About Gene List

PF3D7_1321600 (PDEgamma)

Genome location: Pf3D7_13_v3:897,716..901,044(+)

Genome classification: Core

Function and Localization

Product Description: cGMP-specific 3',5'-cyclic phosphodiesterase gamma, putative

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:0005783 endoplasmic reticulum
Component GO:0016020 membrane
Function GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
Function GO:0004117 calmodulin-dependent cyclic-nucleotide phosphodiesterase activity
Process GO:0046068 cGMP metabolic process
Process GO:0071976 cell gliding
Process GO:0044409 entry into host
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 0.02 0.99
Trophozoite not expressed 0.02 0.99
Schizont not expressed 0.08 0.95
Gametocyte possibly expressed 0.21 0.88

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1321600

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: 1 | MFS: -1.732 | #Insertions: 6

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PbANKA_1419900)

Modification: Disrupted | RMgm-5381

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: B3FEM7

"Best" AlphaFill ligand hit: B3P (2-[3-(2-hydroxy-1,1-dihydroxymethyl-ethylamino)-propylamino]-2-hydroxymethyl-propane-1,3-diol, Local RMSD=0.30) with 3KKT (Global RMSD=7.16)

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...

Orthology Information

Ortholog Group (OrthoMCL): OG6_106516

Most Similar Human Ortholog: Q14432

TM-align score: 0.46 | RMSD: 4.41

Seq Identity: 0.24 | Length: 398 / 769

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000152270 phosphodiesterase 3B
ENSG00000172572 phosphodiesterase 3A

Protein Information

Protein Length: 769 | Molecular Weight (kDa): 91.68

UniProt ID(s): B3FEM7

PDB ID(s): None

Isoelectric Point: 8.98

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

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 6 40 20 39
disruptive 7 41 26 84
missense 5 39 25 74

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 11 70 28 47
disruptive 15 101 59 137
missense 7 83 48 90

PlasmoDB Total SNPs: 157

Non-coding: 131 | Synonymous: 19 | Nonsynonymous: 6 | Stop Codon: 1

Associated Publications

PMID Title Authors DOI/Link
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
25784701 Cyclic GMP balance is critical for malaria parasite transmission from themosquito to the mammalian host. Lakshmanan V, Fishbaugher ME, ..., Kappe SH 10.1128/mBio.02330-14