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Q8CHK4

- KAT5_MOUSE

UniProt

Q8CHK4 - KAT5_MOUSE

Protein

Histone acetyltransferase KAT5

Gene

Kat5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 2 (28 Nov 2003)
      Previous versions | rss
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    Functioni

    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. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Directly acetylates and activates ATM. Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome By similarity.By similarity

    Catalytic activityi

    Acetyl-CoA + [histone] = CoA + acetyl-[histone].

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei327 – 3271By similarity
    Active sitei369 – 3691NucleophileBy similarity
    Binding sitei372 – 3721Acetyl-CoABy similarity
    Binding sitei407 – 4071Acetyl-CoABy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri261 – 28323C2HC-typeAdd
    BLAST

    GO - Molecular functioni

    1. histone acetyltransferase activity Source: UniProtKB-EC
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. transcription coactivator activity Source: UniProtKB

    GO - Biological processi

    1. DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
    2. double-strand break repair Source: Ensembl
    3. negative regulation of interleukin-2 production Source: Ensembl
    4. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    5. positive regulation of transcription, DNA-templated Source: UniProtKB
    6. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    7. proteasome-mediated ubiquitin-dependent protein catabolic process Source: Ensembl
    8. regulation of growth Source: UniProtKB-KW
    9. regulation of transcription, DNA-templated Source: MGI
    10. response to ionizing radiation Source: Ensembl
    11. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Acyltransferase, Chromatin regulator, Transferase

    Keywords - Biological processi

    Growth regulation, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_216539. formation of the beta-catenin:TCF transactivating complex.
    REACT_226917. HATs acetylate histones.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histone acetyltransferase KAT5 (EC:2.3.1.48)
    Alternative name(s):
    60 kDa Tat-interactive protein
    Short name:
    Tip60
    Histone acetyltransferase HTATIP
    Lysine acetyltransferase 5
    Gene namesi
    Name:Kat5
    Synonyms:Htatip, Tip60
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 19

    Organism-specific databases

    MGIiMGI:1932051. Kat5.

    Subcellular locationi

    Nucleus By similarity. Nucleusnucleolus 1 Publication. Cytoplasmperinuclear region By similarity
    Note: Upon stimulation with EDN1, it is exported from the nucleus to the perinuclear region.By similarity

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. NuA4 histone acetyltransferase complex Source: UniProtKB
    3. nucleolus Source: UniProtKB
    4. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    5. Piccolo NuA4 histone acetyltransferase complex Source: UniProtKB
    6. Swr1 complex Source: UniProtKB
    7. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 513513Histone acetyltransferase KAT5PRO_0000051581Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei52 – 521N6-acetyllysineBy similarity
    Modified residuei86 – 861PhosphoserineBy similarity
    Modified residuei90 – 901Phosphoserine; by CDK1By similarity
    Modified residuei327 – 3271N6-acetyllysine; by autocatalysisBy similarity
    Cross-linki430 – 430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Cross-linki451 – 451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Post-translational modificationi

    Sumoylated by UBE2I at Lys-430 and Lys-451, leading to increase of its histone acetyltransferase activity in UV-induced DNA damage response, as well as its translocation to nuclear bodies.By similarity
    Phosphorylated on Ser-86 and Ser-90; enhanced during G2/M phase. Phosphorylated form has a higher activity By similarity.By similarity
    Ubiquitinated by MDM2, leading to its proteasome-dependent degradation.By similarity
    Autoacetylation at Lys-327 is required for proper function.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ8CHK4.
    PaxDbiQ8CHK4.
    PRIDEiQ8CHK4.

    PTM databases

    PhosphoSiteiQ8CHK4.

    Expressioni

    Tissue specificityi

    Expressed in testis, heart, brain, kidney and liver. Weakly expressed in lung.1 Publication

    Gene expression databases

    BgeeiQ8CHK4.
    GenevestigatoriQ8CHK4.

    Interactioni

    Subunit structurei

    Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6 By similarity. HTATTIP/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4 By similarity. The NuA4 complex interacts with MYC By similarity. Interacts with ATM By similarity. Interacts with JADE1 By similarity. Interacts with PLA2G4A/CPLA2, EDNRA and HDAC7 By similarity. Interacts with the cytoplasmic tail of APP and APBB1/FE65 By similarity. Interacts with TRIM24 and TRIM68 By similarity. Forms a complex with SENP6 and UBE2I in response to UV irradiation. Identified in a complex with HINT1 By similarity. Interacts with ATF2 and CUL3. Interacts with NR1D2 (via N-terminus). Component of a SWR1-like complex By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Atxn1P542542EBI-1169948,EBI-1169713

