DB code: M00165

RLCP classification 3.1147.6000.72 : Transfer
CATH domain -.-.-.- :
-.-.-.- :
-.-.-.- :
3.40.630.30 : Aminopeptidase Catalytic domain
-.-.-.- :
1.20.920.10 : Histone Acetyltransferase; Chain A
E.C. 2.3.1.48
CSA 1cm0
M-CSA 1cm0
MACiE

CATH domain Related DB codes (homologues)
3.40.630.30 : Aminopeptidase S00409 S00410 D00413 T00034

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q92830 General control of amino acid synthesis protein 5-like 2
EC 2.3.1.48
Histone acetyltransferase GCN5
hsGCN5
STAF97
NP_066564.2 (Protein)
NM_021078.2 (DNA/RNA sequence)
PF00583 (Acetyltransf_1)
PF00439 (Bromodomain)
PF06466 (PCAF_N)
[Graphical View]
Q92831 Histone acetyltransferase PCAF
Histone acetylase PCAF
EC 2.3.1.48
P300/CBP-associated factor
P/CAF
NP_003875.3 (Protein)
NM_003884.4 (DNA/RNA sequence)
PF13508 (Acetyltransf_7)
PF00439 (Bromodomain)
PF06466 (PCAF_N)
[Graphical View]

KEGG enzyme name
histone acetyltransferase
nucleosome-histone acetyltransferase
histone acetokinase
histone acetylase
histone transacetylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q92830 GCNL2_HUMAN Acetyl-CoA + histone = CoA + acetylhistone. Interacts 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. Nucleus.
Q92831 PCAF_HUMAN Acetyl-CoA + histone = CoA + acetylhistone. 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. Nucleus (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00024 C01429 C00010 C01997
E.C.
Compound Acetyl-CoA Histone CoA Acetylhistone
Type amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group peptide/protein amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group peptide/protein
ChEBI 15351
 15351
 		15346
 15346
PubChem 444493
 6302
 444493
 6302
 		6816
 87642
 6816
 87642
1cm0A Unbound Unbound Bound:COA Unbound
1cm0B Unbound Unbound Bound:COA Unbound
1b91A Unbound Unbound Unbound Unbound
1jm4B Unbound Unbound Unbound Unbound
1f68A Unbound Unbound Unbound Unbound
1n72A Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cm0A GLU 570 CYS 574
1cm0B GLU 570 CYS 574
1b91A
1jm4B
1f68A
1n72A

