PDEB_PLAF7
ID PDEB_PLAF7 Reviewed; 1139 AA.
AC Q8I6Z7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase beta {ECO:0000305};
DE EC=3.1.4.35 {ECO:0000269|PubMed:30794532};
DE EC=3.1.4.53 {ECO:0000269|PubMed:30794532};
GN Name=PDEbeta {ECO:0000303|PubMed:18590734};
GN Synonyms=PDE2 {ECO:0000303|PubMed:18590734};
GN ORFNames=PF3D7_1321500.1 {ECO:0000312|EMBL:CAD52362.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|EMBL:ABS50258.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=3D7 {ECO:0000312|EMBL:ABS50258.1};
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:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=30794532; DOI=10.1371/journal.pbio.3000154;
RA Flueck C., Drought L.G., Jones A., Patel A., Perrin A.J., Walker E.M.,
RA Nofal S.D., Snijders A.P., Blackman M.J., Baker D.A.;
RT "Phosphodiesterase beta is the master regulator of cAMP signalling during
RT malaria parasite invasion.";
RL PLoS Biol. 17:e3000154-e3000154(2019).
CC -!- FUNCTION: Plays a role in signal transduction by regulating the
CC intracellular concentration of cyclic nucleotides cAMP and cGMP
CC (PubMed:30794532). Catalyzes the hydrolysis of both cAMP and cGMP to
CC 5'-AMP and 5'-GMP, respectively (PubMed:30794532). By regulating cAMP
CC levels during the asexual blood stage and, thus PKA activation,
CC required for merozoite invasion of erythrocytes and for the parasite
CC development immediately following invasion (PubMed:30794532).
CC {ECO:0000269|PubMed:30794532}.
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:30794532};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; EC=3.1.4.53;
CC Evidence={ECO:0000269|PubMed:30794532};
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:30794532}.
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000269|PubMed:30794532}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30794532,
CC ECO:0000305|PubMed:18590734}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30794532}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In early schizonts, localizes to the endoplasmic
CC reticulum (PubMed:30794532). Transported to an apical location and then
CC subsequently discharged to the plasma membrane of merozoites within
CC mature schizont (PubMed:30794532). {ECO:0000269|PubMed:30794532}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage, with
CC highest levels in the late schizont stage.
CC {ECO:0000269|PubMed:18590734, ECO:0000269|PubMed:30794532}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000255|RuleBase:RU363067}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF673786; ABS50258.1; -; mRNA.
DR EMBL; AL844509; CAD52362.1; -; Genomic_DNA.
DR RefSeq; XP_001349954.1; XM_001349918.1.
DR AlphaFoldDB; Q8I6Z7; -.
DR SMR; Q8I6Z7; -.
DR STRING; 5833.MAL13P1.118; -.
DR PRIDE; Q8I6Z7; -.
DR EnsemblProtists; CAD52362; CAD52362; PF3D7_1321500.1.
DR GeneID; 813666; -.
DR KEGG; pfa:PF3D7_1321500.1; -.
DR VEuPathDB; PlasmoDB:PF3D7_1321500; -.
DR HOGENOM; CLU_278061_0_0_1; -.
DR InParanoid; Q8I6Z7; -.
DR OMA; SRTKYNW; -.
DR OrthoDB; 161021at2759; -.
DR PhylomeDB; Q8I6Z7; -.
DR Reactome; R-PFA-111957; Cam-PDE 1 activation.
DR Reactome; R-PFA-165160; PDE3B signalling.
DR Reactome; R-PFA-418457; cGMP effects.
DR Reactome; R-PFA-418555; G alpha (s) signalling events.
DR UniPathway; UPA00762; UER00747.
DR UniPathway; UPA00763; UER00748.
DR Proteomes; UP000001450; Chromosome 13.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
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:0004117; F:calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity; ISS:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046069; P:cGMP catabolic process; IDA:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISS:GeneDB.
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 cAMP; Cell membrane; cGMP; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1139
FT /note="Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase
FT beta"
FT /id="PRO_0000452648"
FT TOPO_DOM 1..429
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 430..450
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 451..462
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 463..483
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 484..498
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 499..519
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 520..536
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 558..564
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 565..585
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 586..592
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..1139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 775..1098
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 847
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 847..851
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 851
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 887
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 888
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 888
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 888
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 1000
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 1000
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT BINDING 1052
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /evidence="ECO:0000255|PIRSR:PIRSR623088-2"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1139 AA; 133168 MW; 84A467712F0E67ED CRC64;
MGKVEDFEEH NKNSNQDIEK NVGNRRRSNS NTINDQNENI NKNKAIVTKK SFIMNLLRNK
EKTKVEQNDD NIVENMNERK NSLKDMSLIS DNVEKDNKVK KKNSYLKNLN ILGKTKSIEF
SFPSNILNNA RKNIQEIDEE SPLTSNSLRT YKEGISEDNR QNQRNADNNS LNWSTSNINT
ECNSEFSNIE VKVLKTEKSN SVKLKDNIID IPNDKNKKEL QEINIKNTNK DSYKNLYLKV
RNSISFNDNI KIDDENKNDK NNIIDNYNNY DDINSSNEIT IDGLNHDDNI KKIDNINNFD
NKHDDNLQDH HQNHVHHTFR SSRKSLGNIK SNNTNIKLNN DKNFDTNINK RSILEKYFYD
IWKRNITIKK EIYSLSSKNP PNPLKSTFAD ACQNESSEKE LLKKIPLKFN DDSIESLYVL
NLNNWISSRM IIIGIVMLIL SFIIWPLTTW SLKTSTWGRE TYIIILFHTL MAINTLILIF
FIIIGSTELC KYSECMSYVL FSLMVALWGL WNIAIGLTLE YNPNLSEMPT TTYELEMIYV
LTYIYGFLPL VIIDIFFPSR TKYNWIIHLI FIFLNSSSII LVGSAKPDFV PEIYVVFRIL
AYTTLCIFLY IGSYTSELQI RYVFYNLLVA GYKLDKIESD MKNKTSNKKI STGIEDLINM
LKECTKVILE LENETDTNFN VHTKTSYCSN ILEQCLSTLT KSDNLYNIDY NVLENPENKK
FIEAYVSKSK SNFAGEEVPK GVDFKLNKSF SNNDCISTDK VDLDKKQIKK FLKQINISQL
TKMIQFIDNK LLSDWDFNCL TYFDESEYPF FDINLSLICT IDHNIPINII INFLCFVEKQ
YNNVPYHNTI HATMVTQKFF CLAKKLGIYD DLEYKIKLVM FISGICHDIG HPGYNNLFFV
NSLHPLSIIY NDISVLENYH ASITFKILQL NQCNILKNFS EKDFRMMRSY IIELILSTDM
KHHFEIISKF RIRRENEDFD YIKNSDDLLI LTKMIIKSAD ISHGSVSWSE HYCWCQRVLS
EFYTQGDEEL KNKMPLSPLC DRTKHNEVCK SQITFLKFVV MPLFEELSHI DNNKFIKSFC
LKRLNSNCIM WDTLMKEEKT IEVYDPAAVK LKDKKKKKVD KKKKSYIDLT LFFIKNVSD
