Genome location: Pf3D7_14_v3:2,881,612..2,886,576(+)
Genome classification: Core
Product Description: cGMP-specific 3',5'-cyclic phosphodiesterase delta
SignalP Peptide: N/A
# Transmembrane Domains: 6
EC Numbers: 3.1.4.- (Phosphoric diester hydrolases.);3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase);3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0016020 | membrane |
| Function | GO:0004115 | 3',5'-cyclic-AMP phosphodiesterase activity |
| Function | GO:0047555 | 3',5'-cyclic-GMP phosphodiesterase activity |
| Function | GO:0004114 | 3',5'-cyclic-nucleotide phosphodiesterase activity |
| Function | GO:0030552 | cAMP binding |
| Process | GO:0046068 | cGMP metabolic process |
| Process | GO:0009187 | cyclic nucleotide metabolic 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 | not expressed | N/A | N/A |
| Ring | not expressed | 0.08 | 0.96 |
| Trophozoite | not expressed | 0.26 | 0.84 |
| Schizont | not expressed | 0.20 | 0.87 |
| Gametocyte | expressed | 1.03 | 0.48 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1470500
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: -0.175 | #Insertions: 2
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1333700)
Modification: Disrupted | RMgm-5384
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKD3
"Best" AlphaFill ligand hit: B3P (2-[3-(2-hydroxy-1,1-dihydroxymethyl-ethylamino)-propylamino]-2-hydroxymethyl-propane-1,3-diol, Local RMSD=0.15) with 3KKT (Global RMSD=4.40)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.1.4.- | Ex: 3',5'-cyclic-nucleotide phosphodiesterase | KFATPADPCoAFADUDPAMPGTPCTPUTPCMPUMP... |
| 3.1.4.17 | 3',5'-cyclic-nucleotide phosphodiesterase | ATPADPFADAMPGTPGDPGMPNaFNAD+NADHEDTAcAMP... |
| 3.1.4.35 | 3',5'-cyclic-GMP phosphodiesterase | ATPGTPEDTAcAMPcGMPCHAPSE4021CP461T0156Evo48T-1032histone... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q13370 | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B | Homo sapiens | OrthoDB | Papaverine6,7-Dimethoxy-4-pyrrolidylquinazoline 66,7-Dimethoxy-4-pyrrolidylquinazoline 76,7-Dimethoxy-4-pyrrolidylquinazoline 8... |
| E1BN64 | Phosphodiesterase | Bos taurus | OrthoDB | CHEMBL306666CHEMBL308249CHEMBL304389CHEMBL431377... |
| O77746 | cGMP-specific 3',5'-cyclic phosphodiesterase | Canis lupus dingo | OrthoDB | Sildenafil#CHEMBL77795CHEMBL539778CHEMBL77971... |
| Q8QZV1 | High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A | OrthoDB | US8822448, 147US8822447, 106US8822447, 107US8822448, 1... | |
| Q9XSW7 | Phosphodiesterase | Sus scrofa | OrthoDB | CHEMBL302299PapaverineMilrinone |
| O70628 | High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A | OrthoDB | US8822479, 37-1CHEMBL5198935PF-04447943 | |
| Q28263 | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha | Canis familiaris | OrthoDB | UK-371800CHEMBL460294CHEMBL444157CHEMBL514435... |
| P51160 | O43924/P16499/P18545/P35913/P51160/Q13956 | OrthoDB | CHEMBL438451CHEMBL213113CHEMBL377563CHEMBL213219... | |
| O00408 | cGMP-dependent 3',5'-cyclic phosphodiesterase | OrthoDB | US8829010, 35US8829010, 58VardenafilUS8598155, 10... | |
| O76074 | cGMP-specific 3',5'-cyclic phosphodiesterase | Homo sapiens | OrthoDB | Sildenafil#CHEMBL209157Sildenafil 5-methyl ketone analogue 2Sildenafil 5-methyl ketone analogue 9... |
| P11541 | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha | OrthoDB | US9359371, 3US9359371, 11US9359371, 38US9359371, 46... | |
