PDE1_DROME
ID PDE1_DROME Reviewed; 834 AA.
AC B7YZV4; Q9VKE9;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 {ECO:0000305|PubMed:15673286};
DE Short=PDE1 {ECO:0000303|PubMed:15673286};
DE EC=3.1.4.17 {ECO:0000269|PubMed:15673286};
GN Name=Pde1c {ECO:0000312|FlyBase:FBgn0264815};
GN ORFNames=CG44007 {ECO:0000312|FlyBase:FBgn0264815};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM48425.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM48425.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM48425.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=15673286; DOI=10.1042/bj20050057;
RA Day J.P., Dow J.A.T., Houslay M.D., Davies S.A.;
RT "Cyclic nucleotide phosphodiesterases in Drosophila melanogaster.";
RL Biochem. J. 388:333-342(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20551439; DOI=10.1534/genetics.110.118018;
RA Morton D.B., Clemens-Grisham R., Hazelett D.J., Vermehren-Schmaedick A.;
RT "Infertility and male mating behavior deficits associated with Pde1c in
RT Drosophila melanogaster.";
RL Genetics 186:159-165(2010).
CC -!- FUNCTION: Cyclic nucleotide phosphodiesterase with a dual specificity
CC for the second messengers cAMP and cGMP, which are key regulators of
CC many important physiological processes (PubMed:15673286). Required for
CC male fertility and male mating behavior (PubMed:20551439).
CC {ECO:0000269|PubMed:15673286, ECO:0000269|PubMed:20551439}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-
CC phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
CC Evidence={ECO:0000269|PubMed:15673286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:15673286};
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; Evidence={ECO:0000269|PubMed:15673286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:15673286};
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; Evidence={ECO:0000269|PubMed:15673286};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:15673286};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q01064};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000250|UniProtKB:Q01064};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q01064};
CC Note=Binds 2 divalent metal cations per subunit. Site 2 has a
CC preference for magnesium ions. {ECO:0000250|UniProtKB:Q01064};
CC -!- ACTIVITY REGULATION: Type I PDE are activated by the binding of
CC calmodulin in the presence of Ca(2+) (PubMed:15673286). Inhibited by
CC zaprinast and sildenafil (PubMed:15673286).
CC {ECO:0000269|PubMed:15673286}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.3 uM for 3',5'-cyclic GMP {ECO:0000269|PubMed:15673286};
CC KM=20.5 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:15673286};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000312|FlyBase:FBgn0264815}; Synonyms=G
CC {ECO:0000312|FlyBase:FBgn0264815};
CC IsoId=B7YZV4-1; Sequence=Displayed;
CC Name=C {ECO:0000312|FlyBase:FBgn0264815};
CC IsoId=B7YZV4-2; Sequence=VSP_058752;
CC -!- TISSUE SPECIFICITY: Expressed in the head (at protein level)
CC (PubMed:15673286). Expressed in Malpighian tubules (PubMed:15673286).
CC Expressed in neurons in the brain and ventral ganglia with male flies
CC having higher levels of expression in the abdominal ganglia compared to
CC female flies (PubMed:20551439). {ECO:0000269|PubMed:15673286,
CC ECO:0000269|PubMed:20551439}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE1 subfamily. {ECO:0000305}.
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DR EMBL; AE014134; AAF53123.1; -; Genomic_DNA.
DR EMBL; AE014134; ACL83022.1; -; Genomic_DNA.
DR EMBL; AE014134; ACL83026.1; -; Genomic_DNA.
DR EMBL; AY118396; AAM48425.1; -; mRNA.
DR RefSeq; NP_001137816.1; NM_001144344.2. [B7YZV4-1]
DR RefSeq; NP_001137820.1; NM_001144348.4. [B7YZV4-1]
DR RefSeq; NP_609520.1; NM_135676.6. [B7YZV4-2]
DR AlphaFoldDB; B7YZV4; -.
DR SMR; B7YZV4; -.
DR STRING; 7227.FBpp0289061; -.
DR DNASU; 34594; -.
DR EnsemblMetazoa; FBtr0334136; FBpp0306253; FBgn0264815. [B7YZV4-1]
DR EnsemblMetazoa; FBtr0334137; FBpp0306254; FBgn0264815. [B7YZV4-2]
DR EnsemblMetazoa; FBtr0334140; FBpp0306257; FBgn0264815. [B7YZV4-1]
DR GeneID; 34594; -.
DR KEGG; dme:Dmel_CG44007; -.
DR CTD; 5137; -.
DR FlyBase; FBgn0264815; Pde1c.
DR VEuPathDB; VectorBase:FBgn0264815; -.
DR eggNOG; KOG3688; Eukaryota.
DR HOGENOM; CLU_005940_0_1_1; -.
