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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)

Identity

Other aliasHTATIP (HIV-1 Tat interacting protein, 60kDa)
Tip60
Tip
60kDa Tat interacting protein
HIV-1 Tat interacting protein
cPLA(2) interacting protein
iTip60
PLIP/Tip60b
Tip60a
Esa1
Hs.6364
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)

DNA/RNA

 
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.

    Protein

     
    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
    Predicted:
  • P.troglodytes: HTATIP
  • M.mulatta: HTATIP
  • Mutations

    Note No mutation in Tip60 protein has been currently described.

    Implicated in

    Note
      
    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.
      

    Bibliography

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    Tip60 is a nuclear hormone receptor coactivator.
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    PMID 10364196
     
    Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response.
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    HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses.
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    PMID 11591700
     
    Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor.
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    PMID 11994312
     
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    PMID 12717424
     
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    Hobbs CA, Wei G, DeFeo K, Paul B, Hayes CS, Gilmour SK
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    PMID 16912189
     
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    Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator.
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    PMID 8607265
     
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    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
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    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
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    PMID 15310756
     
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    Tip60 acetyltransferase activity is controlled by phosphorylation.
    Lemercier C, Legube G, Caron C, Louwagie M, Garin J, Trouche D, Khochbin S
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    PMID 12036595
     
    Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks.
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    PMID 11111051
     
    RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.
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    PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production.
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    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
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    PMID 16141325
     
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    PMID 17189186
     
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    Citation

    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 : http://AtlasGeneticsOncology.org/Genes/HTATIPID40893ch11q13.html


    External links

    Nomenclature
    Cards
    AtlasHTATIPID40893ch11q13.txt
    Aliases
    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
    Miscellaneous
    canSAR (ICR) (select the gene name)
    Probes
    Litterature
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed


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    indexed on : Thu Oct 18 17:39:12 CEST 2018

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