About Gene List

PF3D7_1457000 (SPP)

Genome location: Pf3D7_14_v3:2,336,071..2,339,501(-)

Genome classification: Core

Function and Localization

Product Description: signal peptide peptidase

SignalP Peptide: N/A

# Transmembrane Domains: 8

EC Numbers: 3.4.21.89 (Signal peptidase I)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0009986 cell surface
Component GO:0005783 endoplasmic reticulum
Component GO:0071458 integral component of cytoplasmic side of endoplasmic reticulum membrane
Component GO:0071556 integral component of lumenal side of endoplasmic reticulum membrane
Component GO:0020009 microneme
Function GO:0042500 aspartic endopeptidase activity, intramembrane cleaving
Function GO:0008233 peptidase activity
Function GO:0042803 protein homodimerization activity
Process GO:0033619 membrane protein proteolysis
Process GO:0009410 response to xenobiotic stimulus
Process GO:0006465 signal peptide processing

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 0.52 0.77
Trophozoite expressed 1.04 0.47
Schizont expressed 0.77 0.56
Gametocyte expressed 0.81 0.57

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1457000

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.767 | MFS: -2.528 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1320700)

  • Relative Growth Rate: 0.06 ± 0.12
  • Confidence: 5.58

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IKQ9

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.4.21.89 Signal peptidase I NEMSDSEDTAMG132cholateantipainL685,458rifampicinBAL0019193arylomycinlactacystindeoxycholate...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_102328

Most Similar Human Ortholog: A0A0S2Z6F0

TM-align score: 0.84 | RMSD: 2.20

Seq Identity: 0.38 | Length: 307 / 412

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000101294 histocompatibility minor 13

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 22 13 30
disruptive 4 13 4 33
missense 4 13 4 28

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 6 34 33 25
disruptive 5 46 19 92
missense 4 36 16 65

PlasmoDB Total SNPs: 240

Non-coding: 218 | Synonymous: 17 | Nonsynonymous: 5 | Stop Codon: 0

Protein Information

Protein Length: 412 | Molecular Weight (kDa): 47.579

UniProt ID(s): C0KWU7, C0KWV2, Q8IKQ9

PDB ID(s): None

Isoelectric Point: 9.06

Protein Domain Annotations:

Source Family ID Description
InterPro IPR006639 Presenilin/signal peptide peptidase
InterPro IPR007369 Peptidase A22B, signal peptide peptidase
PFam PF04258 Peptidase A22B, signal peptide peptidase
Superfamily N/A N/A

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
18160114 A Presenilin-like protease associated with Plasmodium falciparum micronemes isinvolved in erythrocyte invasion. Li X, Chen H, Oh SS, Chishti AH 10.1016/j.molbiopara.2007.11.007
22844982 Malaria parasite signal peptide peptidase is an ER-resident protease required forgrowth but not for invasion. Marapana DS, Wilson DW, ..., Baum J 10.1111/j.1600-0854.2012.01402.x
25017910 Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein101 (HSP101). Implications for gametocytogenesis. Baldwin M, Russo C, Li X, Chishti AH 10.1016/j.bbrc.2014.07.013
27128092 Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. Swearingen KE, Lindner SE, ..., Sinnis P 10.1371/journal.ppat.1005606
29187532 Characterization of SPP inhibitors suppressing propagation of HCV and protozoa. Hirano J, Okamoto T, ..., Matsuura Y 10.1073/pnas.1712484114
38430291 Characterization and Biological Activities of the Ulvan Polysaccharide-RichFraction Obtained from Ulva rigida and Ulva pseudorotundata and Their Potentialfor Pharmaceutical Application Favero Massocato T, Robles-Carnero V, ..., Lopez Figueroa FD 10.1007/s10126-024-10299-8