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Q8CHK4

- KAT5_MOUSE

UniProt

Q8CHK4 - KAT5_MOUSE

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Protein

Histone acetyltransferase KAT5

Gene

Kat5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei403 – 4031Proton donor/acceptorBy similarity
Binding sitei407 – 4071Acetyl-CoABy similarity
Binding sitei416 – 4161Acetyl-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. transcription coactivator activity Source: UniProtKB

GO - Biological processi

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

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:2.3.1.48By similarity)
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. Piccolo NuA4 histone acetyltransferase complex Source: UniProtKB
  5. Swr1 complex Source: UniProtKB
  6. transcription factor complex Source: MGI
Complete GO annotation...

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. The phosphorylated form has a higher HAT activity.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.
ExpressionAtlasiQ8CHK4. baseline and differential.
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
Regioni370 – 3723Acetyl-CoA bindingBy similarity
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.
InParanoidiQ8CHK4.
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

        10         20         30         40         50
MAEVGEIIEG CRLPVLRRNQ DNEDEWPLAE ILSVKDISGR KLFYVHYIDF
60 70 80 90 100
NKRLDEWVTH ERLDLKKIQF PKKEAKTPTK NGLPGSRPGS PEREVPASAQ
110 120 130 140 150
ASGKTLPIPV QITLRFNLPK EREAIPGGEP DQPLSSSSCL QPNHRSTKRK
160 170 180 190 200
VEVVSPATPV PSETAPASVF PQNGSARRAV AAQPGRKRKS NCLGTDEDSQ
210 220 230 240 250
DSSDGIPSAP RMTGSLVSDR SHDDIVTRMK NIECIELGRH RLKPWYFSPY
260 270 280 290 300
PQELTTLPVL YLCEFCLKYG RSLKCLQRHL TKCDLRHPPG NEIYRKGTIS
310 320 330 340 350
FFEIDGRKNK SYSQNLCLLA KCFLDHKTLY YDTDPFLFYV MTEYDCKGFH
360 370 380 390 400
IVGYFSKEKE STEDYNVACI LTLPPYQRRG YGKLLIEFSY ELSKVEGKTG
410 420 430 440 450
TPEKPLSDLG LLSYRSYWSQ TILEILMGLK SESGERPQIT INEISEITSI
460 470 480 490 500
KKEDVISTLQ YLNLINYYKG QYILTLSEDI VDGHERAMLK RLLRIDSKCL
510
HFTPKDWSKR GKW
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.
InParanoidi Q8CHK4.
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.
ExpressionAtlasi Q8CHK4. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 114 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