PDE1A_HUMAN
ID PDE1A_HUMAN Reviewed; 535 AA.
AC P54750; D3DPG5; Q86VZ0; Q9C0K8; Q9C0K9; Q9C0L0; Q9C0L1; Q9C0L2; Q9C0L3;
AC Q9C0L4; Q9UFX3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A {ECO:0000305|PubMed:8557689};
DE Short=Cam-PDE 1A;
DE EC=3.1.4.17 {ECO:0000269|PubMed:8557689};
DE AltName: Full=61 kDa Cam-PDE {ECO:0000303|PubMed:8557689};
DE AltName: Full=hCam-1 {ECO:0000303|PubMed:8557689};
GN Name=PDE1A {ECO:0000312|HGNC:HGNC:8774};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8557689; DOI=10.1074/jbc.271.2.796;
RA Loughney K., Martins T.J., Harris E.A.S., Sadhu K., Hicks J.B.,
RA Sonnenburg W.K., Beavo J.A., Ferguson K.;
RT "Isolation and characterization of cDNAs corresponding to two human
RT calcium, calmodulin-regulated, 3',5'-cyclic nucleotide
RT phosphodiesterases.";
RL J. Biol. Chem. 271:796-806(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 9).
RC TISSUE=Heart;
RX PubMed=11342109; DOI=10.1016/s0167-4781(00)00293-1;
RA Michibata H., Yanaka N., Kanoh Y., Okumura K., Omori K.;
RT "Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice
RT variants, their specific expression, genomic organization, and chromosomal
RT localization.";
RL Biochim. Biophys. Acta 1517:278-287(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11747989; DOI=10.1016/s0898-6568(01)00207-8;
RA Fidock M.D., Miller M., Lanfear J.;
RT "Isolation and differential tissue distribution of two human cDNAs encoding
RT PDE1 splice variants.";
RL Cell. Signal. 14:53-60(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH YWHAZ.
RX PubMed=16959763; DOI=10.1074/mcp.m600147-mcp200;
RA Angrand P.O., Segura I., Voelkel P., Ghidelli S., Terry R., Brajenovic M.,
RA Vintersten K., Klein R., Superti-Furga G., Drewes G., Kuster B.,
RA Bouwmeester T., Acker-Palmer A.;
RT "Transgenic mouse proteomics identifies new 14-3-3-associated proteins
RT involved in cytoskeletal rearrangements and cell signaling.";
RL Mol. Cell. Proteomics 5:2211-2227(2006).
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:8557689}.
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:8557689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:8557689};
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:8557689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:8557689};
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:8557689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:8557689};
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:0000250|UniProtKB:Q61481}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with YWHAZ
CC (PubMed:16959763). {ECO:0000250|UniProtKB:P14100,
CC ECO:0000269|PubMed:16959763}.
CC -!- INTERACTION:
CC P54750-4; P42858: HTT; NbExp=3; IntAct=EBI-25952361, EBI-466029;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1; Synonyms=PDE1A3, PDE1A6;
CC IsoId=P54750-1; Sequence=Displayed;
CC Name=2; Synonyms=PDE1A4, PDE1A5;
CC IsoId=P54750-2; Sequence=VSP_004547;
CC Name=3; Synonyms=PDE1A10;
CC IsoId=P54750-3; Sequence=VSP_004548;
CC Name=4; Synonyms=PDE1A5;
CC IsoId=P54750-4; Sequence=VSP_004549;
CC Name=5; Synonyms=PDE1A9;
CC IsoId=P54750-5; Sequence=VSP_004550;
CC Name=6; Synonyms=PDE1A1;
CC IsoId=P54750-6; Sequence=VSP_004547, VSP_004549;
CC Name=7; Synonyms=PDE1A8;
CC IsoId=P54750-7; Sequence=VSP_004547, VSP_004550;
CC Name=8; Synonyms=PDE1A11;
CC IsoId=P54750-8; Sequence=VSP_004548, VSP_004549;
CC Name=9; Synonyms=PDE1A12;
CC IsoId=P54750-9; Sequence=VSP_004548, VSP_004550;
CC -!- TISSUE SPECIFICITY: Several tissues, including brain, kidney, testes
CC and heart.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE1 subfamily. {ECO:0000305}.
