ID   PDE1A_BOVIN             Reviewed;         530 AA.
AC   P14100; Q08E30; Q28063;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 173.
DE   RecName: Full=Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A {ECO:0000305|PubMed:8537356};
DE            Short=Cam-PDE 1A;
DE            EC=3.1.4.17 {ECO:0000269|PubMed:8537356};
DE   AltName: Full=61 kDa Cam-PDE {ECO:0000303|PubMed:1651111};
GN   Name=PDE1A {ECO:0000250|UniProtKB:P54750};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=7678006; DOI=10.1016/s0021-9258(18)54200-9;
RA   Sonnenburg W.K., Seger D., Beavo J.A.;
RT   "Molecular cloning of a cDNA encoding the '61-kDa' calmodulin-stimulated
RT   cyclic nucleotide phosphodiesterase. Tissue-specific expression of
RT   structurally related isoforms.";
RL   J. Biol. Chem. 268:645-652(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP   ACTIVITY REGULATION, SUBUNIT, AND REGION.
RC   TISSUE=Lung;
RX   PubMed=8537356; DOI=10.1074/jbc.270.52.30989;
RA   Sonnenburg W.K., Seger D., Kwak K.S., Huang J., Charbonneau H., Beavo J.A.;
RT   "Identification of inhibitory and calmodulin-binding domains of the PDE1A1
RT   and PDE1A2 calmodulin-stimulated cyclic nucleotide phosphodiesterases.";
RL   J. Biol. Chem. 270:30989-31000(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=Hereford; TISSUE=Hippocampus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PROTEIN SEQUENCE OF 2-530 (ISOFORM 2), AND REGION.
RC   TISSUE=Brain;
RX   PubMed=1651111; DOI=10.1021/bi00246a009;
RA   Charbonneau H., Kumar S., Novack J.P., Blumenthal D.K., Griffin P.R.,
RA   Shabanowitz J., Hunt D.F., Beavo J.A., Walsh K.A.;
RT   "Evidence for domain organization within the 61-kDa calmodulin-dependent
RT   cyclic nucleotide phosphodiesterase from bovine brain.";
RL   Biochemistry 30:7931-7940(1991).
RN   [5]
RP   PROTEIN SEQUENCE OF 194-427.
RC   TISSUE=Brain;
RX   PubMed=3025833; DOI=10.1073/pnas.83.24.9308;
RA   Charbonneau H., Beier N., Walsh K.A., Beavo J.A.;
RT   "Identification of a conserved domain among cyclic nucleotide
RT   phosphodiesterases from diverse species.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:9308-9312(1986).
RN   [6]
RP   PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Brain;
RX   PubMed=1651112; DOI=10.1021/bi00246a010;
RA   Novack J.P., Charbonneau H., Bentley J.K., Walsh K.A., Beavo J.A.;
RT   "Sequence comparison of the 63-, 61-, and 59-kDa calmodulin-dependent
RT   cyclic nucleotide phosphodiesterases.";
RL   Biochemistry 30:7940-7947(1991).
CC   -!- FUNCTION: Calcium/calmodulin-dependent cyclic nucleotide
CC       phosphodiesterase with a dual specificity for the second messengers
CC       cGMP and cAMP, which are key regulators of many important physiological
CC       processes. Has a higher efficiency with cGMP compared to cAMP.
CC       {ECO:0000269|PubMed:8537356}.
CC   -!- CATALYTIC ACTIVITY: [Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A]:
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:8537356};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC         Evidence={ECO:0000305|PubMed:8537356};
CC   -!- CATALYTIC ACTIVITY: [Isoform 1]:
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:8537356};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC         Evidence={ECO:0000305|PubMed:8537356};
CC   -!- CATALYTIC ACTIVITY: [Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A]:
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:8537356};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC         Evidence={ECO:0000305|PubMed:8537356};
CC   -!- CATALYTIC ACTIVITY: [Isoform 1]:
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:8537356};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC         Evidence={ECO:0000305|PubMed:8537356};
CC   -!- CATALYTIC ACTIVITY: [Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A]:
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:0000250|UniProtKB:P54750};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000250|UniProtKB:P54750};
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: [Dual specificity calcium/calmodulin-dependent
CC       3',5'-cyclic nucleotide phosphodiesterase 1A]: Type I PDE are activated
CC       by the binding of calmodulin in the presence of Ca(2+).
CC       {ECO:0000250|UniProtKB:Q61481}.
CC   -!- ACTIVITY REGULATION: [Isoform 1]: Type I PDE are activated by the
CC       binding of calmodulin in the presence of Ca(2+).
CC       {ECO:0000250|UniProtKB:Q61481}.
CC   -!- SUBUNIT: Homodimer (PubMed:8537356). Interacts with YWHAZ (By
CC       similarity). {ECO:0000250|UniProtKB:P54750,
CC       ECO:0000269|PubMed:8537356}.
CC   -!- INTERACTION:
CC       P14100; P61602: NCALD; NbExp=2; IntAct=EBI-907809, EBI-908133;
CC       P14100; P84076: Hpca; Xeno; NbExp=2; IntAct=EBI-907809, EBI-908193;
CC       P14100; P62168: Ncs1; Xeno; NbExp=2; IntAct=EBI-907809, EBI-907774;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=2; Synonyms=PDE1A2 {ECO:0000303|PubMed:8537356}, 61 kDa Cam-PDE
CC       {ECO:0000303|PubMed:1651111};
CC         IsoId=P14100-1; Sequence=Displayed;
CC       Name=1; Synonyms=PDE1A1 {ECO:0000303|PubMed:8537356}, 59-kDa CaM-PDE
CC       {ECO:0000303|PubMed:1651112};
CC         IsoId=P14100-2; Sequence=VSP_004546;
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       PDE1 subfamily. {ECO:0000305}.
