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KAT5 (HIV-1 Tat interacting protein, 60kDa)

Written2007-10Lise Mattera
Dr Trouche Team, LBCMCP, UMR 5088 CNRS, 118 route de Narbonne, 31062 Toulouse cedex 9, France

(Note : for Links provided by Atlas : click)


Other aliasHTATIP (HIV-1 Tat interacting protein, 60kDa)
60kDa Tat interacting protein
HIV-1 Tat interacting protein
cPLA(2) interacting protein
LocusID (NCBI) 10524
Atlas_Id 40893
Location 11q13.1  [Link to chromosome band 11q13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
KAT5 (11q13.1) / KAT5 (11q13.1)KAT5 (11q13.1) / RASIP1 (19q13.33)


Description The HTATIP gene consists of 14 exons. 7,586 bases.
Transcription The predominant mRNA transcribed from this gene is 2,229 bp long. This is actually the isoform 2 of HTATIP.
Two others isoforms generated by alternative splicing have been described:
  • Isoform 1 retains the alternatively spliced intron 1.
  • Isoform 3 lacks exon 5.
  • Pseudogene No pseudogene is currently known.


    Description The Tip60 protein (isoform 2) is 513 amino acids long and its molecular weight is about 60 kDa. It was cloned and characterized in 1996 thanks to its interaction with the HIV-1 transactivator Tat protein.
    Isoform 1 produces a 546 amino acids long protein.
    Isoform 3 produces a 461 amino acids long protein.
    A novel isoform, Tip55, encodes a novel splicing variant corresponding to 103 amino acids of the C-terminus.
    The domain architectures of human TIP60 is similar to yeast Esa1 protein and consist of a chromodomain and a MYST domain harboring a zinc finger and an Acetyl-CoA binding site.
    Expression Tip60 is ubiquitously expressed.
    In mouse adult tissues Tip60 is expressed in the following decreasing order of intensity: testis, heart, brain, kidney, liver, lung, with little to no expression in spleen and skeletal muscle .
    In human, Tip60 (Isoform 2) and PLIP (Isoform 3) are expressed in human heart, kidney and brain tissue.
    With a half-life of approximately 30 minutes, Tip60 is very unstable. In normal conditions, the proteasome pathway permits to maintain low protein levels. Tip60 is ubiquitinated and targeted to proteasome-mediated degradation by Mdm2 but also by p300-associated E4 ubiquitin ligase. Tip60 is stabilized after DNA damage, and accumulates in cells. Moreover, Tip60 is the target of several post-translational modifications such as phosphorylation on serine 86 and 90 by cdc2 but also acetylation by p300/CBP acetyltransferases. Acetylation by p300/CBP occurs in the zinc finger of Tip60 but consequences of this modification are currently not known. Finally, a recent report shows that Tip60 is sumoylated at lysines 430 and 451 via Ubc9.
    No data are available about regulation of the Tip60 promoter.
    Localisation Tip60 (Isoform 2) is nuclear. PLIP (Isoform 3) is nuclear but also cytoplasmic.
    Function Tip60 is a Histone Acetyltransferase (HAT), which belongs to the MYST family. It participates in a multimolecular complex: The Tip60 complex, which contains proteins such as p400, Tip49a and Tip49b . Within this complex, Tip60 exerts its HAT activity on nucleosomal histone H4. Tip60 is involved in various cellular mechanisms:
  • In transcription: Tip60 acts as a coactivator. Indeed, Tip60 is able to interact with transcription factors, such as E2F-1 or c-Myc. Tip60 can be recruited to Myc and E2F-1 target promoters and enhances Myc transactivation. It also acetylates histone H4 on several E2F responsive genes. Moreover Tip60 was found to be involved in nuclear receptor (NR) signaling and to be a NR-coregulator.
  • In apoptosis and cell cycle arrest: Tip60 can interact with and acetylate the tumor suppressor p53. It enhances p53 binding to pro-apoptotic target genes like PUMA, Bax or Fas. Moreover, Tip60 is also required for cell growth arrest via the p21-dependent pathway.
  • In DNA repair: Tip60 is involved in double strand breaks (DSB) repair. Interacting and acetylating ATM, Tip60 participates in DNA damage signaling. But, Tip60 is also involved directly in DSB repair since it is recruited, with TRRAP, to the DSB site. Tip60 interacts with the chromatin surrounding sites of DSBs and this recruitment is responsible for hyperacetylation of histone H4.
  • Homology Tip60 CHROMO domain has been identified by sequence homology with the Heterochromatin-associated protein 1 (HP1) chromodomain, which recognizes methylated lysines. It also harbors the MYST domain, which is highly conserved from yeast to human.
    Homologs in other species:
  • S. Cerevisae: Esa1
  • D. Melanogaster: DmeI/Tip60
  • M. musculus: Htatip
  • R. norvegicus: Htatip
  • P.troglodytes: HTATIP
  • M.mulatta: HTATIP
  • Mutations

    Note No mutation in Tip60 protein has been currently described.

