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Protein

Histone acetyltransferase KAT5

Gene

KAT5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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. Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2. Promotes FOXP3 acetylation and positively regulates its transcriptional repressor activity (PubMed:17360565). Acetylates RAN at 'Lys-134' (PubMed:29040603).1 Publication11 Publications

Catalytic activityi

Acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei403Proton donor/acceptorBy similarity1
Binding sitei407Acetyl-CoA1 Publication1
Binding sitei416Acetyl-CoABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri260 – 285C2HC MYST-typePROSITE-ProRule annotation1 PublicationAdd BLAST26

GO - Molecular functioni

  • acetyltransferase activity Source: Reactome
  • androgen receptor binding Source: UniProtKB
  • histone acetyltransferase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • repressing transcription factor binding Source: BHF-UCL
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • beta-catenin-TCF complex assembly Source: Reactome
  • cellular response to estradiol stimulus Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
  • DNA double-strand break processing Source: Reactome
  • DNA replication Source: Reactome
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via nonhomologous end joining Source: Reactome
  • histone acetylation Source: UniProtKB
  • negative regulation of interleukin-2 production Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of protein acetylation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW
  • response to ionizing radiation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, Acyltransferase, Chromatin regulator, Transferase
Biological processGrowth regulation, Host-virus interaction, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-201722 Formation of the beta-catenin:TCF transactivating complex
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-3214847 HATs acetylate histones
R-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-5693548 Sensing of DNA Double Strand Breaks
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiQ92993
SIGNORiQ92993

Names & Taxonomyi

Protein namesi
Recommended name:
Histone acetyltransferase KAT5 (EC:2.3.1.483 Publications)
Alternative name(s):
60 kDa Tat-interactive protein
Short name:
Tip604 Publications
Histone acetyltransferase HTATIP
Short name:
HIV-1 Tat interactive protein
Lysine acetyltransferase 5
cPLA(2)-interacting protein
Gene namesi
Name:KAT5
Synonyms:HTATIP, TIP60
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000172977.12
HGNCiHGNC:5275 KAT5
MIMi601409 gene
neXtProtiNX_Q92993

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi86S → A: Reduces phosphorylation. Abolishes phosphorylation; when associated with A-90. Reduced HAT activity. 1 Publication1
Mutagenesisi90S → A: Reduces phosphorylation. Abolishes phosphorylation; when associated with A-86. Reduced HAT activity. 1 Publication1
Mutagenesisi254L → A: Does not affect phosphorylation; when associated with A-257. 1 Publication1
Mutagenesisi257L → A: Does not affect phosphorylation; when associated with A-254. 1 Publication1
Mutagenesisi380G → A: Loss of function. Does not affect phosphorylation. 1 Publication1
Mutagenesisi430K → R: Abrogates sumoylation. 1 Publication1
Mutagenesisi451K → R: Abrogates sumoylation. 1 Publication1

Organism-specific databases

DisGeNETi10524
OpenTargetsiENSG00000172977
PharmGKBiPA162392746

Chemistry databases

ChEMBLiCHEMBL5750
DrugBankiDB01992 Coenzyme A
DB02039 S-Acetyl-Cysteine
GuidetoPHARMACOLOGYi2664

Polymorphism and mutation databases

BioMutaiKAT5
DMDMi30923328

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000515801 – 513Histone acetyltransferase KAT5Add BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52N6-acetyllysineCombined sources1
Modified residuei86PhosphoserineCombined sources1 Publication1
Modified residuei90Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei199PhosphoserineCombined sources1
Modified residuei327N6-acetyllysine; by autocatalysis1 Publication1
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationi

(Microbial infection) In case of HIV-1 infection, interaction with the viral Tat protein leads to KAT5 polyubiquitination and targets it to degradation.1 Publication
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.1 Publication
Phosphorylated on Ser-86 and Ser-90; enhanced during G2/M phase. The phosphorylated form has a higher HAT activity.1 Publication
Ubiquitinated by MDM2, leading to its proteasome-dependent degradation.1 Publication
Autoacetylation at Lys-327 is required for proper function.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ92993
MaxQBiQ92993
PaxDbiQ92993
PeptideAtlasiQ92993
PRIDEiQ92993
ProteomicsDBi75654
75655 [Q92993-2]
75656 [Q92993-3]
75657 [Q92993-4]

