androgen receptor binding / histone acetyltransferase activity / metal ion binding / repressing transcription factor binding / transcription coactivator activity
Processes
androgen receptor signaling pathway / cellular response to estradiol stimulus / chromatin organization / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / DNA repair / double-strand break repair / double-strand break repair via homologous recombination / double-strand break repair via nonhomologous end joining / double-strand break repair via synthesis-dependent strand annealing / histone acetylation / negative regulation of interleukin-2 production / negative regulation of transcription from RNA polymerase II promoter / negative regulation of transcription, DNA-templated / positive regulation of protein acetylation / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of growth / response to ionizing radiation / transcription, DNA-templated / viral process
Components
NuA4 histone acetyltransferase complex / nucleolus / nucleoplasm / nucleus / perinuclear region of cytoplasm / Piccolo NuA4 histone acetyltransferase complex / Swr1 complex / transcription factor complex
General Function
Transcription coactivator activity
Specific Function
Catalytic subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Directly acetylates and activates ATM. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome. In case of HIV-1 infection, interaction with the viral Tat protein leads to KAT5 polyubiquitination and targets it to degradation. Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2. Promotes FOXP3 acetylation and positively regulates its transcriptional repressor activity (PubMed:17360565).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021710|Histone acetyltransferase KAT5 (KAT5)
ATGGCGGAGGTGGTGAGTCCGGTGCCCGGGGCGGGGCGGAGGGAGCCAGGGGAGGTGGGT
AGAGCCCGAGGCCCCCCAGTAGCCGACCCTGGCGTCGCGCTGTCTCCCCAGGGGGAGATA
ATCGAGGGCTGCCGCCTACCCGTGCTGCGGCGGAACCAGGACAACGAAGATGAGTGGCCC
CTGGCCGAGATCCTGAGCGTGAAGGACATCAGTGGCCGGAAGCTTTTCTACGTCCATTAC
ATTGACTTCAACAAACGTCTGGATGAATGGGTGACGCATGAGCGGCTGGACCTAAAGAAG
ATCCAGTTCCCCAAGAAAGAGGCCAAGACCCCCACTAAGAACGGACTTCCTGGGTCCCGT
CCTGGCTCTCCAGAGAGAGAGGTGAAACGGAAGGTGGAGGTGGTTTCACCAGCAACTCCA
GTGCCCAGCGAGACAGCCCCGGCCTCGGTTTTTCCCCAGAATGGAGCCGCCCGTAGGGCA
GTGGCAGCCCAGCCAGGACGGAAGCGAAAATCGAATTGTTTGGGCACTGATGAGGACTCC
CAGGACAGCTCTGATGGAATACCGTCAGCACCACGCATGACTGGCAGCCTGGTGTCTGAT
CGAAGCCACGACGACATCGTCACCCGGATGAAGAACATTGAGTGCATTGAGCTGGGCCGG
CACCGCCTCAAGCCGTGGTACTTCTCCCCGTACCCACAGGAACTCACCACATTGCCTGTC
CTCTACCTGTGCGAGTTCTGCCTCAAGTACGGCCGTAGTCTCAAGTGTCTTCAGCGTCAT
TTGACCAAGTGTGACCTACGACATCCTCCAGGCAATGAGATTTACCGCAAGGGCACCATC
TCCTTCTTTGAGATTGATGGACGTAAGAACAAGAGTTATTCCCAGAACCTGTGTCTTTTG
GCCAAGTGTTTCCTTGACCATAAGACACTGTACTATGACACAGACCCTTTCCTCTTCTAC
GTCATGACAGAGTATGACTGTAAGGGCTTCCACATCGTGGGCTACTTCTCCAAGGAGAAA
GAATCAACGGAAGACTACAATGTGGCCTGCATCCTAACCCTGCCTCCCTACCAGCGCCGG
GGCTACGGCAAGCTGCTGATCGAGTTCAGCTATGAACTCTCCAAAGTGGAAGGGAAAACA
GGGACCCCTGAGAAGCCCCTCTCAGACCTTGGCCTCCTATCCTATCGAAGCTACTGGTCC
CAGACCATCCTGGAGATCCTGATGGGGCTGAAGTCGGAGAGCGGGGAGAGGCCACAGATC
ACCATCAATGAGATTAGTGAAATCACCAGCATCAAGAAGGAGGATGTCATCTCCACTCTG
CAGTACCTCAATCTCATCAACTACTACAAGGGCCAGTACATCCTCACACTGTCAGAGGAC
ATCGTGGATGGCCATGAGCGGGCCATGCTCAAGCGGCTCCTGCGGATCGACTCCAAGTGT
CTGCACTTCACTCCCAAGGACTGGAGCAAGAGGGGGAAGTGGTGA
Chromosome Location
11
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ92993
UniProtKB Entry NameKAT5_HUMAN
HGNC IDHGNC:5275
General References
  1. Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G: Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology. 1996 Feb 15;216(2):357-66. [Article]
  2. Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV: PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production. Mol Cell Biol. 2001 Jul;21(14):4470-81. [Article]
  3. Legube G, Trouche D: Identification of a larger form of the histone acetyl transferase Tip60. Gene. 2003 May 22;310:161-8. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Cai Y, Jin J, Tomomori-Sato C, Sato S, Sorokina I, Parmely TJ, Conaway RC, Conaway JW: Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. J Biol Chem. 2003 Oct 31;278(44):42733-6. Epub 2003 Sep 8. [Article]
  8. Kimura A, Horikoshi M: Tip60 acetylates six lysines of a specific class in core histones in vitro. Genes Cells. 1998 Dec;3(12):789-800. [Article]
  9. Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y: Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell. 2000 Aug 18;102(4):463-73. [Article]
  10. Lee HJ, Chun M, Kandror KV: Tip60 and HDAC7 interact with the endothelin receptor a and may be involved in downstream signaling. J Biol Chem. 2001 May 18;276(20):16597-600. Epub 2001 Mar 21. [Article]