    Implicated in

    Entity Acquired Immunodeficiency Syndrome (AIDS)
    Disease Tip60 interacts with the HIV-1 transactivator Tat and this interaction inhibits Tip60 HAT activity. Moreover, in Jurkat cells, Tat enhances Tip60 turnover since it uses the p300/CBP-associated E4-type ubiquitin-ligase activity to induce polyubiquitynation and degradation of Tip60. This targeting by Tat induces an impairment of Tip60-dependent apoptosis after DNA damage.
    Entity Neurodegenerative diseases
    Entity Alzheimer' disease
    Disease In the nucleus of human H4 neuroglioma cells, TIP60 can interact with a free carboxyl-terminal intracellular fragment, APP-CT, which is generated by the cleavage of the Amyloid precursor protein APP by a gamma-secretase. This fragment induces apoptosis of neuroglioma and this cell death is enhanced when a wild type form of Tip60 is transfected. Thus Tip60 might play a role in Alzheimer's disease neurodegeneration.
    Entity Spinocerebellar ataxia type-1
    Disease TIP60 participates in a complex with ATXN1 and ROR-alpha in a conditional transgenic mouse model of Spinocerebellar ataxia type-1 (SCA1), one of the nine inherited polyglutamine neurodegenerative diseases.
    Entity Cancers
    Entity Prostate cancer
    Disease Immunohistochemistry experiments have shown that Tip60 accumulates in the nucleus of hormone-refractory prostate cancer compared to prostate hyperplasia and primary prostate cancer.
    Entity Lung cancer and colon cancer
    Disease Real time RT-PCR experiments have shown that Tip60 mRNA is under expressed in colon and lung carcinomas.
    Entity Skin cancer
    Disease The expression levels of TIP60 protein, analyzed by western blot, were found to be greater in skin tumors as compared to adjacent non-tumor-bearing skin in a skin cancer mouse model (K6/ODC mouse). Additionally, the interaction between Tip60 and E2F1 is enhanced in these tumors.
    Entity HTLV-1 induced leukemogenesis
    Disease Enhancement of c-Myc transforming activity by HTLV-1 p30II oncoprotein in HeLa cells requires TIP60 HAT activity.