    Protein-protein interaction databases

    BioGridi219884. 11 interactions.
    IntActiQ8CHK4. 24 interactions.
    MINTiMINT-4302182.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CHK4.
    SMRiQ8CHK4. Positions 11-79, 230-504.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini227 – 504278MYST-type HATAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni368 – 513146Interaction with ATF2By similarityAdd
    BLAST
    Regioni377 – 3837Acetyl-CoA bindingBy similarity

    Sequence similaritiesi

    Belongs to the MYST (SAS/MOZ) family.Curated
    Contains 1 C2HC-type zinc finger.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri261 – 28323C2HC-typeAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5027.
    GeneTreeiENSGT00550000074503.
    HOGENOMiHOG000182457.
    KOiK11304.
    OMAiHDDIITR.
    OrthoDBiEOG7ZKS9R.
    PhylomeDBiQ8CHK4.
    TreeFamiTF317619.

    Family and domain databases

    Gene3Di3.40.630.30. 1 hit.
    InterProiIPR016181. Acyl_CoA_acyltransferase.
    IPR000953. Chromo_domain/shadow.
    IPR016197. Chromodomain-like.
    IPR002717. MOZ_SAS.
    IPR025995. Tudor-knot.
    [Graphical view]
    PfamiPF01853. MOZ_SAS. 1 hit.
    PF11717. Tudor-knot. 1 hit.
    [Graphical view]
    SMARTiSM00298. CHROMO. 1 hit.
    [Graphical view]
    SUPFAMiSSF54160. SSF54160. 1 hit.
    SSF55729. SSF55729. 1 hit.
    PROSITEiPS51726. MYST_HAT. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8CHK4-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAEVGEIIEG CRLPVLRRNQ DNEDEWPLAE ILSVKDISGR KLFYVHYIDF    50
    NKRLDEWVTH ERLDLKKIQF PKKEAKTPTK NGLPGSRPGS PEREVPASAQ 100
    ASGKTLPIPV QITLRFNLPK EREAIPGGEP DQPLSSSSCL QPNHRSTKRK 150
    VEVVSPATPV PSETAPASVF PQNGSARRAV AAQPGRKRKS NCLGTDEDSQ 200
    DSSDGIPSAP RMTGSLVSDR SHDDIVTRMK NIECIELGRH RLKPWYFSPY 250
    PQELTTLPVL YLCEFCLKYG RSLKCLQRHL TKCDLRHPPG NEIYRKGTIS 300
    FFEIDGRKNK SYSQNLCLLA KCFLDHKTLY YDTDPFLFYV MTEYDCKGFH 350
    IVGYFSKEKE STEDYNVACI LTLPPYQRRG YGKLLIEFSY ELSKVEGKTG 400
    TPEKPLSDLG LLSYRSYWSQ TILEILMGLK SESGERPQIT INEISEITSI 450
    KKEDVISTLQ YLNLINYYKG QYILTLSEDI VDGHERAMLK RLLRIDSKCL 500
    HFTPKDWSKR GKW 513
    Length:513
    Mass (Da):58,598
    Last modified:November 28, 2003 - v2
    Checksum:iEACEE4D544C0DB60
    GO
    Isoform 2 (identifier: Q8CHK4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         96-147: Missing.

    Show »
    Length:461
    Mass (Da):53,093
    Checksum:iD3B238AF01737EF3
    GO
    Isoform 3 (identifier: Q8CHK4-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         4-4: V → VVSPVPGAGRREPGEVGRARGPPVADPGVALSPQ

    Show »
    Length:546
    Mass (Da):61,814
    Checksum:i8557B105D8F4B291
    GO
    Isoform 4 (identifier: Q8CHK4-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-211: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:302
    Mass (Da):35,396
    Checksum:iD96A7FCCB49FA85D
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 211211Missing in isoform 4. 1 PublicationVSP_009105Add
    BLAST
    Alternative sequencei4 – 41V → VVSPVPGAGRREPGEVGRAR GPPVADPGVALSPQ in isoform 3. CuratedVSP_009106
    Alternative sequencei96 – 14752Missing in isoform 2. 2 PublicationsVSP_009107Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY061983 Genomic DNA. Translation: AAL34981.1.
    AF528194 mRNA. Translation: AAN77140.1.
    AF528195 mRNA. Translation: AAN77141.1.
    AF528196 mRNA. Translation: AAN77142.1.
    AB055409 mRNA. Translation: BAC53807.1.
    BC129968 mRNA. Translation: AAI29969.1.
    CCDSiCCDS29472.1. [Q8CHK4-1]
    RefSeqiNP_001186176.1. NM_001199247.1. [Q8CHK4-2]
    NP_001186177.1. NM_001199248.1.
    NP_848752.1. NM_178637.2. [Q8CHK4-1]
    UniGeneiMm.228930.

