ID PDE1C_HUMAN Reviewed; 709 AA. AC Q14123; B3KPC6; E9PE92; Q14124; Q8NB10; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 11-NOV-2015, entry version 138. DE RecName: Full=Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C; DE Short=Cam-PDE 1C; DE EC=3.1.4.17; DE AltName: Full=hCam-3; GN Name=PDE1C; 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] (ISOFORMS PDE1C1 AND PDE1C2). RC TISSUE=Heart; 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 [LARGE SCALE MRNA] (ISOFORMS PDE1C2 AND 3). RC TISSUE=Heart; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). 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 high CC affinity for both cAMP and cGMP. 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=3; CC Comment=Additional isoforms seem to exist.; CC Name=PDE1C2; Synonyms=HCam-3A; CC IsoId=Q14123-1; Sequence=Displayed; CC Name=PDE1C1; Synonyms=HCam-3B; CC IsoId=Q14123-2; Sequence=VSP_004552, VSP_004553; CC Name=3; CC IsoId=Q14123-3; Sequence=VSP_044468; CC Note=No experimental confirmation available. Ref.2 (BAC03734) CC sequence is in conflict in position: 4:A->V. {ECO:0000305}; CC -!- TISSUE SPECIFICITY: Expressed in several tissues, including brain CC 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; U40371; AAC50437.1; -; mRNA. DR EMBL; U40372; AAA96961.1; -; mRNA. DR EMBL; AK056170; BAG51638.1; -; mRNA. DR EMBL; AK091734; BAC03734.1; -; mRNA. DR EMBL; AC004931; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005589; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006377; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC007033; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC007093; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018637; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS5437.1; -. [Q14123-2] DR CCDS; CCDS55099.1; -. [Q14123-1] DR CCDS; CCDS55100.1; -. [Q14123-3] DR RefSeq; NP_001177985.1; NM_001191056.2. [Q14123-2] DR RefSeq; NP_001177986.1; NM_001191057.2. [Q14123-1] DR RefSeq; NP_001177987.2; NM_001191058.2. DR RefSeq; NP_001177988.1; NM_001191059.2. [Q14123-1] DR RefSeq; NP_005011.1; NM_005020.3. [Q14123-2] DR UniGene; Hs.290550; -. DR UniGene; Hs.728862; -. DR PDB; 1LXS; Model; -; A=163-460. DR PDBsum; 1LXS; -. DR ProteinModelPortal; Q14123; -. DR SMR; Q14123; 88-455. DR BioGrid; 111163; 3. DR STRING; 9606.ENSP00000379496; -. DR BindingDB; Q14123; -. DR ChEMBL; CHEMBL2097161; -. DR DrugBank; DB00201; Caffeine. DR GuidetoPHARMACOLOGY; 1296; -. DR PhosphoSite; Q14123; -. DR BioMuta; PDE1C; -. DR DMDM; 2499445; -. DR MaxQB; Q14123; -. DR PaxDb; Q14123; -. DR PRIDE; Q14123; -. DR DNASU; 5137; -. DR Ensembl; ENST00000321453; ENSP00000318105; ENSG00000154678. [Q14123-1] DR Ensembl; ENST00000396182; ENSP00000379485; ENSG00000154678. [Q14123-2] DR Ensembl; ENST00000396184; ENSP00000379487; ENSG00000154678. [Q14123-2] DR Ensembl; ENST00000396191; ENSP00000379494; ENSG00000154678. [Q14123-1] DR GeneID; 5137; -. DR KEGG; hsa:5137; -. DR UCSC; uc003tcm.2; human. [Q14123-1] DR UCSC; uc003tco.2; human. [Q14123-3] DR