    A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions.
    Awasthi S, Sharma A, Wong K, Zhang J, Matlock EF, Rogers L, Motloch P, Takemoto S, Taguchi H, Cole MD, Lüscher B, Dittrich O, Tagami H, Nakatani Y, McGee M, Girard AM, Gaughan L, Robson CN, Monnat RJ Jr, Harrod R
    Molecular and cellular biology. 2005 ; 25 (14) : 6178-6198.
    PMID 15988028
    A large-scale RNAi screen in human cells identifies new components of the p53 pathway.
    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
    Nature. 2004 ; 428 (6981) : 431-437.
    PMID 15042092
    Tip60 is a nuclear hormone receptor coactivator.
    Brady ME, Ozanne DM, Gaughan L, Waite I, Cook S, Neal DE, Robson CN
    The Journal of biological chemistry. 1999 ; 274 (25) : 17599-17604.
    PMID 10364196
    Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response.
    Cheng Z, Ke Y, Ding X, Wang F, Wang H, Ahmed K, Liu Z, Xu Y, Aikhionbare F, Yan H, Liu J, Xue Y, Powell M, Liang S, Reddy SE, Hu R, Huang H, Jin C, Yao X
    Oncogene. 2008 ; 27 (7) : 931-941.
    PMID 17704809
    HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses.
    Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y, Yoshida M, Benkirane M, Trouche D, Khochbin S
    The EMBO journal. 2005 ; 24 (14) : 2634-2645.
    PMID 16001085
    Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat.
    Creaven M, Hans F, Mutskov V, Col E, Caron C, Dimitrov S, Khochbin S
    Biochemistry. 1999 ; 38 (27) : 8826-8830.
    PMID 10393559
    MYC recruits the TIP60 histone acetyltransferase complex to chromatin.
    Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B
    EMBO reports. 2003 ; 4 (6) : 575-580.
    PMID 12776177
    Tip60 is a co-activator specific for class I nuclear hormone receptors.
    Gaughan L, Brady ME, Cook S, Neal DE, Robson CN
    The Journal of biological chemistry. 2001 ; 276 (50) : 46841-46848.
    PMID 11591700
    Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor.
    Gaughan L, Logan IR, Cook S, Neal DE, Robson CN
    The Journal of biological chemistry. 2002 ; 277 (29) : 25904-25913.
    PMID 11994312
    Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development.
    Halkidou K, Gnanapragasam VJ, Mehta PB, Logan IR, Brady ME, Cook S, Leung HY, Neal DE, Robson CN
    Oncogene. 2003 ; 22 (16) : 2466-2477.
    PMID 12717424
    Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase.
    Hobbs CA, Wei G, DeFeo K, Paul B, Hayes CS, Gilmour SK
    Cancer research. 2006 ; 66 (16) : 8116-8122.
    PMID 16912189
    Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.
    Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y
    Cell. 2000 ; 102 (4) : 463-473.
    PMID 10966108
    Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator.
    Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G
    Virology. 1996 ; 216 (2) : 357-366.
    PMID 8607265
    Co-activation of atrial natriuretic factor promoter by Tip60 and serum response factor.
    Kim MS, Merlo X, Wilson C, Lough J
    The Journal of biological chemistry. 2006 ; 281 (22) : 15082-15089.
    PMID 16597624
    The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells.
    Kinoshita A, Whelan CM, Berezovska O, Hyman BT
    The Journal of biological chemistry. 2002 ; 277 (32) : 28530-28536.
    PMID 12032152
    New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas.
    LLeonart ME, Vidal F, Gallardo D, Diaz-Fuertes M, Rojo F, Cuatrecasas M, López-Vicente L, Kondoh H, Blanco C, Carnero A, Ramón y Cajal S
    Oncology reports. 2006 ; 16 (3) : 603-608.
    PMID 16865262
    Role of the histone acetyl transferase Tip60 in the p53 pathway.
    Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M, Trouche D
    The Journal of biological chemistry. 2004 ; 279 (43) : 44825-44833.
    PMID 15310756
    Identification of a larger form of the histone acetyl transferase Tip60.
    Legube G, Trouche D
    Gene. 2003 ; 310 : 161-168.
    PMID 12801643
    Tip60 acetyltransferase activity is controlled by phosphorylation.
    Lemercier C, Legube G, Caron C, Louwagie M, Garin J, Trouche D, Khochbin S
    The Journal of biological chemistry. 2003 ; 278 (7) : 4713-4718.
    PMID 12468530
    Characterization and expression of the mouse tat interactive protein 60 kD (TIP60) gene.
    McAllister D, Merlo X, Lough J
    Gene. 2002 ; 289 (1-2) : 169-176.
    PMID 12036595
    Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks.
    Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, Herceg Z
    Nature cell biology. 2006 ; 8 (1) : 91-99.
    PMID 16341205
    Identification of an alternatively spliced form of the Tat interactive protein (Tip60), Tip60(beta).
    Ran Q, Pereira-Smith OM
    Gene. 2000 ; 258 (1-2) : 141-146.
    PMID 11111051
    RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.
    Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT
    Cell. 2006 ; 127 (4) : 697-708.
    PMID 17110330
    PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production.
    Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV
    Molecular and cellular biology. 2001 ; 21 (14) : 4470-4481.
    PMID 11416127
    A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM.
    Sun Y, Jiang X, Chen S, Fernandes N, Price BD
    Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (37) : 13182-13187.
    PMID 16141325
    Acetylation of the p53 DNA-binding domain regulates apoptosis induction.
    Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS, McMahon SB
    Molecular cell. 2006 ; 24 (6) : 841-851.
    PMID 17189187
    Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis.
    Tang Y, Luo J, Zhang W, Gu W
    Molecular cell. 2006 ; 24 (6) : 827-839.
    PMID 17189186
    E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1.
    Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM, Livingston DM, Amati B
    Molecular and cellular biology. 2004 ; 24 (10) : 4546-4556.
    PMID 15121871
    Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression.
    Tyteca S, Vandromme M, Legube G, Chevillard-Briet M, Trouche D
    The EMBO journal. 2006 ; 25 (8) : 1680-1689.
    PMID 16601686


    This paper should be referenced as such :
    Mattera, L
    HTATIP (HIV-1 Tat interacting protein, 60kDa)
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):213-216.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    External links

    Genomic and cartography
    Gene and transcription
    RefSeq transcript (Entrez)
    RefSeq genomic (Entrez)
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)10524
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Protein Interaction databases
    Ontologies - Pathways
    Clinical trials, drugs, therapy
    canSAR (ICR) (select the gene name)
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    indexed on : Thu Oct 18 17:39:12 CEST 2018

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