PTM databases

iPTMnetiQ92993
PhosphoSitePlusiQ92993

Expressioni

Gene expression databases

BgeeiENSG00000172977
CleanExiHS_KAT5
ExpressionAtlasiQ92993 baseline and differential
GenevisibleiQ92993 HS

Organism-specific databases

HPAiHPA016953

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 (PubMed:12963728, PubMed:10966108, PubMed:15196461, PubMed:14966270). HTATTIP/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4. The NuA4 complex interacts with MYC. Interacts with ATM (PubMed:16141325). Interacts with JADE1 (PubMed:15502158). Interacts with PLA2G4A/CPLA2, EDNRA and HDAC7 (PubMed:11416127, PubMed:11262386, PubMed:12551922). Interacts with the cytoplasmic tail of APP and APBB1/FE65 (By similarity). Interacts with TRIM24 and TRIM68 (PubMed:18451177, PubMed:19909775). Forms a complex with SENP6 and UBE2I in response to UV irradiation. Identified in a complex with HINT1 (PubMed:16835243). Interacts with ATF2 and CUL3 (PubMed:18397884). Interacts with NR1D2 (via N-terminus) (PubMed:17996965). Component of a SWR1-like complex (PubMed:24463511). Interacts with FOXP3 (PubMed:17360565). Interacts with ZBTB49 (PubMed:25245946).1 PublicationBy similarity18 Publications
(Microbial infection) Interacts with HIV-1 TAT.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • repressing transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi115779, 229 interactors
ComplexPortaliCPX-709 Piccolo NuA4 histone acetyltransferase complex
CPX-978 NuA4 histone acetyltransferase complex
CORUMiQ92993
DIPiDIP-5998N
IntActiQ92993, 148 interactors
MINTiQ92993
STRINGi9606.ENSP00000340330

Chemistry databases

BindingDBiQ92993

Structurei

Secondary structure

1513
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 6Combined sources3
Beta strandi12 – 15Combined sources4
Beta strandi28 – 35Combined sources8
Beta strandi37 – 40Combined sources4
Beta strandi42 – 47Combined sources6
Helixi52 – 54Combined sources3
Beta strandi56 – 58Combined sources3
Helixi60 – 62Combined sources3
Helixi65 – 67Combined sources3
Beta strandi235 – 237Combined sources3
Beta strandi240 – 242Combined sources3
Helixi252 – 254Combined sources3
Beta strandi260 – 262Combined sources3
Turni264 – 266Combined sources3
Beta strandi269 – 271Combined sources3
Helixi273 – 282Combined sources10
Beta strandi289 – 296Combined sources8
Beta strandi299 – 305Combined sources7
Turni306 – 308Combined sources3
Helixi310 – 321Combined sources12
Beta strandi336 – 345Combined sources10
Beta strandi348 – 360Combined sources13
Beta strandi365 – 368Combined sources4
Beta strandi370 – 372Combined sources3
Helixi374 – 376Combined sources3
Helixi381 – 395Combined sources15
Beta strandi400 – 402Combined sources3
Helixi408 – 425Combined sources18
Helixi441 – 448Combined sources8
Helixi452 – 461Combined sources10
Beta strandi469 – 474Combined sources6
Helixi497 – 499Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EKONMR-A5-78[»]
2OU2X-ray2.30A227-506[»]
4QQGX-ray2.80A/B/C/D/E/F/G1-80[»]
ProteinModelPortaliQ92993
SMRiQ92993
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92993

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini227 – 504MYST-type HATPROSITE-ProRule annotationAdd BLAST278

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni368 – 513Interaction with ATF21 PublicationAdd BLAST146
Regioni370 – 372Acetyl-CoA binding1 Publication3
Regioni377 – 383Acetyl-CoA binding1 Publication7

Sequence similaritiesi

Belongs to the MYST (SAS/MOZ) family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri260 – 285C2HC MYST-typePROSITE-ProRule annotation1 PublicationAdd BLAST26

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2747 Eukaryota
COG5027 LUCA
GeneTreeiENSGT00920000148999
HOGENOMiHOG000182457
InParanoidiQ92993
KOiK11304
OMAiIRPWYFS
OrthoDBiEOG091G0B73
PhylomeDBiQ92993
TreeFamiTF317619

