Genome location: Pf3D7_13_v3:1,213,757..1,216,004(+)
Genome classification: Core
Product Description: transcriptional regulatory protein sir2a
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:0005677 | chromatin silencing complex |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005730 | nucleolus |
| Component | GO:0005634 | nucleus |
| Function | GO:0003677 | DNA binding |
| Function | GO:0070403 | NAD+ binding |
| Function | GO:0017136 | NAD-dependent histone deacetylase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0006342 | chromatin silencing |
| Process | GO:0006355 | regulation of transcription, DNA-templated |
| Process | GO:0016233 | telomere capping |
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 | 0.26 | 0.87 |
| Trophozoite | expressed | 0.16 | 0.91 |
| Schizont | expressed | 0.56 | 0.67 |
| Gametocyte | expressed | 0.54 | 0.71 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1328800
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: -2.06 | #Insertions: 2
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1343800)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1343800)
Modification: Tagged | RMgm-4440
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IE47
"Best" AlphaFill ligand hit: NCA (nicotinamide, Local RMSD=0.04) with 1YC2 (Global RMSD=2.53)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9NXA8 | NAD-dependent protein deacylase sirtuin-5, mitochondrial | OMA, OrthoDB, OrthoMCL BLAST | Suramin hexasodiumSuramin hexasodiumCHEMBL3601368CHEMBL4100475... |
Ortholog Group (OrthoMCL): OG6_102326
Most Similar Human Ortholog: Q9NXA8
TM-align score: 0.85 | RMSD: 2.74
Seq Identity: 0.28 | Length: 261 / 273
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000124523 | sirtuin 5 |
Protein Length: 273 | Molecular Weight (kDa): 30.344
UniProt ID(s): Q8IE47
Isoelectric Point: 8.62
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003000 | Sirtuin family |
| InterPro | IPR027546 | Sirtuin, class III |
| 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 | 2 | 10 | 4 | 17 |
| disruptive | 2 | 7 | 2 | 23 |
| missense | 2 | 6 | 1 | 22 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 20 | 13 | 18 |
| disruptive | 4 | 20 | 17 | 41 |
| missense | 2 | 14 | 13 | 34 |
PlasmoDB Total SNPs: 105
Non-coding: 96 | Synonymous: 6 | Nonsynonymous: 3 | 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 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 15820676 | Telomeric heterochromatin propagation and histone acetylation control mutuallyexclusive expression of antigenic variation genes in malaria parasites. | Freitas-Junior LH, Hernandez-Rivas R, ..., Scherf A | 10.1016/j.cell.2005.01.037 |
| 17827348 | Plasmodium falciparum Sir2: an unusual sirtuin with dual histone deacetylase andADP-ribosyltransferase activity. | Merrick CJ, Duraisingh MT | 10.1128/EC.00114-07 |
| 18221799 | Biochemical characterization of Plasmodium falciparum Sir2, a NAD+-dependentdeacetylase. | Chakrabarty SP, Saikumari YK, Bopanna MP, Balaram H | 10.1016/j.molbiopara.2007.12.003 |
| 18397290 | Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasitegrowth. | Prusty D, Mehra P, ..., Dhar SK | 10.1111/j.1574-6968.2008.01135.x |
| 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 |
| 18547337 | Identification of a novel post-translational modification in Plasmodiumfalciparum: protein sumoylation in different cellular compartments. | Issar N, Roux E, Mattei D, Scherf A | 10.1111/j.1462-5822.2008.01183.x |
| 18729382 | Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and anacetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase. | French JB, Cen Y, Sauve AA | 10.1021/bi800767t |
| 19402747 | Sir2 paralogues cooperate to regulate virulence genes and antigenic variation inPlasmodium falciparum. | Tonkin CJ, Carret CK, ..., Cowman AF | 10.1371/journal.pbio.1000084 |
| 20601220 | Reversible binding of zinc in Plasmodium falciparum Sir2: structure and activityof the apoenzyme. | Chakrabarty SP, Balaram H | 10.1016/j.bbapap.2010.06.010 |
| 21992006 | Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fattyacyl lysine. | Zhu AY, Zhou Y, ..., Lin H | 10.1021/cb200230x |
| 22006844 | Identification and molecular characterization of an Alba-family protein fromhuman malaria parasite Plasmodium falciparum. | Goyal M, Alam A, ..., Bandyopadhyay U | 10.1093/nar/gkr821 |
| 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 |
| 12618394 | Short-chain fatty acid activation by acyl-coenzyme A synthetases requires SIR2protein function in Salmonella enterica and Saccharomyces cerevisiae | Starai VJ, Takahashi H, Boeke JD, Escalante-Semerena JC | 10.1093/genetics/163.2.545 |
| 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 |
| 35510853 | A Leak-Free Inducible CRISPRi/a System for Gene Functional Studies in Plasmodiumfalciparum | Liang X, Boonhok R, ..., Miao J | 10.1128/spectrum.02782-21 |
| 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 |