KAT2A (lysine acetyltransferase 2A)

Gene

• Entrez ID: 2648
• Gene name: Lysine acetyltransferase 2A
• Gene symbol: KAT2A
• Synonyms: GCN5, GCN5L2, PCAF-b, hGCN5
• Chromosome: 17
• Chromosome location: 17q21.2
• Summary: KAT2A, or GCN5, is a histone acetyltransferase (HAT) that functions primarily as a transcriptional activator. It also functions as a repressor of NF-kappa-B (see MIM 164011) by promoting ubiquitination of the NF-kappa-B subunit RELA (MIM 164014) in a HAT-independent manner (Mao et al., 2009 [PubMed 19339690]).[supplied by OMIM, Sep 2009]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022532	hsa-miR-124-3p	Microarray	18668037
MIRT023698	hsa-miR-1-3p	Microarray	18668037
MIRT039857	hsa-miR-615-3p	CLASH	23622248
MIRT043446	hsa-miR-331-3p	CLASH	23622248
MIRT047064	hsa-miR-183-5p	CLASH	23622248
MIRT049612	hsa-miR-92a-3p	CLASH, qRT-PCR	23622248
MIRT050843	hsa-miR-17-5p	CLASH	23622248
MIRT437521	hsa-miR-19b-3p	Immunoprecipitaion	22382630

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000123	Component	Histone acetyltransferase complex	IDA	29973595, 31527837
GO:0001701	Process	In utero embryonic development	IEA
GO:0001756	Process	Somitogenesis	IEA
GO:0001816	Process	Cytokine production	ISS
GO:0001843	Process	Neural tube closure	IEA
GO:0003682	Function	Chromatin binding	IDA	29211711
GO:0003713	Function	Transcription coactivator activity	IDA	11564863, 29211711, 29973595, 31527837
GO:0004402	Function	Histone acetyltransferase activity	IDA	10373431, 11564863, 29211711, 31527837
GO:0004402	Function	Histone acetyltransferase activity	TAS
GO:0005515	Function	Protein binding	IPI	17664281, 20562830, 20972224, 21725360, 24502362, 27796307, 29174768, 29232376, 29973595, 31527837
GO:0005615	Component	Extracellular space	HDA	22664934
GO:0005634	Component	Nucleus	IDA	11564863, 27796307, 29211711
GO:0005654	Component	Nucleoplasm	TAS
GO:0005671	Component	Ada2/Gcn5/Ada3 transcription activator complex	IDA	18838386
GO:0005694	Component	Chromosome	IEA
GO:0005813	Component	Centrosome	IDA	27796307
GO:0006338	Process	Chromatin remodeling	TAS	8552087
GO:0006357	Process	Regulation of transcription by RNA polymerase II	TAS	8552087
GO:0007507	Process	Heart development	ISS
GO:0007616	Process	Long-term memory	ISS
GO:0008134	Function	Transcription factor binding	IPI	17301242
GO:0008283	Process	Cell population proliferation	IEA
GO:0010484	Function	H3 histone acetyltransferase activity	IDA	18838386
GO:0014070	Process	Response to organic cyclic compound	IEA
GO:0016032	Process	Viral process	IEA
GO:0016573	Process	Histone acetylation	IDA	29973595, 31527837
GO:0016578	Process	Histone deubiquitination	IDA	18206972
GO:0016579	Process	Protein deubiquitination	TAS
GO:0018215	Process	Protein phosphopantetheinylation	IEA
GO:0018393	Process	Internal peptidyl-lysine acetylation	IDA	27796307, 29174768
GO:0019903	Function	Protein phosphatase binding	IEA
GO:0021537	Process	Telencephalon development	IEA
GO:0022037	Process	Metencephalon development	IEA
GO:0030901	Process	Midbrain development	IEA
GO:0030914	Component	STAGA complex	IDA	11564863
GO:0031346	Process	Positive regulation of cell projection organization	IEA
GO:0031647	Process	Regulation of protein stability	IMP	20562830
GO:0031667	Process	Response to nutrient levels	IEA
GO:0033276	Component	Transcription factor TFTC complex	IDA	10373431
GO:0035066	Process	Positive regulation of histone acetylation	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0042826	Function	Histone deacetylase binding	IPI	12887892
GO:0043966	Process	Histone H3 acetylation	IDA	10373431, 11564863, 18838386, 29211711
GO:0043983	Process	Histone H4-K12 acetylation	IEA
GO:0043997	Function	Histone acetyltransferase activity (H4-K12 specific)	IEA
GO:0044154	Process	Histone H3-K14 acetylation	IEA
GO:0045252	Component	Oxoglutarate dehydrogenase complex	IDA	29211711
GO:0045589	Process	Regulation of regulatory T cell differentiation	ISS
GO:0045722	Process	Positive regulation of gluconeogenesis	IEA
GO:0045815	Process	Positive regulation of gene expression, epigenetic	TAS
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	29973595, 31527837
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	29211711
GO:0046600	Process	Negative regulation of centriole replication	IDA	27796307
GO:0048167	Process	Regulation of synaptic plasticity	ISS
GO:0048312	Process	Intracellular distribution of mitochondria	IEA
GO:0050863	Process	Regulation of T cell activation	ISS
GO:0060173	Process	Limb development	ISS
GO:0061035	Process	Regulation of cartilage development	ISS
GO:0061733	Function	Peptide-lysine-N-acetyltransferase activity	IDA	27796307, 29174768
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071929	Process	Alpha-tubulin acetylation	IEA
GO:0072686	Component	Mitotic spindle	IEA
GO:0106077	Process	Histone succinylation	IDA	29211711
GO:0106078	Function	Histone succinyltransferase activity	IDA	29211711
GO:0106227	Process	Peptidyl-lysine glutarylation	IDA	31542297
GO:0106229	Function	Histone glutaryltransferase activity	IDA	31542297
GO:1903010	Process	Regulation of bone development	ISS
GO:1990090	Process	Cellular response to nerve growth factor stimulus	IEA
GO:2000036	Process	Regulation of stem cell population maintenance	ISS
GO:2000727	Process	Positive regulation of cardiac muscle cell differentiation	IEA