    Genome annotation databases

    EnsembliENSMUST00000113641; ENSMUSP00000109271; ENSMUSG00000024926. [Q8CHK4-1]
    GeneIDi81601.
    KEGGimmu:81601.
    UCSCiuc008gdy.2. mouse. [Q8CHK4-1]
    uc008geb.2. mouse. [Q8CHK4-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY061983 Genomic DNA. Translation: AAL34981.1 .
    AF528194 mRNA. Translation: AAN77140.1 .
    AF528195 mRNA. Translation: AAN77141.1 .
    AF528196 mRNA. Translation: AAN77142.1 .
    AB055409 mRNA. Translation: BAC53807.1 .
    BC129968 mRNA. Translation: AAI29969.1 .
    CCDSi CCDS29472.1. [Q8CHK4-1 ]
    RefSeqi NP_001186176.1. NM_001199247.1. [Q8CHK4-2 ]
    NP_001186177.1. NM_001199248.1.
    NP_848752.1. NM_178637.2. [Q8CHK4-1 ]
    UniGenei Mm.228930.

    3D structure databases

    ProteinModelPortali Q8CHK4.
    SMRi Q8CHK4. Positions 11-79, 230-504.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 219884. 11 interactions.
    IntActi Q8CHK4. 24 interactions.
    MINTi MINT-4302182.

    PTM databases

    PhosphoSitei Q8CHK4.

    Proteomic databases

    MaxQBi Q8CHK4.
    PaxDbi Q8CHK4.
    PRIDEi Q8CHK4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000113641 ; ENSMUSP00000109271 ; ENSMUSG00000024926 . [Q8CHK4-1 ]
    GeneIDi 81601.
    KEGGi mmu:81601.
    UCSCi uc008gdy.2. mouse. [Q8CHK4-1 ]
    uc008geb.2. mouse. [Q8CHK4-2 ]

    Organism-specific databases

    CTDi 10524.
    MGIi MGI:1932051. Kat5.

    Phylogenomic databases

    eggNOGi COG5027.
    GeneTreei ENSGT00550000074503.
    HOGENOMi HOG000182457.
    KOi K11304.
    OMAi HDDIITR.
    OrthoDBi EOG7ZKS9R.
    PhylomeDBi Q8CHK4.
    TreeFami TF317619.

    Enzyme and pathway databases

    Reactomei REACT_216539. formation of the beta-catenin:TCF transactivating complex.
    REACT_226917. HATs acetylate histones.

    Miscellaneous databases

    ChiTaRSi KAT5. mouse.
    NextBioi 350414.
    PROi Q8CHK4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8CHK4.
    Genevestigatori Q8CHK4.

    Family and domain databases

    Gene3Di 3.40.630.30. 1 hit.
    InterProi IPR016181. Acyl_CoA_acyltransferase.
    IPR000953. Chromo_domain/shadow.
    IPR016197. Chromodomain-like.
    IPR002717. MOZ_SAS.
    IPR025995. Tudor-knot.
    [Graphical view ]
    Pfami PF01853. MOZ_SAS. 1 hit.
    PF11717. Tudor-knot. 1 hit.
    [Graphical view ]
    SMARTi SM00298. CHROMO. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54160. SSF54160. 1 hit.
    SSF55729. SSF55729. 1 hit.
    PROSITEi PS51726. MYST_HAT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization and expression of the mouse tat interactive protein 60 kD (TIP60) gene."
      McAllister D., Merlo X., Lough J.W.
      Gene 289:169-176(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Strain: 129/SvJ.
    2. "Identification of a larger form of the histone acetyl transferase Tip60."
      Legube G., Trouche D.
      Gene 310:161-168(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 3).
    3. "Cloning of mouse Tip60."
      Szendro P.I., Cadenas C., Eichele G.
      Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Strain: C57BL/6.
    4. "Isolation and characterization of novel human and mouse genes, which are expressed in the digestive tract."
      Daigo Y., Takayama I., Fujino M.A.
      Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
      Strain: W/Wv.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).

    Entry informationi

    Entry nameiKAT5_MOUSE
    AccessioniPrimary (citable) accession number: Q8CHK4
    Secondary accession number(s): A1L394
    , Q8CGZ3, Q8CGZ4, Q8VIH0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2003
    Last sequence update: November 28, 2003
    Last modified: October 1, 2014
    This is version 113 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3