About Gene List

PF3D7_1138400 (GCalpha)

Genome location: Pf3D7_11_v3:1,500,670..1,514,612(-)

Genome classification: Core

Function and Localization

Product Description: guanylyl cyclase alpha

SignalP Peptide: N/A

# Transmembrane Domains: 19

EC Numbers: 4.6.1.2 (Guanylate cyclase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0031410 cytoplasmic vesicle
Component GO:0005887 integral component of plasma membrane
Component GO:0005886 plasma membrane
Function GO:0140326 ATPase-coupled intramembrane lipid transporter activity
Function GO:0004383 guanylate cyclase activity
Function GO:0005515 protein binding
Process GO:0006182 cGMP biosynthetic process
Process GO:0035891 exit from host cell
Process GO:0045332 phospholipid translocation
Process GO:0007165 signal transduction

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 0.20 0.90
Trophozoite expressed 0.64 0.68
Schizont expressed 1.41 0.44
Gametocyte expressed 0.64 0.67

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1138400

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: Mutable in CDS

MIS: 0.954 | MFS: -2.882 | #Insertions: 1

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0910300)

  • Relative Growth Rate: 0.36 ± 0.21
  • Confidence: 4.48

RMgmDB ABS Phenotype: Not tested (Pb ortholog: PY17X_0911700)

Modification: Tagged | RMgm-4822

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: N/A

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
4.6.1.2 guanylate cyclase BRENDA SOAP query unsuccessful

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_119479

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 38 254 156 334
disruptive 133 529 288 644
missense 77 462 266 565

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 66 577 208 349
disruptive 246 1041 436 952
missense 151 869 376 705

PlasmoDB Total SNPs: 417

Non-coding: 84 | Synonymous: 185 | Nonsynonymous: 148 | Stop Codon: 0

Protein Information

Protein Length: 4226 | Molecular Weight (kDa): 496.021

UniProt ID(s): O96856, Q8IHY1, Q9N9H5

PDB ID(s): None

Isoelectric Point: 9.23

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001054 Adenylyl cyclase class-3/4/guanylyl cyclase
InterPro IPR006539 P-type ATPase, subfamily IV
InterPro IPR008250 P-type ATPase, A domain superfamily
InterPro IPR018303 P-type ATPase, phosphorylation site
InterPro IPR023298 P-type ATPase, transmembrane domain superfamily
InterPro IPR029787 Nucleotide cyclase
InterPro IPR032630 P-type ATPase, C-terminal
InterPro IPR036412 HAD-like superfamily
PFam PF00122 Adenylyl cyclase class-3/4/guanylyl cyclase
PFam PF00211 P-type ATPase, C-terminal
PFam PF16212
Superfamily SSF55073 Nucleotide cyclase
Superfamily SSF56784 HAD-like superfamily
Superfamily SSF81653 P-type ATPase, A domain superfamily
Superfamily SSF81665 P-type ATPase, transmembrane domain superfamily

Associated Publications

PMID Title Authors DOI/Link
10747978 Guanylyl cyclase activity associated with putative bifunctional integral membraneproteins in Plasmodium falciparum. Carucci DJ, Witney AA, ..., Baker DA 10.1074/jbc.M001021200
11152613 Predicting transmembrane protein topology with a hidden Markov model: applicationto complete genomes. Krogh A, Larsson B, von Heijne G, Sonnhammer EL 10.1006/jmbi.2000.4315
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
18452584 Disruption of a Plasmodium falciparum cyclic nucleotide phosphodiesterase genecauses aberrant gametogenesis. Taylor CJ, McRobert L, Baker DA 10.1111/j.1365-2958.2008.06267.x
33500341 Plasmodium falciparum Guanylyl Cyclase-Alpha and the Activity of Its Appended P4-ATPase Domain Are Essential for c GMP Synthesis and Blood-Stage Egress Nofal SD, Patel A, ..., Baker DA 10.1128/mBio.02694-20
35862778 CDC50 Orthologues in Plasmodium falciparum Have Distinct Roles in MerozoiteEgress and Trophozoite Maturation. Patel A, Nofal SD, Blackman MJ, Baker DA 10.1128/mbio.01635-22
32669539 Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes Paul AS, Miliu A, ..., Duraisingh MT 10.1038/s41467-020-17306-1
37327340 A Plasmodium membrane receptor platform integrates cues for egress and invasionin blood forms and activation of transmission stages Kuehnel RM, Ganga E, ..., Brochet M 10.1126/sciadv.adf2161
36768882 Characterizing the Specific Recognition of Xanthurenic Acid by GEP1 and GEP1-GCalphaInteractions in cGMP Signaling Pathway in Gametogenesis of Malaria Parasites Zhu C, Liang X, ..., Luo S 10.3390/ijms24032561
32273496 An intracellular membrane protein GEP1 regulates xanthurenic acid inducedgametogenesis of malaria parasites Jiang Y, Wei J, ..., Yuan J 10.1038/s41467-020-15479-3