Genome location: Pf3D7_07_v3:1,156,175..1,158,838(-)
Genome classification: Core
Product Description: cysteine desulfurase IscS
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.8.1.7 (Cysteine desulfurase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0004123 | cystathionine gamma-lyase activity |
| Function | GO:0031071 | cysteine desulfurase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0006534 | cysteine metabolic process |
| Process | GO:0016226 | iron-sulfur cluster assembly |
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 | 0.36 | 0.82 |
| Trophozoite | expressed | 0.28 | 0.84 |
| Schizont | possibly expressed | 0.05 | 0.97 |
| Gametocyte | expressed | 0.45 | 0.74 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0727200
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.335 | MFS: -2.553 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0211300)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IBI5
"Best" AlphaFill ligand hit: 8Q1 (s-[2-({n-[(2r)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate, Local RMSD=0.03) with 5WGB (Global RMSD=1.64)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.8.1.7 | cysteine desulfurase | NaBH4K2TeO3L-cysteineVinylglycineiodoacetamideD-cycloserinedithiothreitolL-AllylglycineN-ethylmaleimideL-selenocysteineinterferon-gammalipopolysaccharide... |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_100745
Most Similar Human Ortholog: F2Z2E7
TM-align score: 0.99 | RMSD: 0.56
Seq Identity: 0.54 | Length: 204 / 553
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000244005 | NFS1 cysteine desulfurase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 36 | 16 | 40 |
| disruptive | 15 | 37 | 19 | 68 |
| missense | 15 | 35 | 17 | 55 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 88 | 24 | 34 |
| disruptive | 26 | 90 | 43 | 123 |
| missense | 19 | 74 | 36 | 87 |
PlasmoDB Total SNPs: 115
Non-coding: 78 | Synonymous: 18 | Nonsynonymous: 19 | Stop Codon: 0
Protein Length: 553 | Molecular Weight (kDa): 63.209
UniProt ID(s): A0A5J6C6C1, A0A5J6C6M9, A0A5J6C6N9, A0A5J6C6R3, A0A5J6C6T6, A0A5J6C6U8, A0A5J6C6V4, A0A5J6C715, A0A5J6C733, A0A5J6C789, A0A5J6C7A3, A0A5J6C7J0, A0A5J6C7K0, A0A5J6C7K1, A0A5J6C7L1, A0A5J6C855, A0A5J6C887, A0A5J6C896, A0A5J6C8B8, A0A5J6C8C2, A0A5J6C8D6, A0A5J6C8W8, A0A5J6C917, A0A5J6C964, A0A5J6CAJ4, Q8IBI5
PDB ID(s): None
Isoelectric Point: 8.75
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000192 | Aminotransferase class V domain |
| InterPro | IPR010240 | Cysteine desulfurase IscS |
| InterPro | IPR015424 | Pyridoxal phosphate-dependent transferase |
| InterPro | IPR020578 | Aminotransferase class-V, pyridoxal-phosphate binding site |
| PFam | PF00266 | Aminotransferase class V domain |
| Superfamily | SSF53383 | Pyridoxal phosphate-dependent transferase |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12946854 | Targeting GFP to the malarial mitochondrion. | Sato S, Rangachari K, Wilson RJ | 10.1016/s0166-6851(03)00166-x |
| 24086138 | The suf iron-sulfur cluster synthesis pathway is required for apicoplastmaintenance in malaria parasites. | Gisselberg JE, Dellibovi-Ragheb TA, ..., Prigge ST | 10.1371/journal.ppat.1003655 |
| 34032321 | [Fe-S] biogenesis and unusual assembly of the ISC scaffold complex in thePlasmodium falciparum mitochondrion. | Mohammad Sadik, Mohammad Afsar, Ramachandran R, Habib S | 10.1111/mmi.14735 |
| 34494883 | A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. | van Esveld SL, Meerstein-Kessel L, ..., Huynen MA | 10.1128/mSphere.00614-21 |
| 34612205 | Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesisfrom fatty acid synthesis in malaria parasites | Falekun S, Sepulveda J, ..., Sigala PA | 10.7554/eLife.71636 |
| 36773733 | Essential mitochondrial role in iron-sulfur cluster assembly of the cytoplasmicisopropylmalate isomerase Leu1 in Saccharomyces cerevisiae | Pandey AK, Pain J, ..., Pain D | 10.1016/j.mito.2023.02.006 |