EzCatDB: M00165
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DB codeM00165
RLCP classification3.1147.6000.72 : Transfer
CATH domainDomain 1-.-.-.-
Domain 2-.-.-.-
Domain 3-.-.-.-
Domain 43.40.630.30 : AminopeptidaseCatalytic domain
Domain 5-.-.-.-
Domain 61.20.920.10 : Histone Acetyltransferase; Chain A
E.C.2.3.1.48
CSA1cm0

CATH domainRelated DB codes (homologues)
3.40.630.30 : AminopeptidaseS00409,S00410,D00413,T00034

Enzyme Name
UniProtKBKEGG

Q92830Q92831
Protein nameGeneral control of amino acid synthesis protein 5-like 2Histone acetyltransferase PCAFhistone acetyltransferase
nucleosome-histone acetyltransferase
histone acetokinase
histone acetylase
histone transacetylase
SynonymsEC 2.3.1.48
Histone acetyltransferase GCN5
hsGCN5
STAF97
Histone acetylase PCAF
EC 2.3.1.48
P300/CBP-associated factor
P/CAF
RefSeqNP_066564.2 (Protein)
NM_021078.2 (DNA/RNA sequence)
NP_003875.3 (Protein)
NM_003884.4 (DNA/RNA sequence)
PfamPF00583 (Acetyltransf_1)
PF00439 (Bromodomain)
PF06466 (PCAF_N)
[Graphical view]
PF13508 (Acetyltransf_7)
PF00439 (Bromodomain)
PF06466 (PCAF_N)
[Graphical view]


UniProtKB:Accession NumberQ92830Q92831
Entry nameGCNL2_HUMANPCAF_HUMAN
ActivityAcetyl-CoA + histone = CoA + acetylhistone.Acetyl-CoA + histone = CoA + acetylhistone.
SubunitInteracts with EP300, CREBBP and ADA2. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, GCN5L2/GCN5, TAF10 and TRRAP. Interacts with TRRAP. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Interacts with and acetylates HIV-1 Tat.Interacts with SIRT1 (By similarity). Interacts with EP300 and CREBBP. Interacts with NCOA1 and NCOA3. Binds to HTLV-1 Tax. Interacts with and acetylates HIV-1 Tat. Interacts with KLF1, the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4.
Subcellular locationNucleus.Nucleus (By similarity).
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00024C01429C00010C01997
CompoundAcetyl-CoAHistoneCoAAcetylhistone
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfide grouppeptide/proteinamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl grouppeptide/protein
ChEBI15351

15346

PubChem6302
444493

87642
6816

            
1cm0AUnboundUnboundBound:COAUnbound
1cm0BUnboundUnboundBound:COAUnbound
1b91AUnboundUnboundUnboundUnbound
1jm4BUnboundUnboundUnboundUnbound
1f68AUnboundUnboundUnboundUnbound
1n72AUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [2]
pdbCatalytic residuesMain-chain involved in catalysis
          
1cm0AGLU 570
CYS 574
1cm0BGLU 570
CYS 574
1b91A 
 
1jm4B 
 
1f68A 
 
1n72A 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.4C, p.3526-3528
[3]Fig.4, p.18160
[14]p.157-158
[17]Fig.3, p.438
[20]Fig.2E, p.556
[21]Fig.3A, p.115