| B3VTJ2 | Phosphodiesterase | OrthoDB | US10195201, Example 1US10195201, Example 1US10195201, Example 2US10195201, Example 3... | |
| Q01062 | cGMP-dependent 3',5'-cyclic phosphodiesterase | Rattus norvegicus | OrthoDB | CHEMBL100779CHEMBL4074744US8598155, 2 |
| Q9Y233 | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | Homo sapiens | OrthoDB | Sildenafil#VardenafilBC11-38-2BC11-38-4... |
| Q14432 | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A | Homo sapiens | OrthoDB | Papaverine6,7-Dimethoxy-4-pyrrolidylquinazoline 26,7-Dimethoxy-4-pyrrolidylquinazoline 36,7-Dimethoxy-4-pyrrolidylquinazoline 4... |
| O60658 | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A | Homo sapiens | OrthoDB | CilomilastDipyridamineUS8846654, 11US8846654, 251... |
| C4PBI8 | Phosphodiesterase | OrthoDB | US10376504, Example 1-7US10376504, Example 1-8US10376504, Example 1-9US10376504, Example 1-10... | |
| O95263 | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B | Homo sapiens | OrthoDB | CHEMBL2326941CHEMBL1780094CHEMBL1779987CHEMBL1780096... |
| Q9HCR9 | Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A | OrthoDB | PiclamilastSildenafil#VardenafilGF 196960... | |
| O76083 | High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A | Homo sapiens | OrthoDB | Sildenafil#VardenafilUS8623901, 219US8623901, 220... |
| O54735 | cGMP-specific 3',5'-cyclic phosphodiesterase | Rattus norvegicus | OrthoDB | CHEMBL77651CHEMBL77651KURAIDINKURARINOL... |
| Q28156 | cGMP-specific 3',5'-cyclic phosphodiesterase | Bos taurus | OrthoDB | TrequinsinCHEMBL140173CHEMBL305237CHEMBL278644... |
| Q9QYJ6 | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | Rattus norvegicus | OrthoDB | 6,7-Dimethoxy-4-pyrrolidylquinazoline 26,7-Dimethoxy-4-pyrrolidylquinazoline 36,7-Dimethoxy-4-pyrrolidylquinazoline 46,7-Dimethoxy-4-pyrrolidylquinazoline 5... |
| Q8CA95 | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | Mus musculus | OrthoDB | CHEMBL3315046CHEMBL3315045CHEMBL3315044CHEMBL3315042... |
| P16499 | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha/beta | Homo sapiens | OrthoDB | US10899756, Compound DUS10899756, Compound ECHEMBL4062273US11180503, Example 6... |
Protein Length: 815 | Molecular Weight (kDa): 97.169
UniProt ID(s): Q8IKD3
PDB ID(s): None
Isoelectric Point: 6.98
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 |
| InterPro | IPR023174 | 3'5'-cyclic nucleotide phosphodiesterase, conserved site |
| 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 | 5 | 49 | 24 | 54 |
| disruptive | 11 | 31 | 38 | 86 |
| missense | 11 | 30 | 37 | 72 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 90 | 41 | 60 |
| disruptive | 18 | 101 | 90 | 155 |
| missense | 16 | 81 | 71 | 109 |
PlasmoDB Total SNPs: 345
Non-coding: 283 | Synonymous: 49 | Nonsynonymous: 12 | Stop Codon: 1
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 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 |
| 18590734 | Cyclic nucleotide-specific phosphodiesterases of Plasmodium falciparum:PfPDEalpha, a non-essential cGMP-specific PDE that is an integral membraneprotein. | Wentzinger L, Bopp S, ..., Seebeck T | 10.1016/j.ijpara.2008.05.016 |
| 34171456 | Tadalafil impacts the mechanical properties of Plasmodium falciparumgametocyte-infected erythrocytes. | N'Dri ME, Royer L, Lavazec C | 10.1016/j.molbiopara.2021.111392 |