PDE1C_RAT
ID PDE1C_RAT Reviewed; 768 AA.
AC Q63421;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C {ECO:0000305|PubMed:7568196};
DE Short=Cam-PDE 1C;
DE EC=3.1.4.17 {ECO:0000269|PubMed:7568196};
GN Name=Pde1c {ECO:0000312|RGD:68332};
GN Synonyms=Pde1c2 {ECO:0000303|PubMed:7568196};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Olfactory epithelium;
RX PubMed=7568196; DOI=10.1073/pnas.92.21.9677;
RA Yan C., Zhao A.Z., Bentley J.K., Loughney K., Ferguson K., Beavo J.A.;
RT "Molecular cloning and characterization of a calmodulin-dependent
RT phosphodiesterase enriched in olfactory sensory neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:9677-9681(1995).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Calmodulin-dependent cyclic nucleotide phosphodiesterase with
CC a dual specificity for the second messengers cAMP and cGMP, which are
CC key regulators of many important physiological processes. Has a high
CC affinity for both cAMP and cGMP (PubMed:7568196). Modulates the
CC amplitude and duration of the cAMP signal in sensory cilia in response
CC to odorant stimulation, hence contributing to the generation of action
CC potentials. Regulates smooth muscle cell proliferation. Regulates the
CC stability of growth factor receptors, including PDGFRB (By similarity).
CC {ECO:0000250|UniProtKB:Q14123, ECO:0000269|PubMed:7568196}.
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:7568196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:7568196};
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:7568196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:7568196};
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:7568196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:7568196};
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+). {ECO:0000269|PubMed:7568196}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 uM for 3',5'-cyclic AMP (at pH 7.5)
CC {ECO:0000269|PubMed:7568196};
CC KM=1.1 uM for 3',5'-cyclic GMP (at pH 7.5)
CC {ECO:0000269|PubMed:7568196};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P14100}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q64338}.
CC -!- TISSUE SPECIFICITY: Highly expressed in olfactory epithelium and at
CC moderate levels, in cerebellum, as well as weakly in forebrain, testis,
CC heart and lung (PubMed:7568196). In the olfactory epithelium, expressed
CC by sensory neurons, but not epithelial cells (PubMed:7568196).
CC {ECO:0000269|PubMed:7568196}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE1 subfamily. {ECO:0000305}.
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DR EMBL; L41045; AAB00868.1; -; mRNA.
DR PIR; T10796; T10796.
DR RefSeq; NP_112340.1; NM_031078.2.
DR AlphaFoldDB; Q63421; -.
DR SMR; Q63421; -.
DR STRING; 10116.ENSRNOP00000017531; -.
DR BindingDB; Q63421; -.
DR ChEMBL; CHEMBL2111322; -.
DR DrugCentral; Q63421; -.
DR iPTMnet; Q63421; -.
DR PhosphoSitePlus; Q63421; -.
DR PaxDb; Q63421; -.
DR PRIDE; Q63421; -.
DR GeneID; 81742; -.
DR KEGG; rno:81742; -.
DR UCSC; RGD:68332; rat.
DR CTD; 5137; -.
DR RGD; 68332; Pde1c.
DR eggNOG; KOG3688; Eukaryota.
DR InParanoid; Q63421; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q63421; -.
DR Reactome; R-RNO-111957; Cam-PDE 1 activation.
DR PRO; PR:Q63421; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005929; C:cilium; ISO:RGD.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISO:RGD.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; ISO:RGD.
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:0030552; F:cAMP binding; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0051592; P:response to calcium ion; IDA:MGI.
DR GO; GO:0007608; P:sensory perception of smell; IEP:RGD.
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 Acetylation; Calmodulin-binding; cAMP; cGMP; Hydrolase; Lysosome;
KW Magnesium; Metal-binding; Olfaction; Reference proteome;
KW Sensory transduction; Zinc.
FT CHAIN 1..768
FT /note="Dual specificity calcium/calmodulin-dependent 3',5'-
FT cyclic nucleotide phosphodiesterase 1C"
FT /id="PRO_0000198794"
FT DOMAIN 211..588
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 183..206
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P14100"
FT REGION 513..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 584..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..555
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..613
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 631..645
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 646..694
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..711
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 288
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 329
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT BINDING 436
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q01064"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q14123"
SQ SEQUENCE 768 AA; 86671 MW; 8816C208A30DD55E CRC64;
MTDTSHKKEG FKKCRSATFS IDGYSFTIVA NEAGDKNARP LARFSRSKSQ NCLWNSLIDG
LTGNVKEKPR PTIVQDTRPP EEILADELPQ LDSPEALVKT SFRLRSLVKQ LERGEASVVD
LKKNLEYAAT VLESVYIDET RRLLDTEDEL SDIQSDAVPS EVRDWLASTF TRQMGMMLRR
SDEKPRFKSI VHAVQAGIFV ERMYRRTSNM VGLSYPPAVI DALKDVDTWS FDVFSLNEAS
GDHALKFIFY ELLTRYDLIS RFKIPISALV SFVEALEVGY SKHKNPYHNL MHAADVTQTV
HYLLYKTGVA NWLTELEIFA IIFSAAIHDY EHTGTTNNFH IQTRSDPAIL YNDRSVLENH
HLSAAYRLLQ EDEEMNILVN LSKDDWREFR TLVIEMVMAT DMSCHFQQIK AMKTALQQPE
AIEKPKALSL MLHTADISHP AKAWDLHHRW TMSLLEEFFR QGDREAELGL PFSPLCDRKS
TMVAQSQVGF IDFIVEPTFT VLTDMTEKIV SPLIDETSQT GGTGQRRSSL NSINSSDAKR
SGVKSSGSEG SAPINNSVIP VDYKSFKATW TEVVQINRER WRAKVPKEEK AKKEAEEKAR
LAAEEKQKEM EAKSQAEQGT TSKAEKKTSG ETKGQVNGTR TSKGDNPRGK NSKGDKAGEK
QQNGDLKDGK NKADKKDHSN TGNESKKADG TKKRSHGSPA PSTSSTSRLT LPVIKPPLRH
FKRPAYASSS YAPSVPKKTD DHPVRYKMLD QRIKIKKIQN ISHHWNKK