references
[1]
PubMed ID8684459
JournalNature
Year1996
Volume382
Pages319-24
AuthorsYang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y
TitleA p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A
[2]
PubMed ID10393169
JournalEMBO J
Year1999
Volume18
Pages3521-32
AuthorsClements A, Rojas JR, Trievel RC, Wang L, Berger SL, Marmorstein R
TitleCrystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A
Related PDB1cm0
[3]
PubMed ID10373413
JournalJ Biol Chem
Year1999
Volume274
Pages18157-60
AuthorsTanner KG, Trievel RC, Kuo MH, Howard RM, Berger SL, Allis CD, Marmorstein R, Denu JM
TitleCatalytic mechanism and function of invariant glutamic acid 173 from the histone acetyltransferase GCN5 transcriptional coactivator
[4]
CommentsSTRUCTURE BY NMR OF 715-832, AND MUTAGENESIS OF VAL-752; TYR-760; TYR-802 AND TYR-809.
Medline ID99292086
PubMed ID10365964
JournalNature
Year1999
Volume399
Pages491-6
AuthorsDhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM
TitleStructure and ligand of a histone acetyltransferase bromodomain
Related PDB1b91,1n72
Related UniProtKBQ92831
[5]
PubMed ID10430845
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages8807-8
AuthorsSternglanz R, Schindelin H
TitleStructure and mechanism of action of the histone acetyltransferase Gcn5 and similarity to other N-acetyltransferases.
[6]
PubMed ID11009610
JournalBiochemistry
Year2000
Volume39
Pages11961-9
AuthorsTanner KG, Langer MR, Denu JM
TitleKinetic mechanism of human histone acetyltransferase P/CAF
[7]
PubMed ID10648382
JournalBlood
Year2000
Volume95
Pages745-55
AuthorsBlobel GA
TitleCREB-binding protein and p300
[8]
PubMed ID10777508
JournalJ Biol Chem
Year2000
Volume275
Pages21953-9
AuthorsLau OD, Courtney AD, Vassilev A, Marzilli LA, Cotter RJ, Nakatani Y, Cole PA
Titlep300/CBP-associated factor histone acetyltransferase processing of a peptide substrate. Kinetic analysis of the catalytic mechanism
[9]
CommentsSTRUCTURE BY NMR OF 730-832.
PubMed ID11090279
JournalJ Mol Biol
Year2000
Volume304
Pages355-70
AuthorsHudson BP, Martinez-Yamout MA, Dyson HJ, Wright PE
TitleSolution structure and acetyl-lysine binding activity of the GCN5 bromodomain
Related PDB1f68
Related UniProtKBQ92830
[10]
PubMed ID10839822
JournalMicrobiol Mol Biol Rev
Year2000
Volume64
Pages435-59
AuthorsSterner DE, Berger SL
TitleAcetylation of histones and transcription-related factors.
[11]
CommentsINTERACTION WITH TRRAP.
Medline ID10611234
PubMed ID10611234
JournalMol Cell Biol
Year2000
Volume20
Pages556-62
AuthorsMcMahon SB, Wood MA, Cole MD
TitleThe essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.
Related UniProtKBQ92830
[12]
PubMed ID10847852
JournalScience
Year2000
Volume288
Pages1372-3
AuthorsPennisi E
TitleMatching the transcription machinery to the right DNA
[13]
PubMed ID11437231
JournalCell Mol Life Sci
Year2001
Volume58
Pages693-703
AuthorsMarmorstein R
TitleStructure and function of histone acetyltransferases
[14]
PubMed ID11250138
JournalCurr Opin Genet Dev
Year2001
Volume11
Pages155-61
AuthorsMarmorstein R, Roth SY
TitleHistone acetyltransferases
[15]
PubMed ID11509556
JournalJ Biol Chem
Year2001
Volume276
Pages42753-60
AuthorsShankaranarayanan P, Chaitidis P, Kuhn H, Nigam S
TitleAcetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is required for transcriptional activation of the 15-lipoxygenase-1 gene
[16]
PubMed ID11445580
JournalJ Biol Chem
Year2001
Volume276
Pages33721-9
AuthorsThompson PR, Kurooka H, Nakatani Y, Cole PA
TitleTranscriptional coactivator protein p300. Kinetic characterization of its histone acetyltransferase activity
[17]
PubMed ID11492997
JournalJ Mol Biol
Year2001
Volume311
Pages433-44
AuthorsMarmorstein R
TitleStructure of histone acetyltransferases.
[18]
PubMed ID11911891
JournalFEBS Lett
Year2002
Volume513
Pages124-8
AuthorsZeng L, Zhou MM
TitleBromodomain: an acetyl-lysine binding domain.
[19]
CommentsNMR structure
PubMed ID11931765
JournalMol Cell
Year2002
Volume9
Pages575-86
AuthorsMujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM
TitleStructural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.
Related PDB1jm4
[20]
PubMed ID14712728
JournalMethods Enzymol
Year2003
Volume371
Pages545-64
AuthorsClements A, Marmorstein R
TitleInsights into structure and function of GCN5/PCAF and yEsa 1 histone acetyltransferase domains:.
[21]
PubMed ID14975301
JournalMethods Enzymol
Year2004
Volume376
Pages106-19
AuthorsMarmorstein R
TitleBiochemical and structural characterization of recombinant histone acetyltransferase proteins.
[22]
PubMed ID14975302
JournalMethods Enzymol
Year2004
Volume376
Pages119-30
AuthorsMujtaba S, Zhou MM
TitleUse of nuclear magnetic resonance spectroscopy to study structure-function of bromodomains.

comments
According to the literature [2], the catalytic mechanism is similar to that of histone acetyltransferase type B (T00034 in EzCatDB). The reaction proceeds via a direct nucleophilic attack of the substrate histone lysine on the carbonyl carbon of acyl group of acetyl-CoA (see [2]).
Hydrophobic residues (Phe563, Phe568, Ile571, Val572, Leu606, Ile637 & Tyr640) raise the pKa of the general base, Glu570. The mainchain amide of Cys574 stabilizes the tetrahedral intermediate.

createdupdated
2005-01-242009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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