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DR EMBL; U40370; AAC50436.1; -; mRNA.
DR EMBL; AB038224; BAB20049.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20050.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20051.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20052.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20053.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20054.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20055.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20056.1; -; Genomic_DNA.
DR EMBL; AB038224; BAB20057.1; -; Genomic_DNA.
DR EMBL; AJ401610; CAC82208.1; -; mRNA.
DR EMBL; AL110263; CAB53703.1; -; mRNA.
DR EMBL; CH471058; EAX10966.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX10974.1; -; Genomic_DNA.
DR EMBL; BC022480; AAH22480.1; -; mRNA.
DR CCDS; CCDS2285.1; -. [P54750-4]
DR CCDS; CCDS33344.1; -. [P54750-1]
DR CCDS; CCDS58741.1; -. [P54750-2]
DR CCDS; CCDS74612.1; -. [P54750-3]
DR CCDS; CCDS86900.1; -. [P54750-6]
DR PIR; T14783; T14783.
DR RefSeq; NP_001003683.1; NM_001003683.2. [P54750-1]
DR RefSeq; NP_001245242.1; NM_001258313.1. [P54750-2]
DR RefSeq; NP_001245243.1; NM_001258314.1. [P54750-3]
DR RefSeq; NP_005010.2; NM_005019.4. [P54750-4]
DR RefSeq; XP_016859784.1; XM_017004295.1. [P54750-4]
DR RefSeq; XP_016859785.1; XM_017004296.1. [P54750-4]
DR RefSeq; XP_016859786.1; XM_017004297.1. [P54750-4]
DR RefSeq; XP_016859787.1; XM_017004298.1. [P54750-4]
DR RefSeq; XP_016859788.1; XM_017004299.1. [P54750-1]
DR RefSeq; XP_016859789.1; XM_017004300.1. [P54750-1]
DR RefSeq; XP_016859790.1; XM_017004301.1. [P54750-1]
DR RefSeq; XP_016859791.1; XM_017004302.1.
DR AlphaFoldDB; P54750; -.
DR SMR; P54750; -.
DR BioGRID; 111162; 5.
DR IntAct; P54750; 3.
DR STRING; 9606.ENSP00000410309; -.
DR BindingDB; P54750; -.
DR ChEMBL; CHEMBL3421; -.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB09283; Trapidil.
DR DrugCentral; P54750; -.
DR GuidetoPHARMACOLOGY; 1294; -.
DR iPTMnet; P54750; -.
DR PhosphoSitePlus; P54750; -.
DR BioMuta; PDE1A; -.
DR DMDM; 1705942; -.
DR EPD; P54750; -.
DR jPOST; P54750; -.
DR MassIVE; P54750; -.
DR MaxQB; P54750; -.
DR PaxDb; P54750; -.
DR PeptideAtlas; P54750; -.
DR PRIDE; P54750; -.
DR ProteomicsDB; 56702; -. [P54750-1]
DR ProteomicsDB; 56703; -. [P54750-2]
DR ProteomicsDB; 56704; -. [P54750-3]
DR ProteomicsDB; 56705; -. [P54750-4]
DR ProteomicsDB; 56706; -. [P54750-5]
DR ProteomicsDB; 56707; -. [P54750-6]
DR ProteomicsDB; 56708; -. [P54750-7]
DR ProteomicsDB; 56709; -. [P54750-8]
DR ProteomicsDB; 56710; -. [P54750-9]
DR Antibodypedia; 19750; 280 antibodies from 35 providers.
DR DNASU; 5136; -.
DR Ensembl; ENST00000351439.9; ENSP00000309269.9; ENSG00000115252.18. [P54750-2]
DR Ensembl; ENST00000358139.6; ENSP00000350858.3; ENSG00000115252.18. [P54750-3]
DR Ensembl; ENST00000409365.5; ENSP00000386767.1; ENSG00000115252.18. [P54750-6]
DR Ensembl; ENST00000410103.1; ENSP00000387037.1; ENSG00000115252.18. [P54750-1]
DR Ensembl; ENST00000435564.5; ENSP00000410309.1; ENSG00000115252.18. [P54750-4]
DR GeneID; 5136; -.
DR KEGG; hsa:5136; -.
