PDED_PLAF7
ID PDED_PLAF7 Reviewed; 815 AA.
AC Q8IKD3; B3FEM8;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase delta {ECO:0000305};
DE Short=PfPDEdelta {ECO:0000303|PubMed:18452584};
DE EC=3.1.4.35 {ECO:0000305|PubMed:18452584};
GN Name=PDEdelta {ECO:0000303|PubMed:18590734};
GN Synonyms=PDE4 {ECO:0000303|PubMed:18590734};
GN ORFNames=PF3D7_1470500 {ECO:0000312|EMBL:CZU00402.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|EMBL:ABS50260.1};
RN [1] {ECO:0000312|EMBL:ABS50260.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=3D7 {ECO:0000312|EMBL:ABS50260.1};
RX PubMed=18590734; DOI=10.1016/j.ijpara.2008.05.016;
RA Wentzinger L., Bopp S., Tenor H., Klar J., Brun R., Beck H.P., Seebeck T.;
RT "Cyclic nucleotide-specific phosphodiesterases of Plasmodium falciparum:
RT PfPDEalpha, a non-essential cGMP-specific PDE that is an integral membrane
RT protein.";
RL Int. J. Parasitol. 38:1625-1637(2008).
RN [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18452584; DOI=10.1111/j.1365-2958.2008.06267.x;
RA Taylor C.J., McRobert L., Baker D.A.;
RT "Disruption of a Plasmodium falciparum cyclic nucleotide phosphodiesterase
RT gene causes aberrant gametogenesis.";
RL Mol. Microbiol. 69:110-118(2008).
CC -!- FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a
CC key regulator of many important physiological processes
CC (PubMed:18452584). Probably by regulating cGMP levels, required for
CC activation of gametogenesis (PubMed:18452584).
CC {ECO:0000269|PubMed:18452584}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; EC=3.1.4.35;
CC Evidence={ECO:0000305|PubMed:18452584};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000255|RuleBase:RU363067};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions, while site 2 has a preference for
CC magnesium and/or manganese ions. {ECO:0000255|RuleBase:RU363067};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC 3',5'-cyclic GMP: step 1/1. {ECO:0000269|PubMed:18452584}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage, probably
CC in gametocytes. {ECO:0000269|PubMed:18452584,
CC ECO:0000269|PubMed:18590734}.
CC -!- DISRUPTION PHENOTYPE: Impaired gametogenesis (PubMed:18452584).
CC Gametocytes are morphologically normal up to and including stage V of
CC development; however, gametocytes fail to round up upon stimulation of
CC gametogenesis with xanthurenic acid and levels of exflagellation are
CC severely reduced (PubMed:18452584). Higher levels of intracellular cGMP
CC in stages III to V gametocytes (PubMed:18452584).
CC {ECO:0000269|PubMed:18452584}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000255|RuleBase:RU363067}.
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DR EMBL; EF673788; ABS50260.1; -; mRNA.
DR EMBL; LN999946; CZU00402.1; -; Genomic_DNA.
DR RefSeq; XP_001348846.2; XM_001348810.2.
DR AlphaFoldDB; Q8IKD3; -.
DR SMR; Q8IKD3; -.
DR STRING; 5833.PF14_0672; -.
DR PRIDE; Q8IKD3; -.
DR EnsemblProtists; CZU00402; CZU00402; PF3D7_1470500.
DR GeneID; 812254; -.
DR KEGG; pfa:PF3D7_1470500; -.
DR VEuPathDB; PlasmoDB:PF3D7_1470500; -.
DR HOGENOM; CLU_346656_0_0_1; -.
DR InParanoid; Q8IKD3; -.
DR OMA; FEYVDIF; -.
DR PhylomeDB; Q8IKD3; -.
DR Reactome; R-PFA-180024; DARPP-32 events.
DR Reactome; R-PFA-418555; G alpha (s) signalling events.
DR UniPathway; UPA00763; UER00748.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IMP:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISS:GeneDB.
DR GO; GO:0030552; F:cAMP binding; ISS:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IMP:UniProtKB.
DR GO; GO:0009187; P:cyclic nucleotide metabolic process; ISS:GeneDB.
DR GO; GO:0007276; P:gamete generation; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW cGMP; Glycoprotein; Hydrolase; Membrane; Metal-binding; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..815
FT /note="cGMP-specific 3',5'-cyclic phosphodiesterase delta"
FT /id="PRO_0000452650"
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..86
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..160
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 182..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..210
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..815
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 384..762
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT ACT_SITE 459
FT /note="Proton donor"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-1"
FT BINDING 459..463
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 463
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-3"
FT BINDING 499
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-3"
FT BINDING 500
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 500
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-3"
FT BINDING 500
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-3"
FT BINDING 616
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 616
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-3"
FT BINDING 715
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 815 AA; 97169 MW; 9A5BA346F8EE9D0C CRC64;
MNEYNNDNME QEKEKKKEEQ KYKNIIKKEY FIFPRLYDKN KEIEYNKLRI HNIKEYICIH
LTISLFIILI ECFVFSFNLN IKDTTYVEIC VVIFSILNCL MHIVVLIKMY FFTSESVYTK
GVFIGYIVLN QVFQFLSLYF FTKRNEQSKN DIAHLKYYDN SFNLYVHFFV DSVFILCLPA
LSFFLSVLFM MMFLCLNILL INMIKFNKTN YGSDIYHICL LSVVLLMFLI LRYMMEERNR
LLFFFIKDMM FDNYKKWYSD YIGAHYDKDK DSTTINGDNN KYEKEKCEDY KFLFSNKCIL
FHDFTLNACY KDYYSMICFL NKLLKSCNIK EDMSSNTSVN INGDTYQNMN FHDNINSNIP
KNYNSFYEEL KKNLNESDIL TIAYEVEVLK NIKKINCDEI GKNWDYSFID SEYGKSTLVI
LEVGYHLISP YIENNENKKK KLQLFLLLIN SMYFPNPYHN ANHGATVCHL SKCLAHITDY
DSYLNNTYMI CYLIASIAHD VGHPGKTNSY LSETNHILSI RYNDMSILEN YHCSITFSIL
QLIGFDFLIN NEDTKLVEKN NYTNMRKFII ELIISTDMKL HFEYVDIFKK RKKSQNFDIS
DTDAINLGTI NIKLADIGHT CLKWKDHAKW TMLVSEEFFS QKRVEELHKN KNIDPLNFSN
FGKEDNIDEG MIFNYENIYI NYINNINNIN TYDYSYIKLN FIHHHDFVKS IPSTQVYFFE
IIVMPLIKEL QSMEKSKKEI TQKVLHNLNI NLQTWRLIEK NINLFYNTEK MTGTDYYKNL
EKQKLLRGIR LLDIAEEDVI SLTKNFKEEI KHGKL
