PDEG_PLAYE
ID PDEG_PLAYE Reviewed; 782 AA.
AC A0A077YBL0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase gamma {ECO:0000305};
DE EC=3.1.4.35 {ECO:0000305|PubMed:25784701};
GN Name=PDEgamma {ECO:0000303|PubMed:25784701};
GN ORFNames=PY17X_1421600 {ECO:0000312|EMBL:VTZ81530.1};
OS Plasmodium yoelii.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5861 {ECO:0000312|Proteomes:UP000072874};
RN [1] {ECO:0000312|Proteomes:UP000072874}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17X {ECO:0000312|Proteomes:UP000072874};
RX PubMed=25359557; DOI=10.1186/s12915-014-0086-0;
RA Otto T.D., Bohme U., Jackson A.P., Hunt M., Franke-Fayard B.,
RA Hoeijmakers W.A., Religa A.A., Robertson L., Sanders M., Ogun S.A.,
RA Cunningham D., Erhart A., Billker O., Khan S.M., Stunnenberg H.G.,
RA Langhorne J., Holder A.A., Waters A.P., Newbold C.I., Pain A., Berriman M.,
RA Janse C.J.;
RT "A comprehensive evaluation of rodent malaria parasite genomes and gene
RT expression.";
RL BMC Biol. 12:86-86(2014).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=17XNL {ECO:0000269|PubMed:25784701};
RX PubMed=25784701; DOI=10.1128/mbio.02330-14;
RA Lakshmanan V., Fishbaugher M.E., Morrison B., Baldwin M., Macarulay M.,
RA Vaughan A.M., Mikolajczak S.A., Kappe S.H.;
RT "Cyclic GMP balance is critical for malaria parasite transmission from the
RT mosquito to the mammalian host.";
RL MBio 6:e02330-e02330(2015).
CC -!- FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a
CC key regulator of many important physiological processes (Probable).
CC Probably by regulating cGMP levels, required for sporozoite motility
CC and invasion of the mosquito salivary glands (PubMed:25784701).
CC {ECO:0000269|PubMed:25784701, ECO:0000305|PubMed:25784701}.
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:25784701};
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:25784701}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25784701}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Intracellular localization in blood stage forms and
CC in sporozoites (PubMed:25784701). Partially, localizes to the
CC endoplasmic reticulum in blood stage forms (PubMed:25784701).
CC {ECO:0000269|PubMed:25784701}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage
CC (PubMed:25784701). In the mosquito vector, expressed in oocyst
CC sporozoites, and salivary gland sporozoites (PubMed:25784701).
CC {ECO:0000269|PubMed:25784701}.
CC -!- DISRUPTION PHENOTYPE: During infection of Swiss Webster mice, lack of
CC PDEgamma reduces peak blood stage parasitemia (PubMed:25784701). In the
CC mosquito, development of oocyst sporozoites is not affected
CC (PubMed:25784701). However, sporozoites released from the oocyst have
CC higher cGMP levels, are immotile and fail to invade the salivary glands
CC and, thus, parasite transmission to the mammalian host is impaired
CC (PubMed:25784701). In addition, in sporozoites, mRNA levels of PDEbeta
CC and PDEdelta are up-regulated and several transcripts encoding proteins
CC involved in sporozoite invasion of mosquito salivary glands and
CC sporozoite infectivity such as TRAP and CSP are down-regulated
CC (PubMed:25784701). {ECO:0000269|PubMed:25784701}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000255|RuleBase:RU363067}.
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DR EMBL; LK934642; CDU20569.1; -; Genomic_DNA.
DR EMBL; LM993668; VTZ81530.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A077YBL0; -.
DR SMR; A0A077YBL0; -.
DR EnsemblProtists; CDU20569; CDU20569; PYYM_1423400.
DR EnsemblProtists; CDZ14196; CDZ14196; PY17X_1421600.
DR VEuPathDB; PlasmoDB:PY01856; -.
DR VEuPathDB; PlasmoDB:PY01857; -.
DR VEuPathDB; PlasmoDB:PY17X_1421600; -.
DR VEuPathDB; PlasmoDB:PYYM_1423400; -.
DR PhylomeDB; A0A077YBL0; -.
DR UniPathway; UPA00763; UER00748.
DR Proteomes; UP000072874; Chromosome 14.
DR Proteomes; UP000072904; Chromosome 14.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
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 SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW cGMP; Endoplasmic reticulum; Hydrolase; Membrane; Metal-binding;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..782
FT /note="cGMP-specific 3',5'-cyclic phosphodiesterase gamma"
FT /id="PRO_0000452649"
FT TOPO_DOM 1..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 70..90
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..97
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 98..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..181
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..239
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..782
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 423..751
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 376..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 504
FT /note="Proton donor"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-1"
FT BINDING 504..508
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 508
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 544
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 545
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 545
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 545
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 654
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 654
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 706
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
SQ SEQUENCE 782 AA; 92307 MW; B49400D46CC5336D CRC64;
MKHMFKNILF HKKGKHDKND AIKKAFSLFS VPSNENERII KFWPLKFKEK DEETLYIIKL
CDNMYSKKYV ILVSHLISLL LMYSVCLIVG NINDLFSVLK LTYILLHTFT AINIILILTL
HATHYVEMFK SIKGEIFIFY IMMIFVIWCS WLFILFNNIK DLLPIVVNVN NFLYATYANN
KINIVLGFFA YLPIFYLITI IPCRICYSCA FDILFFIMKV AIFSVYYLIT MKSYILTDNI
FMIISALVGS LFIFVIRYII EIQRRLSFHN WNKQTKQIIK LKKTLKEEKQ KLSTTNIEEI
YNLINDSIGN YYNENKKQKE TDWSIVNNLE KILNILKEDN LFSPDLKTIN KKNYNHIYGY
IMDLKKQKEI INDKIGSKEE PEAESESECV DESKEGSQIE SIFESISDVK QKKKSDLAYT
SSYEEKENEI LKYDFNMNMD KENISIDIWN TKFLDRKSPN YDAFIKIGYI LLNKYYISNQ
NISVKILYSL LYEMKKGYND VPYHNSIHAA MVTKHCSILI TSLDTVNILK DNEMAAFLIS
ALGHDIGHFG RTNMFLKNCS NFLRIIYNDK SILENYHCSY LFNILSKEEH NIFKKEDLKT
LTNLRQLIIE VILATDMSKH IKILAQFRIK SIKIKSYIEK NIILCLKMII KAADLSHNCV
DWSEHYLWVK RLVNEFYSEG DDLLERGFEL NPLFDRKAHN NFIQIQRTFL RELVLPLISS
LKTLDTSTIT QLMLSHVKRN YSKWTKIEKD ETKKEKYLNE LLTDVPNSWK IVYAPNLNIY
KL