DR MANE-Select; ENST00000409365.6; ENSP00000386767.1; NM_001363871.4; NP_001350800.1. [P54750-6]
DR UCSC; uc002uoq.3; human. [P54750-1]
DR CTD; 5136; -.
DR DisGeNET; 5136; -.
DR GeneCards; PDE1A; -.
DR HGNC; HGNC:8774; PDE1A.
DR HPA; ENSG00000115252; Tissue enhanced (kidney, thyroid gland).
DR MIM; 171890; gene.
DR neXtProt; NX_P54750; -.
DR OpenTargets; ENSG00000115252; -.
DR PharmGKB; PA33122; -.
DR VEuPathDB; HostDB:ENSG00000115252; -.
DR eggNOG; KOG3688; Eukaryota.
DR GeneTree; ENSGT00940000157043; -.
DR HOGENOM; CLU_005940_1_3_1; -.
DR OMA; LFRRSNM; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; P54750; -.
DR TreeFam; TF314638; -.
DR BRENDA; 3.1.4.17; 2681.
DR PathwayCommons; P54750; -.
DR Reactome; R-HSA-111957; Cam-PDE 1 activation.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SignaLink; P54750; -.
DR SIGNOR; P54750; -.
DR BioGRID-ORCS; 5136; 12 hits in 1064 CRISPR screens.
DR ChiTaRS; PDE1A; human.
DR GeneWiki; PDE1A; -.
DR GenomeRNAi; 5136; -.
DR Pharos; P54750; Tclin.
DR PRO; PR:P54750; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P54750; protein.
DR Bgee; ENSG00000115252; Expressed in sperm and 167 other tissues.
DR Genevisible; P54750; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0004117; F:calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
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; Hydrolase; Magnesium;
KW Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..535
FT /note="Dual specificity calcium/calmodulin-dependent 3',5'-
FT cyclic nucleotide phosphodiesterase 1A"
FT /id="PRO_0000198785"
FT DOMAIN 142..522
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 24..44
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P14100"
FT REGION 114..137
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P14100"
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..72
FT /note="MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGILRCLVKQLERGDVNVVDL
FT KKNIEYAASVLEAVYIDETR -> MGKKINKLFCFNFLVQCFRGKSKPSKCQIRKKVKN
FT HIE (in isoform 3, isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004548"
FT VAR_SEQ 1..34
FT /note="MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGI -> MDDHVTIRKKHLQR
FT PIFR (in isoform 2, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:11747989,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_004547"
FT VAR_SEQ 522..535
FT /note="EARTSSQKCEFIHQ -> GESDLHKNSEDLVNAEEKHDETHS (in
FT isoform 4, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004549"
FT VAR_SEQ 522..535
FT /note="EARTSSQKCEFIHQ -> GSVVYEALLPSLSVFTSPLRVWITSSRFLLL
FT (in isoform 5, isoform 7 and isoform 9)"
FT /evidence="ECO:0000305"
FT /id="VSP_004550"
SQ SEQUENCE 535 AA; 61252 MW; B1878145160BB3D7 CRC64;
MGSSATEIEE LENTTFKYLT GEQTEKMWQR LKGILRCLVK QLERGDVNVV DLKKNIEYAA
SVLEAVYIDE TRRLLDTEDE LSDIQTDSVP SEVRDWLAST FTRKMGMTKK KPEEKPKFRS
IVHAVQAGIF VERMYRKTYH MVGLAYPAAV IVTLKDVDKW SFDVFALNEA SGEHSLKFMI
YELFTRYDLI NRFKIPVSCL ITFAEALEVG YSKYKNPYHN LIHAADVTQT VHYIMLHTGI
MHWLTELEIL AMVFAAAIHD YEHTGTTNNF HIQTRSDVAI LYNDRSVLEN HHVSAAYRLM
QEEEMNILIN LSKDDWRDLR NLVIEMVLST DMSGHFQQIK NIRNSLQQPE GIDRAKTMSL
ILHAADISHP AKSWKLHYRW TMALMEEFFL QGDKEAELGL PFSPLCDRKS TMVAQSQIGF
IDFIVEPTFS LLTDSTEKIV IPLIEEASKA ETSSYVASSS TTIVGLHIAD ALRRSNTKGS
MSDGSYSPDY SLAAVDLKSF KNNLVDIIQQ NKERWKELAA QEARTSSQKC EFIHQ
