Genome location: Pf3D7_11_v3:1,500,670..1,514,612(-)
Genome classification: Core
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:
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)
Zhang Phenotype: Mutable in CDS
MIS: 0.954 | MFS: -2.882 | #Insertions: 1
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0910300)
RMgmDB ABS Phenotype: Not tested (Pb ortholog: PY17X_0911700)
Modification: Tagged | RMgm-4822
More info: PhenoPlasm Link
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
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 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 |
| 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 |