PDE1A_BOVIN
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 03-AUG-2022, entry version 164.
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. [P14100-1]
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; P14100; -.
DR Ensembl; ENSBTAT00000016060; ENSBTAP00000016060; ENSBTAG00000012100. [P14100-2]
DR Ensembl; ENSBTAT00000052318; ENSBTAP00000051204; ENSBTAG00000012100. [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; LFRRSNM; -.
DR OrthoDB; 904682at2759; -.
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 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:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
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; -; 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; 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