Other IDs

• MIM: 602301
• HGNC: 4201
• e!Ensembl: ENSG00000108773

Protein

• UniProt ID: Q92830
• Protein name: Histone acetyltransferase KAT2A (EC 2.3.1.48) (General control of amino acid synthesis protein 5-like 2) (Histone acetyltransferase GCN5) (hGCN5) (Histone glutaryltransferase KAT2A) (EC 2.3.1.-) (Histone succinyltransferase KAT2A) (EC 2.3.1.-) (Lysine acetyltransferase 2A) (STAF97)
• Protein function: Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:29211711). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242, PubMed:27796307, PubMed:29174768). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed:31542297). ; (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.
• PDB: 1F68, 1Z4R, 3D7C, 5H84, 5H86, 5MLJ, 5TRL, 5TRM, 6J3P
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06466	PCAF_N	86 → 336	PCAF (P300/CBP-associated factor) N-terminal domain	Domain
  PF00583	Acetyltransf_1	517 → 627	Acetyltransferase (GNAT) family	Family
  PF00439	Bromodomain	737 → 820	Bromodomain	Domain

• Sequence:

  MAEPSQAPTPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPAAAPAGSTGT
  GGPGVGSGGAGSGGDPARPGLSQQQRASQRKAQVRGLPRAKKLEKLGVFSACKANETCKC
  NGWKNPKPPTAPRMDLQQPAANLSELCRSCEHPLADHVSHLENVSEDEINRLLGMVVDVE
  NLFMSVHKEEDTDTKQVYFYLFKLLRKCILQMTRPVVEGSLGSPPFEKPNIEQGVLNFVQ
  YKFSHLAPRERQTMFELSKMFLLCLNYWKLETPAQFRQRSQAEDVATYKVNYTRWLCYCH
  VPQSCDSLPRYETTHVFGRSLLRSIFTVTRRQLLEKFRVEKDKLVPEKRTLILTHFPKFL
  SMLEEEIYGANSPIWESGFTMPPSEGTQLVPRPASVSAAVVPSTPIFSPSMGGGSNSSLS
  LDSAGAEPMPGEKRTLPENLTLEDAKRLRVMGDIPMELVNEVMLTITDPAAMLGPETSLL
  SANAARDETARLEERRGIIEFHVIGNSLTPKANRRVLLWLVGLQNVFSHQLPRMPKEYIA
  RLVFDPKHKTLALIKDGRVIGGICFRMFPTQGFTEIVFCAVTSNEQVKGYGTHLMNHLKE
  YHIKHNILYFLTYADEYAIGYFKKQGFSKDIKVPKSRYLGYIKDYEGATLMECELNPRIP
  YTELSHIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKEGVRQIPVESVPGIRETGWKPLG
  KEKGKELKDPDQLYTTLKNLLAQIKSHPSAWPFMEPVKKSEAPDYYEVIRFPIDLKTMTE
  RLRSRYYVTRKLFVADLQRVIANCREYNPPDSEYCRCASALEKFFYFKLKEGGLIDK

• Sequence length: 837

Pathways

KEGG:

Viral life cycle - HIV-1
Notch signaling pathway
Thyroid hormone signaling pathway
Human T-cell leukemia virus 1 infection
Viral carcinogenesis

Reactome:

Pre-NOTCH Transcription and Translation
NOTCH1 Intracellular Domain Regulates Transcription
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
Notch-HLH transcription pathway
B-WICH complex positively regulates rRNA expression
Ub-specific processing proteases
RUNX3 regulates NOTCH signaling
NOTCH3 Intracellular Domain Regulates Transcription
NOTCH4 Intracellular Domain Regulates Transcription

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778