PDEA_PLAF7
ID PDEA_PLAF7 Reviewed; 954 AA.
AC Q8I5V4; B3FEM4; B3FEM5; Q2V2M6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase alpha {ECO:0000305};
DE Short=PfPDE1 {ECO:0000303|PubMed:16038615};
DE Short=PfPDEalpha {ECO:0000303|PubMed:18590734};
DE EC=3.1.4.35 {ECO:0000269|PubMed:16038615, ECO:0000269|PubMed:18590734};
GN Name=PDEalpha {ECO:0000303|PubMed:18590734};
GN Synonyms=PDE1 {ECO:0000303|PubMed:16038615};
GN ORFNames=PF3D7_1209500.1 {ECO:0000312|EMBL:CZT99257.1},
GN PFL0475w {ECO:0000312|EMBL:ABS50256.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|EMBL:ABS50256.1};
RN [1] {ECO:0000312|EMBL:BAE54522.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=3D7 {ECO:0000312|EMBL:BAE54522.1};
RX PubMed=16038615; DOI=10.1042/bj20050425;
RA Yuasa K., Mi-Ichi F., Kobayashi T., Yamanouchi M., Kotera J., Kita K.,
RA Omori K.;
RT "PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria
RT parasite Plasmodium falciparum.";
RL Biochem. J. 392:221-229(2005).
RN [2] {ECO:0000312|EMBL:ABS50256.1, ECO:0000312|EMBL:ABS50257.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=3D7 {ECO:0000312|EMBL:ABS50256.1};
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 [3] {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).
CC -!- FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a
CC key regulator of many important physiological processes.
CC {ECO:0000269|PubMed:16038615, ECO:0000269|PubMed:18590734}.
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:0000269|PubMed:16038615, ECO:0000269|PubMed:18590734};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18590734};
CC Note=Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per
CC subunit: site 1 preferentially binds zinc, while site 2 has a
CC preference for magnesium (By similarity). Tightly binds zinc (By
CC similarity). {ECO:0000250|UniProtKB:O76083};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16038615};
CC Note=Binds 1 Mg(2+) ion per subunit. Binds 2 divalent metal cations per
CC subunit: site 1 preferentially binds zinc, while site 2 has a
CC preference for magnesium (By similarity). Binds magnesium less tightly
CC than zinc (By similarity). {ECO:0000250|UniProtKB:O76083};
CC -!- ACTIVITY REGULATION: Not inhibited by cAMP (PubMed:18590734). Inhibited
CC by zaprinast (PubMed:16038615, PubMed:18590734).
CC {ECO:0000269|PubMed:16038615, ECO:0000269|PubMed:18590734}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 uM for cGMP (for catalytic domain residues 610-954 and in
CC presence of Zn(2+)) {ECO:0000269|PubMed:18590734};
CC KM=0.65 uM for cGMP (for catalytic domain residues 610-954, in
CC presence of Mn(2+) and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:16038615};
CC Vmax=91 pmol/min/mg enzyme with cAMP as substrate (for catalytic
CC domain residues 610-954, in presence of Mn(2+) and at 37 degrees
CC Celsius) {ECO:0000269|PubMed:16038615};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC 3',5'-cyclic GMP: step 1/1. {ECO:0000269|PubMed:16038615,
CC ECO:0000269|PubMed:18590734}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:16038615,
CC ECO:0000305|PubMed:18590734}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PDEalphaA {ECO:0000303|PubMed:18590734};
CC IsoId=Q8I5V4-1; Sequence=Displayed;
CC Name=2; Synonyms=PDEalphaB {ECO:0000303|PubMed:18590734};
CC IsoId=Q8I5V4-2; Sequence=VSP_061031;
CC -!- DEVELOPMENTAL STAGE: Expressed at the ring stage during the asexual
CC blood stage. {ECO:0000269|PubMed:16038615,
CC ECO:0000269|PubMed:18590734}.
CC -!- DISRUPTION PHENOTYPE: Knockouts at the asexual blood stage are viable
CC and have normal merozoite formation in the host erythrocytes
CC (PubMed:18590734). cGMP hydrolysis is reduced by about 20% with no
CC effect on cAMP hydrolysis (PubMed:18590734).
CC {ECO:0000269|PubMed:18590734}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE54522.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB100091; BAE54522.1; ALT_INIT; mRNA.
DR EMBL; EF673784; ABS50256.1; -; mRNA.
DR EMBL; EF673785; ABS50257.1; -; mRNA.
DR EMBL; LN999947; CZT99257.1; -; Genomic_DNA.
DR EMBL; LN999947; CZT99258.1; -; Genomic_DNA.
DR RefSeq; XP_001350504.2; XM_001350468.2. [Q8I5V4-1]
DR AlphaFoldDB; Q8I5V4; -.
DR SMR; Q8I5V4; -.
DR STRING; 5833.PFL0475w; -.
DR EnsemblProtists; CZT99257; CZT99257; PF3D7_1209500.1. [Q8I5V4-1]
DR EnsemblProtists; CZT99258; CZT99258; PF3D7_1209500.2. [Q8I5V4-2]
DR GeneID; 811148; -.