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 8684459
Journal Nature
Year 1996
Volume 382
Pages 319-24
Authors Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y
Title A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10393169
Journal EMBO J
Year 1999
Volume 18
Pages 3521-32
Authors Clements A, Rojas JR, Trievel RC, Wang L, Berger SL, Marmorstein R
Title Crystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A
Related PDB 1cm0
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10373413
Journal J Biol Chem
Year 1999
Volume 274
Pages 18157-60
Authors Tanner KG, Trievel RC, Kuo MH, Howard RM, Berger SL, Allis CD, Marmorstein R, Denu JM
Title Catalytic mechanism and function of invariant glutamic acid 173 from the histone acetyltransferase GCN5 transcriptional coactivator
Related PDB
Related UniProtKB
[4]
Resource
Comments STRUCTURE BY NMR OF 715-832, AND MUTAGENESIS OF VAL-752; TYR-760; TYR-802 AND TYR-809.
Medline ID 99292086
PubMed ID 10365964
Journal Nature
Year 1999
Volume 399
Pages 491-6
Authors Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM
Title Structure and ligand of a histone acetyltransferase bromodomain
Related PDB 1b91 1n72
Related UniProtKB Q92831
[5]
Resource
Comments
Medline ID
PubMed ID 10430845
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 8807-8
Authors Sternglanz R, Schindelin H
Title Structure and mechanism of action of the histone acetyltransferase Gcn5 and similarity to other N-acetyltransferases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11009610
Journal Biochemistry
Year 2000
Volume 39
Pages 11961-9
Authors Tanner KG, Langer MR, Denu JM
Title Kinetic mechanism of human histone acetyltransferase P/CAF
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10648382
Journal Blood
Year 2000
Volume 95
Pages 745-55
Authors Blobel GA
Title CREB-binding protein and p300
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10777508
Journal J Biol Chem
Year 2000
Volume 275
Pages 21953-9
Authors Lau OD, Courtney AD, Vassilev A, Marzilli LA, Cotter RJ, Nakatani Y, Cole PA
Title p300/CBP-associated factor histone acetyltransferase processing of a peptide substrate. Kinetic analysis of the catalytic mechanism
Related PDB
Related UniProtKB
[9]
Resource
Comments STRUCTURE BY NMR OF 730-832.
Medline ID
PubMed ID 11090279
Journal J Mol Biol
Year 2000
Volume 304
Pages 355-70
Authors Hudson BP, Martinez-Yamout MA, Dyson HJ, Wright PE
Title Solution structure and acetyl-lysine binding activity of the GCN5 bromodomain
Related PDB 1f68
Related UniProtKB Q92830
[10]
Resource
Comments
Medline ID
PubMed ID 10839822
Journal Microbiol Mol Biol Rev
Year 2000
Volume 64
Pages 435-59
Authors Sterner DE, Berger SL
Title Acetylation of histones and transcription-related factors.
Related PDB
Related UniProtKB
[11]
Resource
Comments INTERACTION WITH TRRAP.
Medline ID 10611234
PubMed ID 10611234
Journal Mol Cell Biol
Year 2000
Volume 20
Pages 556-62
Authors McMahon SB, Wood MA, Cole MD
Title The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.
Related PDB
Related UniProtKB Q92830
[12]
Resource
Comments
Medline ID
PubMed ID 10847852
Journal Science
Year 2000
Volume 288
Pages 1372-3
Authors Pennisi E
Title Matching the transcription machinery to the right DNA
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11437231
Journal Cell Mol Life Sci
Year 2001
Volume 58
Pages 693-703
Authors Marmorstein R
Title Structure and function of histone acetyltransferases
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11250138
Journal Curr Opin Genet Dev
Year 2001
Volume 11
Pages 155-61
Authors Marmorstein R, Roth SY
Title Histone acetyltransferases
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11509556
Journal J Biol Chem
Year 2001
Volume 276
Pages 42753-60
Authors Shankaranarayanan P, Chaitidis P, Kuhn H, Nigam S
Title Acetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is required for transcriptional activation of the 15-lipoxygenase-1 gene
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11445580
Journal J Biol Chem
Year 2001
Volume 276
Pages 33721-9
Authors Thompson PR, Kurooka H, Nakatani Y, Cole PA
Title Transcriptional coactivator protein p300. Kinetic characterization of its histone acetyltransferase activity
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11492997
Journal J Mol Biol
Year 2001
Volume 311
Pages 433-44
Authors Marmorstein R
Title Structure of histone acetyltransferases.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11911891
Journal FEBS Lett
Year 2002
Volume 513
Pages 124-8
Authors Zeng L, Zhou MM
Title Bromodomain: an acetyl-lysine binding domain.
Related PDB
Related UniProtKB
[19]
Resource
Comments NMR structure
Medline ID
PubMed ID 11931765
Journal Mol Cell
Year 2002
Volume 9
Pages 575-86
Authors Mujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM
Title Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.
Related PDB 1jm4
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 14712728
Journal Methods Enzymol
Year 2003
Volume 371
Pages 545-64
Authors Clements A, Marmorstein R
Title Insights into structure and function of GCN5/PCAF and yEsa 1 histone acetyltransferase domains:.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 14975301
Journal Methods Enzymol
Year 2004
Volume 376
Pages 106-19
Authors Marmorstein R
Title Biochemical and structural characterization of recombinant histone acetyltransferase proteins.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 14975302
Journal Methods Enzymol
Year 2004
Volume 376
Pages 119-30
Authors Mujtaba S, Zhou MM
Title Use of nuclear magnetic resonance spectroscopy to study structure-function of bromodomains.
Related PDB
Related UniProtKB

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.

Created Updated
2005-01-24 2009-02-26