UCSC; uc003tcr.3; human. [Q14123-2] DR CTD; 5137; -. DR GeneCards; PDE1C; -. DR HGNC; HGNC:8776; PDE1C. DR HPA; HPA021751; -. DR HPA; HPA052375; -. DR MIM; 602987; gene. DR neXtProt; NX_Q14123; -. DR PharmGKB; PA33124; -. DR eggNOG; KOG3688; Eukaryota. DR eggNOG; ENOG410XQDD; LUCA. DR GeneTree; ENSGT00760000118889; -. DR HOGENOM; HOG000231888; -. DR HOVERGEN; HBG056120; -. DR KO; K13755; -. DR OrthoDB; EOG7X9G6J; -. DR PhylomeDB; Q14123; -. DR TreeFam; TF314638; -. DR BRENDA; 3.1.4.17; 2681. DR Reactome; R-HSA-111957; Cam-PDE 1 activation. DR ChiTaRS; PDE1C; human. DR GeneWiki; PDE1C; -. DR GenomeRNAi; 5137; -. DR NextBio; 19808; -. DR PRO; PR:Q14123; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; Q14123; -. DR CleanEx; HS_PDE1C; -. DR ExpressionAtlas; Q14123; baseline and differential. DR Genevisible; Q14123; 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: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 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calmodulin-binding; KW cAMP; cGMP; Complete proteome; Hydrolase; Metal-binding; KW Reference proteome. FT CHAIN 1 709 Calcium/calmodulin-dependent 3',5'-cyclic FT nucleotide phosphodiesterase 1C. FT /FTId=PRO_0000198792. FT REGION 202 521 Catalytic. {ECO:0000250}. FT ACT_SITE 228 228 Proton donor. {ECO:0000250}. FT METAL 232 232 Divalent metal cation 1. {ECO:0000250}. FT METAL 268 268 Divalent metal cation 1. {ECO:0000250}. FT METAL 269 269 Divalent metal cation 1. {ECO:0000250}. FT METAL 269 269 Divalent metal cation 2. {ECO:0000250}. FT METAL 376 376 Divalent metal cation 1. {ECO:0000250}. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:19369195}. FT VAR_SEQ 1 38 MESPTKEIEEFESNSLKYLQPEQIEKIWLRLRGLRKYK -> FT MTDAGNRKEGFKKCRSATFSIDGYSFTIVANEAGDKNARPL FT ARFSRSKSQNCLWNSLIDGLTGNVKEKPRPTIVHDPRPPEE FT ILADELPQLDSSEVLV (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044468. FT VAR_SEQ 631 634 GTKQ -> DSQE (in isoform PDE1C1). FT {ECO:0000303|PubMed:8557689}. FT /FTId=VSP_004552. FT VAR_SEQ 635 709 Missing (in isoform PDE1C1). FT {ECO:0000303|PubMed:8557689}. FT /FTId=VSP_004553. FT CONFLICT 42 42 Q -> F (in Ref. 2; BAC03734). FT {ECO:0000305}. FT CONFLICT 126 126 R -> L (in Ref. 2; BAC03734). FT {ECO:0000305}. SQ SEQUENCE 709 AA; 80760 MW; 77133D4DDBE5F7C0 CRC64; MESPTKEIEE FESNSLKYLQ PEQIEKIWLR LRGLRKYKKT SQRLRSLVKQ LERGEASVVD LKKNLEYAAT VLESVYIDET RRLLDTEDEL SDIQSDAVPS EVRDWLASTF TRQMGMMLRR SDEKPRFKSI VHAVQAGIFV ERMYRRTSNM VGLSYPPAVI EALKDVDKWS FDVFSLNEAS GDHALKFIFY ELLTRYDLIS RFKIPISALV SFVEALEVGY SKHKNPYHNL MHAADVTQTV HYLLYKTGVA NWLTELEIFA IIFSAAIHDY EHTGTTNNFH IQTRSDPAIL YNDRSVLENH HLSAAYRLLQ DDEEMNILIN LSKDDWREFR TLVIEMVMAT DMSCHFQQIK AMKTALQQPE AIEKPKALSL MLHTADISHP AKAWDLHHRW TMSLLEEFFR QGDREAELGL PFSPLCDRKS TMVAQSQVGF IDFIVEPTFT VLTDMTEKIV SPLIDETSQT GGTGQRRSSL NSISSSDAKR SGVKTSGSEG SAPINNSVIS VDYKSFKATW TEVVHINRER WRAKVPKEEK AKKEAEEKAR LAAEEQQKEM EAKSQAEEGA SGKAEKKTSG ETKNQVNGTR ANKSDNPRGK NSKAEKSSGE QQQNGDFKDG KNKTDKKDHS NIGNDSKKTD GTKQRSHGSP APSTSSTCRL TLPVIKPPLR HFKRPAYASS SYAPSVSKKT DEHPARYKML DQRIKMKKIQ NISHNWNRK //