DR KEGG; pfa:PF3D7_1209500.1; -.
DR VEuPathDB; PlasmoDB:PF3D7_1209500; -.
DR VEuPathDB; PlasmoDB:Pf7G8_120014500; -.
DR VEuPathDB; PlasmoDB:PfCD01_120014500; -.
DR VEuPathDB; PlasmoDB:PfDd2_120014300; -.
DR VEuPathDB; PlasmoDB:PfGA01_120014500; -.
DR VEuPathDB; PlasmoDB:PfGB4_120014500; -.
DR VEuPathDB; PlasmoDB:PfGN01_120015900; -.
DR VEuPathDB; PlasmoDB:PfHB3_120014700; -.
DR VEuPathDB; PlasmoDB:PfIT_120014900; -.
DR VEuPathDB; PlasmoDB:PfKE01_120014900; -.
DR VEuPathDB; PlasmoDB:PfKH01_120016000; -.
DR VEuPathDB; PlasmoDB:PfKH02_120014900; -.
DR VEuPathDB; PlasmoDB:PfML01_120015000; -.
DR VEuPathDB; PlasmoDB:PfSD01_120014600; -.
DR VEuPathDB; PlasmoDB:PfSN01_120015500; -.
DR VEuPathDB; PlasmoDB:PfTG01_120014900; -.
DR HOGENOM; CLU_302394_0_0_1; -.
DR InParanoid; Q8I5V4; -.
DR OMA; SRSFEAY; -.
DR OrthoDB; 161021at2759; -.
DR PhylomeDB; Q8I5V4; -.
DR BRENDA; 3.1.4.35; 4889.
DR UniPathway; UPA00763; UER00748.
DR Proteomes; UP000001450; Chromosome 12.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IDA: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 Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; cGMP; Hydrolase; Magnesium; Membrane; Metal-binding;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..954
FT /note="cGMP-specific 3',5'-cyclic phosphodiesterase alpha"
FT /id="PRO_0000452647"
FT TOPO_DOM 1..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..296
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..365
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 366..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 387..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423..432
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 433..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..954
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 586..930
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT ACT_SITE 680
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 680..684
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 684
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 720
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 721
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 721
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 721
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 832
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 832
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 884
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT VAR_SEQ 359..421
FT /note="SNTYQNNFVFQNMLFLLINIIYICIFCFLKNYMILYSFLYNCRFSIFCILFI
FT FLYYYLFFSLD -> N (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_061031"
SQ SEQUENCE 954 AA; 115412 MW; 111001581E069927 CRC64;
MMDTKVDQTI QPKFYVDKKL SKSFDNKLDE DIFNYPFKKE SFLKSEKFSF EHTKDSLWKC
IKEKAKKKSD MEYFNCVNNL CCKFICTIRK YVKYFLYLKD SSYEIYNINL YNNNNMNIIN
NKNITNNKNI TNNINNSFSN DYINYNHNYN HLNNSSSSKH NNYNVNNIDE KNIKNDYNTY
HNIYEQIFFK YNPSFYEYLM FTLMKKLIHY KNYIFNKTKK INNSYNNNDI KNIDGFLIFQ
NINFEEIFLN TFYSSFPFKL FLHSLYMIFI CFIYFVVLYF MLLKKIYTHP FIFHLSVLKF
LFDIIFFLSF ILYPLFLRLK RIDKIIYSSY ISSYIFVCVT FLYSFIIFKC SSYSVKMNSN
TYQNNFVFQN MLFLLINIIY ICIFCFLKNY MILYSFLYNC RFSIFCILFI FLYYYLFFSL
DFYRIIHLPL DNFFFPFLCF LFFSFLFIFK IIMSLYYEYV YEKKYRILFV KKNNLIEKRI
TKRKNTNINN AYFTKYFSID NTIPTSPIED ILNNFKHILE TINIIEENPN HNLTTNIMKI
KEKIKNCDNI LRTKNINQVQ IGKYRKFEKV YNIWCLDKMY LNYPLNQEET KSFLSNSLNR
ISFNSFSNMH SLLSSKFQEH YNDIYDWNGN IENIYKANTF ISIGYKLLYP LGVLEANFDK
EKLKKFLFRI CSYYNDIPYH TSLHAAQVAH FSKSMLFMLD MNHKISAIDE FCLHISSLCH
DTGHPGLNNY FLINSENNLA LTYNDNSVLE NYHCSLLFKT LKNPNYNIFE HYPYHIFISC
KKNIIKAILS TDMKNHFEYI SDFRTSKEFI DYDNLSNDQI WQIFCLILKA SDIGHSTLEW
NKHLEWTLKI NEEFYLQGLL EKSLNIQNSF LCDINTMNKL ALSQIDFLKH LCIPLFNELN
YICKNNDVYT HCIQPIENNI ERWESHKNDN QNLGLHEKYK EENLLSKLEL IKFE