  11. Legube G, Linares LK, Lemercier C, Scheffner M, Khochbin S, Trouche D: Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation. EMBO J. 2002 Apr 2;21(7):1704-12. [Article]
  12. Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B: MYC recruits the TIP60 histone acetyltransferase complex to chromatin. EMBO Rep. 2003 Jun;4(6):575-80. [Article]
  13. Lemercier C, Legube G, Caron C, Louwagie M, Garin J, Trouche D, Khochbin S: Tip60 acetyltransferase activity is controlled by phosphorylation. J Biol Chem. 2003 Feb 14;278(7):4713-8. Epub 2002 Dec 4. [Article]
  14. Xiao H, Chung J, Kao HY, Yang YC: Tip60 is a co-repressor for STAT3. J Biol Chem. 2003 Mar 28;278(13):11197-204. Epub 2003 Jan 27. [Article]
  15. Doyon Y, Cote J: The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev. 2004 Apr;14(2):147-54. [Article]
  16. Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M, Trouche D: Role of the histone acetyl transferase Tip60 in the p53 pathway. J Biol Chem. 2004 Oct 22;279(43):44825-33. Epub 2004 Aug 13. [Article]
  17. Panchenko MV, Zhou MI, Cohen HT: von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity. J Biol Chem. 2004 Dec 31;279(53):56032-41. Epub 2004 Oct 22. [Article]
  18. Doyon Y, Selleck W, Lane WS, Tan S, Cote J: Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. [Article]
  19. Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM, Livingston DM, Amati B: E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1. Mol Cell Biol. 2004 May;24(10):4546-56. [Article]
  20. Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL, Bernards R: A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature. 2004 Mar 25;428(6981):431-7. [Article]
  21. Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y, Yoshida M, Benkirane M, Trouche D, Khochbin S: HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses. EMBO J. 2005 Jul 20;24(14):2634-45. Epub 2005 Jul 7. [Article]
  22. Sun Y, Jiang X, Chen S, Fernandes N, Price BD: A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13182-7. Epub 2005 Sep 2. [Article]
  23. Weiske J, Huber O: The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem. 2006 Sep 15;281(37):27356-66. Epub 2006 Jul 11. [Article]
  24. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. [Article]
  25. Li B, Samanta A, Song X, Iacono KT, Bembas K, Tao R, Basu S, Riley JL, Hancock WW, Shen Y, Saouaf SJ, Greene MI: FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4571-6. Epub 2007 Mar 7. [Article]
  26. Wang J, Liu N, Liu Z, Li Y, Song C, Yuan H, Li YY, Zhao X, Lu H: The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to regulate apolipoprotein CIII promoter. Biochim Biophys Acta. 2008 Feb;1783(2):224-36. Epub 2007 Oct 4. [Article]
  27. Miyajima N, Maruyama S, Bohgaki M, Kano S, Shigemura M, Shinohara N, Nonomura K, Hatakeyama S: TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells. Cancer Res. 2008 May 1;68(9):3486-94. doi: 10.1158/0008-5472.CAN-07-6059. [Article]
  28. Bhoumik A, Singha N, O'Connell MJ, Ronai ZA: Regulation of TIP60 by ATF2 modulates ATM activation. J Biol Chem. 2008 Jun 20;283(25):17605-14. doi: 10.1074/jbc.M802030200. Epub 2008 Apr 8. [Article]
  29. Cheng Z, Ke Y, Ding X, Wang F, Wang H, Wang W, Ahmed K, Liu Z, Xu Y, Aikhionbare F, Yan H, Liu J, Xue Y, Yu J, Powell M, Liang S, Wu Q, Reddy SE, Hu R, Huang H, Jin C, Yao X: Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response. Oncogene. 2008 Feb 7;27(7):931-41. Epub 2007 Aug 20. [Article]
  30. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  31. Kikuchi M, Okumura F, Tsukiyama T, Watanabe M, Miyajima N, Tanaka J, Imamura M, Hatakeyama S: TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells. Biochim Biophys Acta. 2009 Dec;1793(12):1828-36. doi: 10.1016/j.bbamcr.2009.11.001. Epub 2009 Nov 10. [Article]
  32. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  33. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  34. Jeon BN, Kim MK, Yoon JH, Kim MY, An H, Noh HJ, Choi WI, Koh DI, Hur MW: Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress. Nucleic Acids Res. 2014 Oct;42(18):11447-61. doi: 10.1093/nar/gku857. Epub 2014 Sep 22. [Article]
  35. Obri A, Ouararhni K, Papin C, Diebold ML, Padmanabhan K, Marek M, Stoll I, Roy L, Reilly PT, Mak TW, Dimitrov S, Romier C, Hamiche A: ANP32E is a histone chaperone that removes H2A.Z from chromatin. Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01992Coenzyme Ainvestigational, nutraceuticalunknownDetails
DB02039S-Acetyl-CysteineexperimentalunknownDetails