Genome location: Pf3D7_12_v3:439,389..443,398(+)
Genome classification: Core
Product Description: cGMP-specific 3',5'-cyclic phosphodiesterase alpha
SignalP Peptide: N/A
# Transmembrane Domains: 6
EC Numbers: 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0016020 | membrane |
| Function | GO:0047555 | 3',5'-cyclic-GMP phosphodiesterase activity |
| Function | GO:0004114 | 3',5'-cyclic-nucleotide phosphodiesterase activity |
| Function | GO:0030553 | cGMP binding |
| Process | GO:0046069 | cGMP catabolic process |
| 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 | expressed | N/A | N/A |
| Ring | not expressed | nd | nd |
| Trophozoite | possibly expressed | nd | nd |
| Schizont | expressed | nd | nd |
| Gametocyte | possibly expressed | nd | nd |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1209500.2
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: -2.516 | #Insertions: 4
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0607900)
Modification: Disrupted | RMgm-5384
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5V4
"Best" AlphaFill ligand hit: R75 (benzbromarone, Local RMSD=0.49) with 8K4H (Global RMSD=1.65)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P27815 | cAMP-specific 3',5'-cyclic phosphodiesterase 4A | Homo sapiens | OrthoDB | L-869298L-869299(R,S)-RolipramV11294... |
| Q08493 | cAMP-specific 3',5'-cyclic phosphodiesterase 4C | OrthoDB | L-869298L-869299BDBM302435US9598421, Example 2... | |
| Q13946 | High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A | Homo sapiens | OrthoDB | US8637528, OM69US8637528, OM056US8637528, OM955CHEMBL363097... |
| Q08499 | cAMP-specific 3',5'-cyclic phosphodiesterase 4D | OrthoDB | L-869298L-869299(R,S)-RolipramV11294... | |
| P14646 | cAMP-specific 3',5'-cyclic phosphodiesterase 4B | Rattus | OrthoDB | CDP 840CDP 840CilomilastCilomilast... |
| Q01064 | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B | Homo sapiens | OrthoDB | Sildenafil#VardenafilUS11634416, Example 1US11634416, Example 2... |
| P54750 | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A | OrthoDB | US9073936, 1US9073936, 2US9073936, 3US9073936, 4... | |
| Q07343 | cAMP-specific 3',5'-cyclic phosphodiesterase 4B | OrthoDB | L-869298L-869299(R,S)-RolipramV11294... | |
| P70453 | High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A | Mus musculus | OrthoDB | CHEMBL2171421 |
| Q8VBU5 | Phosphodiesterase/cAMP-specific 3',5'-cyclic phosphodiesterase 4A/cAMP-specific 3',5'-cyclic phosphodiesterase 4C/cAMP-specific 3',5'-cyclic phosphodiesterase 4D | OrthoDB | US8901315, 10US8901315, 11US8901315, 12US8901315, 14... | |
| Q9NP56 | cAMP-specific 3',5'-cyclic phosphodiesterase 7B | Homo sapiens | OrthoDB | FilaminastPiclamilastVardenafilUS8637528, OM69... |
| Q63421 | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B/Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C/Phosphodiesterase | OrthoDB | CHEMBL51814CHEMBL311616CHEMBL73152CHEMBL423125... | |
| Q01063 | cAMP-specific 3',5'-cyclic phosphodiesterase 4D | OrthoDB | CHEMBL4209111CHEMBL22898CHEMBL21839CHEMBL21463... | |
| Q14123 | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C | OrthoDB | US8741907, 3US8741907, 3US11634416, Example 1US11634416, Example 2... |
Ortholog Group (OrthoMCL): OG6_105168
Most Similar Human Ortholog: D6R9W0
TM-align score: 0.41 | RMSD: 5.09
Seq Identity: 0.07 | Length: 86 / 954
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000073417 | phosphodiesterase 8A |
| ENSG00000113231 | phosphodiesterase 8B |
| ENSG00000284762 | phosphodiesterase 8B |
Protein Length: 954 | Molecular Weight (kDa): 115.412
PDB ID(s): None
Isoelectric Point: 8.63
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR002073 | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain |
| InterPro | IPR003607 | HD/PDEase domain |
| InterPro | IPR023088 | 3'5'-cyclic nucleotide phosphodiesterase |
| PFam | PF00233 | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain |
| Superfamily | SSF109604 | N/A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 55 | 25 | 51 |
| disruptive | 27 | 74 | 42 | 133 |
| missense | 24 | 73 | 42 | 125 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 20 | 86 | 46 | 47 |
| disruptive | 44 | 166 | 87 | 213 |
| missense | 39 | 138 | 75 | 162 |
PlasmoDB Total SNPs: 114
Non-coding: 46 | Synonymous: 41 | Nonsynonymous: 27 | 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 |