Genome location: Pf3D7_14_v3:2,107,995..2,113,322(+)
Genome classification: Core
Product Description: transcriptional regulatory protein sir2b
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.3.1.286 (Protein acetyllysine N-acetyltransferase);3.5.1.98 (Histone deacetylase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005634 | nucleus |
| Function | GO:0019213 | deacetylase activity |
| Function | GO:0004407 | histone deacetylase activity |
| Function | GO:0003714 | transcription corepressor activity |
| Process | GO:0070932 | histone H3 deacetylation |
| Process | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| Process | GO:0006355 | regulation of transcription, DNA-templated |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | not expressed | 0.21 | 0.90 |
| Trophozoite | possibly expressed | 0.50 | 0.70 |
| Schizont | not expressed | 0.07 | 0.95 |
| Gametocyte | not expressed | 0.27 | 0.84 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1451400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -0.804 | #Insertions: 4
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1315100)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1315100)
Modification: Disrupted | RMgm-4437
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKW2
"Best" AlphaFill ligand hit: NCA (nicotinamide, Local RMSD=0.04) with 1YC2 (Global RMSD=5.56)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
Ortholog Group (OrthoMCL): OG6_104149
Most Similar Human Ortholog: M0R1F6
TM-align score: 0.91 | RMSD: 1.70
Seq Identity: 0.34 | Length: 182 / 1304
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000077463 | sirtuin 6 |
Protein Length: 1304 | Molecular Weight (kDa): 154.72
UniProt ID(s): A0A144A2E0, Q8IKW2
PDB ID(s): None
Isoelectric Point: 8.01
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003000 | Sirtuin family |
| InterPro | IPR029035 | DHS-like NAD/FAD-binding domain superfamily |
| PFam | PF02146 | Sirtuin family |
| Superfamily | SSF52467 | DHS-like NAD/FAD-binding domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 21 | 88 | 42 | 98 |
| disruptive | 73 | 255 | 103 | 269 |
| missense | 46 | 208 | 89 | 205 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 34 | 165 | 62 | 111 |
| disruptive | 141 | 499 | 203 | 414 |
| missense | 89 | 385 | 159 | 229 |
PlasmoDB Total SNPs: 259
Non-coding: 60 | Synonymous: 103 | Nonsynonymous: 96 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 18525026 | Differential association of Orc1 and Sir2 proteins to telomeric domains inPlasmodium falciparum. | Mancio-Silva L, Rojas-Meza AP, ..., Hernandez-Rivas R | 10.1242/jcs.026427 |
| 19402747 | Sir2 paralogues cooperate to regulate virulence genes and antigenic variation inPlasmodium falciparum. | Tonkin CJ, Carret CK, ..., Cowman AF | 10.1371/journal.pbio.1000084 |
| 19666023 | The effect of Plasmodium falciparum Sir2a histone deacetylase on clonal andlongitudinal variation in expression of the var family of virulence genes. | Merrick CJ, Dzikowski R, ..., Duraisingh MT | 10.1016/j.ijpara.2009.06.012 |
| 23443558 | Sir2a regulates rDNA transcription and multiplication rate in the human malariaparasite Plasmodium falciparum. | Mancio-Silva L, Lopez-Rubio JJ, Claes A, Scherf A | 10.1038/ncomms2539 |
| 33538363 | Febrile temperature causes transcriptional downregulation of Plasmodiumfalciparum Sirtuins through Hsp90-dependent epigenetic modification. | Tabassum W, Bhattacharyya S, Varunan SM, Bhattacharyya MK | 10.1111/mmi.14692 |
| 35031386 | Alteration of the expression of sirtuins and var genes by heat shock in themalaria parasite Plasmodium falciparum | Anagu LO, Hulse DR, Horrocks PD, Chakravorty SJ | 10.1016/j.molbiopara.2022.111458 |
| 21379342 | Expression of P. falciparum var genes involves exchange of the histone variantH2A.Z at the promoter | Petter M, Lee CC, ..., Duffy MF | 10.1371/journal.ppat.1001292 |