Family and domain databases

CDDicd00024 CHROMO, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016181 Acyl_CoA_acyltransferase
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR037995 Esa1/KAT5/Tip60
IPR002717 HAT_MYST-type
IPR025995 Tudor-knot
IPR036388 WH-like_DNA-bd_sf
PANTHERiPTHR10615:SF124 PTHR10615:SF124, 1 hit
PfamiView protein in Pfam
PF01853 MOZ_SAS, 1 hit
PF11717 Tudor-knot, 1 hit
SMARTiView protein in SMART
SM00298 CHROMO, 1 hit
SUPFAMiSSF54160 SSF54160, 1 hit
SSF55729 SSF55729, 1 hit
PROSITEiView protein in PROSITE
PS51726 MYST_HAT, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q92993-1) [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 PQNGAARRAV 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):58,582
Last modified:May 16, 2003 - v2
Checksum:i63724F5E10B957D5
GO
Isoform 1 (identifier: Q92993-2) [UniParc]FASTAAdd to basket
Also known as: PLIP

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

Show »
Length:461
Mass (Da):53,077
Checksum:i5A0E9324550AF246
GO
Isoform 3 (identifier: Q92993-3) [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):61,798
Checksum:i0CEB1A8E8C8D3E24
GO
Isoform 4 (identifier: Q92993-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     4-4: V → VVSPVPGAGRREPGEVGRARGPPVADPGVALSPQ
     96-147: Missing.

Note: No experimental confirmation available.
Show »
Length:494
Mass (Da):56,292
Checksum:i761BF5859BE89793
GO

Sequence cautioni

The sequence AAB02683 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti382G → R in AAB18236 (PubMed:8607265).Curated1
Sequence conflicti382G → R in AAB02683 (PubMed:8607265).Curated1
Isoform 3 (identifier: Q92993-3)
Sequence conflicti32V → A no nucleotide entry (PubMed:12801643).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05945678P → T. Corresponds to variant dbSNP:rs11541271Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0091044V → VVSPVPGAGRREPGEVGRAR GPPVADPGVALSPQ in isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_00743896 – 147Missing in isoform 1 and isoform 4. 3 PublicationsAdd BLAST52

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U74667 mRNA Translation: AAB18236.1
U40989 mRNA Translation: AAB02683.1 Different initiation.
U67734 mRNA Translation: AAD00163.1
AY214165 Genomic DNA Translation: AAO21130.1
AK304664 mRNA Translation: BAG65439.1
AP001266 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW74427.1
CH471076 Genomic DNA Translation: EAW74429.1
BC000166 mRNA Translation: AAH00166.3
BC064912 mRNA Translation: AAH64912.1
BC093032 mRNA Translation: AAH93032.1
BC143296 mRNA Translation: AAI43297.1
BC117167 mRNA Translation: AAI17168.1
CCDSiCCDS31610.1 [Q92993-1]
CCDS55771.1 [Q92993-4]
CCDS8109.1 [Q92993-2]
CCDS8110.1 [Q92993-3]
RefSeqiNP_001193762.1, NM_001206833.1 [Q92993-4]
NP_006379.2, NM_006388.3 [Q92993-1]
NP_874368.1, NM_182709.2 [Q92993-2]
NP_874369.1, NM_182710.2 [Q92993-3]
UniGeneiHs.397010

Genome annotation databases

EnsembliENST00000341318; ENSP00000340330; ENSG00000172977 [Q92993-3]
ENST00000352980; ENSP00000344955; ENSG00000172977 [Q92993-2]
ENST00000377046; ENSP00000366245; ENSG00000172977 [Q92993-1]
ENST00000530446; ENSP00000434765; ENSG00000172977 [Q92993-4]
GeneIDi10524
KEGGihsa:10524
UCSCiuc001ofi.4 human [Q92993-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKAT5_HUMAN
AccessioniPrimary (citable) accession number: Q92993
Secondary accession number(s): B4E3C7
, C9JL99, O95624, Q13430, Q17RW5, Q561W3, Q6GSE8, Q9BWK7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 16, 2003
Last modified: June 20, 2018
This is version 196 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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