ID PDE1A_HUMAN Reviewed; 535 AA. AC P54750; D3DPG5; Q86VZ0; Q9C0K8; Q9C0K9; Q9C0L0; Q9C0L1; Q9C0L2; AC Q9C0L3; Q9C0L4; Q9UFX3; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 163. DE RecName: Full=Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A; DE Short=Cam-PDE 1A; DE EC=3.1.4.17; DE AltName: Full=61 kDa Cam-PDE; DE AltName: Full=hCam-1; GN Name=PDE1A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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 RT chromosomal 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 RT encoding 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: Cyclic nucleotide phosphodiesterase with a dual- CC specificity for the second messengers cAMP and cGMP, which are key CC regulators of many important physiological processes. Has a higher CC affinity for cGMP than for cAMP. CC -!- CATALYTIC ACTIVITY: Nucleoside 3',5'-cyclic phosphate + H(2)O = CC nucleoside 5'-phosphate. CC -!- COFACTOR: CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; CC Evidence={ECO:0000250}; CC Note=Binds 2 divalent metal cations per subunit. Site 1 may CC preferentially bind zinc ions, while site 2 has a preference for CC magnesium and/or manganese ions. {ECO:0000250}; CC -!- ENZYME REGULATION: Type I PDE are activated by the binding of CC calmodulin in the presence of Ca(2+). CC -!- SUBUNIT: Homodimer. {ECO:0000250}. 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, CC testes and heart. CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase CC family. PDE1 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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 UniGene; Hs.191046; -. DR UniGene; Hs.742065; -. DR UniGene; Hs.742174; -. DR PDB; 1LXQ; Model; -; A=154-432. DR PDBsum; 1LXQ; -. DR ProteinModelPortal; P54750; -. DR SMR; P54750; 146-520. DR BioGrid; 111162; 4. DR IntAct; P54750; 1. DR MINT; MINT-4717501; -. DR STRING; 9606.ENSP00000331574; -. DR BindingDB; P54750; -. DR ChEMBL; CHEMBL2095150; -. DR DrugBank; DB01244; Bepridil. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB01023; Felodipine. DR DrugBank; DB00622; Nicardipine. DR GuidetoPHARMACOLOGY; 1294; -. DR PhosphoSite; P54750; -. DR BioMuta; PDE1A; -. DR DMDM; 1705942; -. DR MaxQB; P54750; -. DR PaxDb; P54750; -. DR PRIDE; P54750; -. DR DNASU; 5136; -. DR Ensembl; ENST00000351439; ENSP00000309269; ENSG00000115252. [P54750-2] DR Ensembl; ENST00000358139; ENSP00000350858; ENSG00000115252. [P54750-3] DR Ensembl; ENST00000409365; ENSP00000386767; ENSG00000115252. [P54750-6] DR Ensembl; ENST00000410103; ENSP00000387037; ENSG00000115252. [P54750-1] DR Ensembl; ENST00000435564; ENSP00000410309; ENSG00000115252. [P54750-4] DR GeneID; 5136; -. DR KEGG; hsa:5136; -. DR UCSC; uc002uoq.2; human. [P54750-4] DR UCSC; uc002uor.4; human. [P54750-2] DR UCSC; uc002uos.4; human. [P54750-1] DR UCSC; uc002uou.4; human. [P54750-3] DR CTD; 5136; -. DR GeneCards; PDE1A; -. DR HGNC; HGNC:8774; PDE1A. DR HPA; HPA022151; -. DR MIM; 171890; gene. DR neXtProt; NX_P54750; -. DR PharmGKB; PA33122; -. DR eggNOG; KOG3688; Eukaryota. DR eggNOG; ENOG410XQDD; LUCA. DR GeneTree; ENSGT00760000118889; -. DR HOVERGEN; HBG056120; -. DR KO; K13755; -. DR OMA; NRLRCLV; -. DR OrthoDB; EOG7X9G6J; -. DR PhylomeDB; P54750; -. DR TreeFam; TF314638; -. DR BRENDA; 3.1.4.17; 2681. 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 ChiTaRS; PDE1A; human. DR GeneWiki; PDE1A; -. DR GenomeRNAi; 5136; -. DR NextBio; 19802; -. DR PRO; PR:P54750; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; P54750; -. DR Genevisible; P54750; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004117; F:calmodulin-dependent cyclic-nucleotide phosphodiesterase activity; TAS:ProtInc. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:Reactome. DR Gene3D; 1.10.1300.10; -; 2. DR InterPro; IPR003607; HD/PDEase_dom. DR InterPro; IPR023088; PDEase. DR InterPro; IPR002073; PDEase_catalytic_dom. 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. PE 2: Evidence at transcript level; KW 3D-structure; Alternative splicing; Calmodulin-binding; cAMP; cGMP; KW Complete proteome; Hydrolase; Metal-binding; Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P14100}. FT CHAIN 2 535 Calcium/calmodulin-dependent 3',5'-cyclic FT nucleotide phosphodiesterase 1A. FT /FTId=PRO_0000198785. FT REGION 24 44 Calmodulin-binding. {ECO:0000250}. FT REGION 193 515 Catalytic. {ECO:0000250}. FT ACT_SITE 219 219 Proton donor. {ECO:0000250}. FT METAL 223 223 Divalent metal cation 1. {ECO:0000250}. FT METAL 259 259 Divalent metal cation 1. {ECO:0000250}. FT METAL 260 260 Divalent metal cation 1. {ECO:0000250}. FT METAL 260 260 Divalent metal cation 2. {ECO:0000250}. FT METAL 366 366 Divalent metal cation 1. {ECO:0000250}. FT VAR_SEQ 1 72 MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGILRCLVKQ FT LERGDVNVVDLKKNIEYAASVLEAVYIDETR -> MGKKIN FT KLFCFNFLVQCFRGKSKPSKCQIRKKVKNHIE (in FT isoform 3, isoform 8 and isoform 9). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_004548. FT VAR_SEQ 1 34 MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGI -> MDD FT HVTIRKKHLQRPIFR (in isoform 2, isoform 6 FT and isoform 7). FT {ECO:0000303|PubMed:11747989, FT ECO:0000303|PubMed:17974005}. FT /FTId=VSP_004547. FT VAR_SEQ 522 535 EARTSSQKCEFIHQ -> GESDLHKNSEDLVNAEEKHDETH FT S (in isoform 4, isoform 6 and isoform FT 8). {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_004549. FT VAR_SEQ 522 535 EARTSSQKCEFIHQ -> GSVVYEALLPSLSVFTSPLRVWI FT TSSRFLLL (in isoform 5, isoform 7 and FT isoform 9). {ECO:0000305}. FT /FTId=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 //