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DR   EMBL; M90358; AAA74560.1; -; mRNA.
DR   EMBL; L34069; AAA92555.1; -; mRNA.
DR   EMBL; BC123449; AAI23450.1; -; mRNA.
DR   PIR; A45334; A45334.
DR   RefSeq; NP_776839.1; NM_174414.3. [P14100-2]
DR   RefSeq; XP_010800147.1; XM_010801845.1.
DR   AlphaFoldDB; P14100; -.
DR   SMR; P14100; -.
DR   BioGRID; 159260; 2.
DR   IntAct; P14100; 3.
DR   STRING; 9913.ENSBTAP00000051204; -.
DR   BindingDB; P14100; -.
DR   ChEMBL; CHEMBL3774; -.
DR   DrugCentral; P14100; -.
DR   iPTMnet; P14100; -.
DR   PaxDb; 9913-ENSBTAP00000051204; -.
DR   Ensembl; ENSBTAT00000016060.6; ENSBTAP00000016060.5; ENSBTAG00000012100.6. [P14100-2]
DR   Ensembl; ENSBTAT00000052318.2; ENSBTAP00000051204.1; ENSBTAG00000012100.6. [P14100-1]
DR   GeneID; 281969; -.
DR   KEGG; bta:281969; -.
DR   CTD; 5136; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012100; -.
DR   eggNOG; KOG3688; Eukaryota.
DR   GeneTree; ENSGT00940000157043; -.
DR   HOGENOM; CLU_005940_1_3_1; -.
DR   InParanoid; P14100; -.
DR   OMA; MSHPPAE; -.
DR   TreeFam; TF314638; -.
DR   Reactome; R-BTA-111957; Cam-PDE 1 activation.
DR   Reactome; R-BTA-418457; cGMP effects.
DR   Reactome; R-BTA-418555; G alpha (s) signalling events.
DR   SABIO-RK; P14100; -.
DR   Proteomes; UP000009136; Chromosome 2.
DR   Bgee; ENSBTAG00000012100; Expressed in occipital lobe and 96 other cell types or tissues.
DR   GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0048101; F:calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity; IDA:MGI.
DR   GO; GO:0004117; F:calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity; IDA:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 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   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   PANTHER; PTHR11347:SF34; DUAL SPECIFICITY CALCIUM_CALMODULIN-DEPENDENT 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 1A; 1.
DR   Pfam; PF00233; PDEase_I; 1.
DR   Pfam; PF08499; PDEase_I_N; 1.
DR   PRINTS; PR00387; PDIESTERASE1.
DR   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calmodulin-binding; cAMP; cGMP;
KW   Direct protein sequencing; Hydrolase; Magnesium; Metal-binding;
KW   Reference proteome; Zinc.
FT   CHAIN           1..530
FT                   /note="Dual specificity calcium/calmodulin-dependent 3',5'-
FT                   cyclic nucleotide phosphodiesterase 1A"
FT                   /id="PRO_0000198784"
FT   DOMAIN          142..508
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          24..44
FT                   /note="Calmodulin-binding"
FT                   /evidence="ECO:0000269|PubMed:1651111"
FT   REGION          114..137
FT                   /note="Calmodulin-binding"
FT                   /evidence="ECO:0000269|PubMed:8537356"
FT   REGION          450..471
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          502..530
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        454..471
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        219
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O76083"
FT   BINDING         223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q01064"
FT   BINDING         259
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q01064"
FT   BINDING         260
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q01064"
FT   BINDING         260
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q01064"
FT   BINDING         366
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q01064"
FT   VAR_SEQ         1..34
FT                   /note="MGSTATETEELENTTFKYLIGEQTEKMWQRLKGI -> MDDHVTIRRKHLQR
FT                   PIFR (in isoform 1)"
FT                   /evidence="ECO:0000303|PubMed:8537356, ECO:0000303|Ref.3"
FT                   /id="VSP_004546"
FT   CONFLICT        237
FT                   /note="H -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        321
FT                   /note="N -> W (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   530 AA;  60843 MW;  24CF83E5211AE06F CRC64;
     MGSTATETEE LENTTFKYLI GEQTEKMWQR LKGILRCLVK QLEKGDVNVI DLKKNIEYAA
     SVLEAVYIDE TRRLLDTDDE LSDIQSDSVP SEVRDWLAST FTRKMGMMKK KSEEKPRFRS
     IVHVVQAGIF VERMYRKSYH MVGLAYPEAV IVTLKDVDKW SFDVFALNEA SGEHSLKFMI
     YELFTRYDLI NRFKIPVSCL IAFAEALEVG YSKYKNPYHN LIHAADVTQT VHYIMLHTGI
     MHWLTELEIL AMVFAAAIHD YEHTGTTNNF HIQTRSDVAI LYNDRSVLEN HHVSAAYRLM
     QEEEMNVLIN LSKDDWRDLR NLVIEMVLST DMSGHFQQIK NIRNSLQQPE GLDKAKTMSL
     ILHAADISHP AKSWKLHHRW TMALMEEFFL QGDKEAELGL PFSPLCDRKS TMVAQSQIGF
     IDFIVEPTFS LLTDSTEKII IPLIEEDSKT KTPSYGASRR SNMKGTTNDG TYSPDYSLAS
     VDLKSFKNSL VDIIQQNKER WKELAAQGEP DPHKNSDLVN AEEKHAETHS
//