Genome location: Pf3D7_08_v3:1,028,410..1,034,211(+)
Genome classification: Core
Product Description: histone acetyltransferase GCN5
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.3.1.48 (Histone acetyltransferase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0000123 | histone acetyltransferase complex |
| Component | GO:0005634 | nucleus |
| Function | GO:0010484 | H3 histone acetyltransferase activity |
| Function | GO:0005515 | protein binding |
| Function | GO:0003712 | transcription coregulator activity |
| Process | GO:0044409 | entry into host |
| Process | GO:0043966 | histone H3 acetylation |
| Process | GO:0080182 | histone H3-K4 trimethylation |
| Process | GO:0043970 | histone H3-K9 acetylation |
| Process | GO:0006355 | regulation of transcription, DNA-templated |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.96 | 0.57 |
| Trophozoite | expressed | 1.22 | 0.40 |
| Schizont | expressed | 0.66 | 0.62 |
| Gametocyte | possibly expressed | 0.72 | 0.62 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0823300
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 1 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.368 | MFS: -2.517 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0707300)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IB67
"Best" AlphaFill ligand hit: BU1 (1,4-butanediol, Local RMSD=0.02) with 5MKX (Global RMSD=1.04)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.3.1.48 | histone acetyltransferase | CoADNARNABF1EDTAMB-3LTK14PU139A-485TTK21CPTH2CPTH6... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q92831 | Histone acetyltransferase KAT2B | Homo sapiens | OrthoDB | US10155764, Example 1US10155764, Example 1AUS10155764, Example 1BUS10155764, Example 2... |
| Q92830 | Histone acetyltransferase KAT2A | OrthoDB | CHEMBL2177300CHEMBL4069412CHEMBL4069412CHEMBL106011... | |
| Q245K9 | Histone acetyltransferase | OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL4161210Ac-ARTKQTARKSTGGK(CoA)APRKQLCHEMBL4279596 | |
| Q03330 | Histone acetyltransferase GCN5 | OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL3416307CHEMBL3416308CHEMBL3416309CHEMBL3416310... |
Ortholog Group (OrthoMCL): OG6_101489
Most Similar Human Ortholog: K7EPC4
TM-align score: 0.92 | RMSD: 1.06
Seq Identity: 0.64 | Length: 70 / 1465
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000108773 | lysine acetyltransferase 2A |
| ENSG00000114166 | lysine acetyltransferase 2B |
Protein Length: 1465 | Molecular Weight (kDa): 170.918
Isoelectric Point: 6.64
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000182 | GNAT domain |
| InterPro | IPR001487 | Bromodomain |
| InterPro | IPR016181 | Acyl-CoA N-acyltransferase |
| InterPro | IPR036427 | Bromodomain-like superfamily |
| InterPro | IPR037800 | Histone acetyltransferase GCN5 |
| PFam | PF00583 | GNAT domain |
| Superfamily | SSF47370 | Bromodomain-like superfamily |
| Superfamily | SSF55729 | Acyl-CoA N-acyltransferase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 71 | 36 | 86 |
| disruptive | 47 | 181 | 96 | 251 |
| missense | 33 | 149 | 79 | 191 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 21 | 145 | 62 | 112 |
| disruptive | 92 | 472 | 211 | 501 |
| missense | 60 | 348 | 148 | 261 |
PlasmoDB Total SNPs: 319
Non-coding: 158 | Synonymous: 94 | Nonsynonymous: 67 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 15075257 | Plasmodium falciparum histone acetyltransferase, a yeast GCN5 homologue involvedin chromatin remodeling. | Fan Q, An L, Cui L | 10.1128/EC.3.2.264-276.2004 |
| 15246536 | PfADA2, a Plasmodium falciparum homologue of the transcriptional coactivator ADA2and its in vivo association with the histone acetyltransferase PfGCN5. | Fan Q, An L, Cui L | 10.1016/j.gene.2004.04.005 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 18692528 | 5' sequence- and chromatin modification-dependent gene expression in Plasmodiumfalciparum erythrocytic stage. | Komaki-Yasuda K, Okuwaki M, ..., Kawazu S | https://pubmed.ncbi.nlm.nih.gov/18692528/ |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 29631126 | Activity of bromodomain protein inhibitors/binders against asexual-stagePlasmodium falciparum parasites. | Chua MJ, Robaa D, ..., Andrews KT | 10.1016/j.ijpddr.2018.03.001 |
| 31728527 | Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum. | Hoeijmakers WAM, Miao J, ..., Bartfai R | 10.1093/nar/gkz1044 |
| 31965989 | Role of Pf GCN5 in nutrient sensing and transcriptional regulation in Plasmodiumfalciparum | Rawat M, Malhotra R, ..., Karmodiya K | https://pubmed.ncbi.nlm.nih.gov/31965989/ |
| 33441725 | Histone acetyltransferase PfGCN5 regulates stress responsive and artemisininresistance related genes in Plasmodium falciparum. | Rawat M, Kanyal A, ..., Karmodiya K | 10.1038/s41598-020-79539-w |
| 34403450 | A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion andvirulence in the malaria parasite Plasmodium falciparum. | Miao J, Wang C, ..., Cui L | 10.1371/journal.ppat.1009351 |
| 37702516 | Plasmodium falciparum GCN5 plays a key role in regulating artemisininresistance-related stress responses. | Lucky AB, Wang C, ..., Miao J | 10.1128/aac.00577-23 |
| 38142127 | Global deletome profile of Saccharomyces cerevisiae exposed to lithium | Fierling N, Billard P, Bauda P, Blaudez D | 10.1093/mtomcs/mfad073 |