KAT2A

Official Full Name

lysine acetyltransferase 2A

Organism

Homo sapiens

Gene ID

2648

Background

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]

Synonyms

GCN5; hGCN5; GCN5L2; PCAF-b

Cat.No.	Product Name	Price
CSC-DC005002	Panoply™ Human EPM2AIP1 Knockdown Stable Cell Line	Inquiry
CSC-DC007894	Panoply™ Human KAT2A Knockdown Stable Cell Line	Inquiry
CSC-SC005002	Panoply™ Human EPM2AIP1 Over-expressing Stable Cell Line	Inquiry
CSC-SC007894	Panoply™ Human KAT2A Over-expressing Stable Cell Line	Inquiry
CSC-RT1730	Human KAT2A Knockout Cell Line-HEK293T	Inquiry
CLKO-1577	KAT2A KO Cell Lysate-HEK293T	Inquiry

Cat.No.	Product Name	Price
AD05537Z	Human EPM2AIP1 adenoviral particles	Inquiry
AD08354Z	Human KAT2A adenoviral particles	Inquiry
LV11847L	human EPM2AIP1 (NM_014805) lentivirus particles	Inquiry
LV15877L	human KAT2A (NM_021078) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH036623	shRNA set against Mouse Epm2aip1(NM_175266.4)	Inquiry
SHH080219	shRNA set against Human GCN5L2(NM_021078.2)	Inquiry
SHH286557	shRNA set against Human EPM2AIP1 (NM_014805.3)	Inquiry
SHH286561	shRNA set against Mouse EPM2AIP1 (NM_175266.4)	Inquiry
SHH322415	shRNA set against Human KAT2A (NM_021078.2)	Inquiry
SHH322419	shRNA set against Mouse KAT2A (NM_020004.5)	Inquiry
SHH322423	shRNA set against Rat KAT2A (NM_001107050.1)	Inquiry

Cat.No.	Product Name	Price
CDCL122589	Human KAT2A ORF clone (NM_021078.2)	Inquiry
CDFR006760	Rat Kat2a cDNA Clone(NM_001107050.1)	Inquiry
MiUTR1H-03989	KAT2A miRNA 3'UTR clone	Inquiry
MiUTR1M-04438	EPM2AIP1 miRNA 3'UTR clone	Inquiry
CDCB158342	Human EPM2AIP1 ORF clone (BC064696)	Inquiry
CDCB181507	Rabbit EPM2AIP1 ORF clone (XM_008266130.1)	Inquiry
CDCB189150	Rabbit KAT2A ORF clone (XM_008271494.1)	Inquiry
CDCH018751	Mouse EPM2AIP1 ORF clone(NM_175266.4)	Inquiry
CDCR232960	Mouse Kat2a ORF Clone(NM_001038010.2)	Inquiry
CDCR254684	Mouse Kat2a ORF Clone(NM_020004.5)	Inquiry
CDCR373783	Rat Kat2a ORF Clone(NM_001107050.1)	Inquiry
CDCS413785	Human EPM2AIP1 ORF Clone (BC064696)	Inquiry
CDCS415263	Human KAT2A ORF Clone (BC032743)	Inquiry

Detailed Information

Recent Research

KAT2A, a member of the GCN5-related N- acetyltransferase (GNAT) superfamily, was identified as a histone acetyltransferase (HAT) that binds to acetyl-CoA and transfers its acetyl group to histones. The α-ketoglutarate dehydrogenase (α- KGDH) complex is localized in the nucleus in human cell lines and binds to KAT2A in the promoter regions of genes. Some reports showed that the crystal structure of the catalytic domain of KAT2A in complex with succinyl-coenzyme A (succinyl-CoA) at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. CoA competes with succinyl-CoA to bind to KAT2A and that the CoA group in succinyl-CoA is involved in its interaction with KAT2A. KAT2A acts as succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expresses KAT2A, reduces gene expression and inhibits tumor cell proliferation and tumor growth. It has been demonstrated that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumor cell proliferation and tumor development.

Some reports showed that KAT2A and KAT2B regulate TBX5 transcriptional activity. TBX5, a T-box transcription factor, is a master regulator of cardiac development. In fact, both KAT2A and KAT2B physically interact with TBX5 in vitro and acetylate it at Lys339. Acetylation enhances its transcriptional activity and is necessary for its nuclear output. While in vivo, knockdown of KAT2A or KAT2B produced both heart and fin phenotypes similar to that observed in TBX5 mutants, which includes incomplete heart looping, pericardial oedema, lack of blood flow into the heart and absence of functional fins.

KAT2A and KAT2B are mainly studied as HATs that acetylate preferentially histone H3 and to a lesser extent H4, leading to changes in chromatin structure. However, KAT2A/KAT2B can also function as a repressor of NF-kappa-B by promoting ubiquitination of the NF-kappa-B subunit RELA in a HAT-independent manner. Recently, it has found one KAT2A/2B substrate, polo-like kinase 4 (PLK4), a key regulator of centrosome duplication. It has been shown that KAT2A/2B acetylates the PLK4 kinase domain on residues K45 and K46. Molecular dynamics modelling suggests that K45/K46 acetylation impairs kinase activity by shifting the kinase to an inactive conformation. Accordingly, PLK4 activity is reduced upon in vitro acetylation of its kinase domain. Moreover, the over-expression of the PLK4 K45R/K46R mutant in cells does not lead to centrosome over-ampliﬁcation. Impairing KAT2A/2B- acetyltransferase activity results in diminished phosphorylation of PLK4 and in excess centrosome numbers in cells.

References:

Ghosh T K, et al. Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development. Journal of Molecular & Cellular Cardiology, 2018, 114.
Fournier M, et al. KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nature Communications, 2016, 7:13227.
Wang Y, et al. KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase. Nature, 2017, 552(7684):273-277.
Li T, Su L, et al. DDIT3 and KAT2A Proteins Regulate TNFRSF10A and TNFRSF10B Expression in Endoplasmic Reticulum Stress-mediated Apoptosis in Human Lung Cancer Cells. Journal of Biological Chemistry, 2015, 290(17):11108.

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