DR OMA; HHRWTMQ; -.
DR Reactome; R-DME-111957; Cam-PDE 1 activation.
DR Reactome; R-DME-418457; cGMP effects.
DR Reactome; R-DME-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 34594; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Pde1c; fly.
DR GenomeRNAi; 34594; -.
DR PRO; PR:B7YZV4; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0264815; Expressed in brain and 21 other tissues.
DR ExpressionAtlas; B7YZV4; baseline and differential.
DR GO; GO:0005615; C:extracellular space; HDA:FlyBase.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:FlyBase.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:FlyBase.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; ISM:FlyBase.
DR GO; GO:0048101; F:calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046058; P:cAMP metabolic process; IDA:FlyBase.
DR GO; GO:0046068; P:cGMP metabolic process; IDA:FlyBase.
DR GO; GO:0060179; P:male mating behavior; IMP:FlyBase.
DR GO; GO:0019953; P:sexual reproduction; HEP:FlyBase.
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 InterPro; IPR013706; PDEase_N.
DR Pfam; PF00233; PDEase_I; 1.
DR Pfam; PF08499; PDEase_I_N; 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 Alternative splicing; Behavior; cAMP; cGMP; Hydrolase; Magnesium;
KW Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..834
FT /note="Dual specificity calcium/calmodulin-dependent 3',5'-
FT cyclic nucleotide phosphodiesterase 1"
FT /id="PRO_0000438861"
FT DOMAIN 392..786
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 152..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 364..387
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P14100"
FT REGION 720..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 797..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 469
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 473
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 509
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 510
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 510
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 617
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT VAR_SEQ 1..322
FT /note="MQPSSPNATNYLADNIQISSANLSQTEMVVGRDSADYTAMHSINVGVGNSFL
FT RGDTDIPQESGHSFETPSNMSFTAGQWDTESLPPVDTPDALNKAAGRIRSLLRRMDHET
FT VAYEDMQRNLHYAARVLEAVFIDESREGCNGNCKNLNCSRHSHGRDDQQQDNNNSNRSC
FT SLQEASPGGAGAGVTPGADNQDSIESRTKGVSQAPQTHSGPTGPPSNTSSETIAQPAPK
FT LQPALETVRESVMEESPSKDPGDKGPPPPASTSTLTSQTTTSSSATAEPSAKAAESQAG
FT SAGSSGSCSNPAAVHRQRRLRTPTWARSMSTNKT -> MYEPGTSSEEGVVSETEPEPA
FT GVSVSVSVSVSEEPSASRSSRLTVITVVVVVVAVRAMSRLRRESSRQSVITVELIQFII
FT QYRAKETQEKKKR (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_058752"
SQ SEQUENCE 834 AA; 91455 MW; D027A9481010C665 CRC64;
MQPSSPNATN YLADNIQISS ANLSQTEMVV GRDSADYTAM HSINVGVGNS FLRGDTDIPQ
ESGHSFETPS NMSFTAGQWD TESLPPVDTP DALNKAAGRI RSLLRRMDHE TVAYEDMQRN
LHYAARVLEA VFIDESREGC NGNCKNLNCS RHSHGRDDQQ QDNNNSNRSC SLQEASPGGA
GAGVTPGADN QDSIESRTKG VSQAPQTHSG PTGPPSNTSS ETIAQPAPKL QPALETVRES
VMEESPSKDP GDKGPPPPAS TSTLTSQTTT SSSATAEPSA KAAESQAGSA GSSGSCSNPA
AVHRQRRLRT PTWARSMSTN KTRLADEDDE LSEVQPDAVP PEVREWLAST FTRQMATSRR
KSDEKPKFRS VAHAIRAGIF VDRMYRRVSS SALTAFPPDV VRLLKNLDDW TFDVFALTEA
ASGQVVKYVA YELFNRYGSI HKFKIAPGIL EAFLHRVEEG YCRYRNPYHN NLHAVDVMQT
IHYCLCNTGL MNWLTDLEIF ASLLAALLHD YEHTGTTNNF HVMSGSETAL LYNDRAVLEN
HHASASFRLL REDEYNILSH LSREEFRELR GLVIEMVLGT DMTNHFQQMK AMRQLLTLQE
ATIDKQKVLS LVLHCCDISH PAKQWGVHHR WTMLLLEEFF RQGDLEKELG LPFSPLCDRN
NTLVAESQIC FIDFIVEPSM GVMSDMLELI LAPIAPMNKS KPATLVEHET TANSTTNSAI
VIPNSGITPS MDKPRDHRTE AKTTAAECLA RKSVTGTTAS KFNIPKPWLT CLVENKRIWK
EQAVKDAEAR ALATAAEEAA AAAAAEAEES KPETETADGE QSEPAAEPAD GAAA
