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Database: UniProt
Entry: O76074
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Original site: O76074 
ID   PDE5A_HUMAN             Reviewed;         875 AA.
AC   O76074; A0AV69; A8K2C4; O75026; O75887; Q86UI0; Q86V66; Q9Y6Z6;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   26-NOV-2014, entry version 147.
DE   RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase;
DE            EC=3.1.4.35;
DE   AltName: Full=cGMP-binding cGMP-specific phosphodiesterase;
DE            Short=CGB-PDE;
GN   Name=PDE5A; Synonyms=PDE5;
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 PDE5A1 AND PDE5A2), AND VARIANT
RP   VAL-93.
RX   PubMed=9714779; DOI=10.1016/S0378-1119(98)00303-5;
RA   Loughney K., Hill T.R., Florio V.A., Uher L., Rosman G.J., Wolda S.L.,
RA   Jones B.A., Howard M.L., McAllister-Lucas L.M., Sonnenburg W.K.,
RA   Francis S.H., Corbin J.D., Beavo J.A., Ferguson K.;
RT   "Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-
RT   binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.";
RL   Gene 216:139-147(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM PDE5A1), AND VARIANT
RP   VAL-93.
RC   TISSUE=Lung, and Placenta;
RX   PubMed=9716380; DOI=10.1046/j.1432-1327.1998.2550391.x;
RA   Yanaka N., Kotera J., Ohtsuka A., Akatsuka H., Imai Y., Michibata H.,
RA   Fujishige K., Kawai E., Takebayashi S., Okumura K., Omori K.;
RT   "Expression, structure and chromosomal localization of the human cGMP-
RT   binding cGMP-specific phosphodiesterase PDE5A gene.";
RL   Eur. J. Biochem. 255:391-399(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A1), AND VARIANT VAL-93.
RC   TISSUE=Prostate, and Skeletal muscle;
RX   PubMed=9642111; DOI=10.1006/bbrc.1998.8769;
RA   Stacey P., Rulten S., Dapling A., Phillips S.C.;
RT   "Molecular cloning and expression of human cGMP-binding cGMP-specific
RT   phosphodiesterase.";
RL   Biochem. Biophys. Res. Commun. 247:249-254(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A2), AND VARIANT VAL-93.
RC   TISSUE=Lung;
RA   Kotera J., Imai Y., Omori K.;
RT   "Molecular cloning and characterization of human cGMP-specific
RT   phosphodiesterase 5A2 cDNA.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE5A2).
RC   TISSUE=Colon carcinoma;
RA   Sopory S., Visweswariah S.S.;
RT   "PDE5A splice variants in T84 cells.";
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE5A1), AND VARIANT
RP   VAL-93.
RC   TISSUE=Thalamus;
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE5A1).
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).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 157-411.
RC   TISSUE=Trabecular meshwork;
RX   PubMed=10393044;
RA   Zhou L., Thompson W.J., Potter D.E.;
RT   "Multiple cyclic nucleotide phosphodiesterases in human trabecular
RT   meshwork cells.";
RL   Invest. Ophthalmol. Vis. Sci. 40:1745-1752(1999).
RN   [10]
RP   PHOSPHORYLATION BY PRKG1.
RX   PubMed=11723116; DOI=10.1074/jbc.M106562200;
RA   Rybalkin S.D., Rybalkina I.G., Feil R., Hofmann F., Beavo J.A.;
RT   "Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation
RT   in smooth muscle cells.";
RL   J. Biol. Chem. 277:3310-3317(2002).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 537-860 IN COMPLEX WITH THE
RP   INHIBITORS SILDENAFIL; TADALAFIL AND VARDENAFIL, AND METAL-BINDING.
RX   PubMed=12955149; DOI=10.1038/nature01914;
RA   Sung B.-J., Hwang K.Y., Jeon Y.H., Lee J.I., Heo Y.-S., Kim J.H.,
RA   Moon J., Yoon J.M., Hyun Y.-L., Kim E., Eum S.J., Park S.-Y.,
RA   Lee J.-O., Lee T.G., Ro S., Cho J.M.;
RT   "Structure of the catalytic domain of human phosphodiesterase 5 with
RT   bound drug molecules.";
RL   Nature 425:98-102(2003).
CC   -!- FUNCTION: Plays a role in signal transduction by regulating the
CC       intracellular concentration of cyclic nucleotides. This
CC       phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-
CC       GMP.
CC   -!- CATALYTIC ACTIVITY: Guanosine 3',5'-cyclic phosphate + H(2)O =
CC       guanosine 5'-phosphate.
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
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.;
CC   -!- ENZYME REGULATION: Sildenafil (Viagra) is a highly selective and
CC       potent inhibitor of PDE5A and is effective in the treatment of
CC       penile erectile dysfunction. Also inhibited by zaprinast.
CC   -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC       3',5'-cyclic GMP: step 1/1.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=PDE5A1;
CC         IsoId=O76074-1; Sequence=Displayed;
CC       Name=PDE5A2;
CC         IsoId=O76074-2; Sequence=VSP_004591;
CC   -!- TISSUE SPECIFICITY: Expressed in aortic smooth muscle cells,
CC       heart, placenta, skeletal muscle and pancreas and, to a much
CC       lesser extent, in brain, liver and lung.
CC   -!- DOMAIN: Composed of a C-terminal catalytic domain containing two
CC       putative divalent metal sites and an N-terminal regulatory domain
CC       which contains two homologous allosteric cGMP-binding regions, A
CC       and B.
CC   -!- PTM: Phosphorylation is regulated by binding of cGMP to the two
CC       allosteric sites (By similarity). Phosphorylation by PRKG1 leads
CC       to its activation. {ECO:0000250, ECO:0000269|PubMed:11723116}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 2 GAF domains. {ECO:0000305}.
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DR   EMBL; AF043731; AAC63967.1; -; mRNA.
DR   EMBL; AF043732; AAC63968.1; -; mRNA.
DR   EMBL; AB001635; BAA33372.2; -; Genomic_DNA.
DR   EMBL; D89094; BAA28945.1; -; mRNA.
DR   EMBL; AJ004865; CAA06170.1; -; mRNA.
DR   EMBL; AB015656; BAA81667.1; -; mRNA.
DR   EMBL; AY264918; AAP21809.1; -; mRNA.
DR   EMBL; AK290189; BAF82878.1; -; mRNA.
DR   EMBL; AC093752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC080089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC126233; AAI26234.1; -; mRNA.
DR   EMBL; AY266363; AAP31235.1; -; mRNA.
DR   CCDS; CCDS34055.1; -. [O76074-2]
DR   CCDS; CCDS3713.1; -. [O76074-1]
DR   PIR; JW0106; JW0106.
DR   RefSeq; NP_001074.2; NM_001083.3. [O76074-1]
DR   RefSeq; NP_236914.2; NM_033430.2. [O76074-2]
DR   RefSeq; NP_246273.2; NM_033437.3.
DR   UniGene; Hs.647971; -.
DR   PDB; 1RKP; X-ray; 2.05 A; A=535-860.
DR   PDB; 1T9R; X-ray; 2.10 A; A=531-875.
DR   PDB; 1T9S; X-ray; 2.00 A; A/B=534-858.
DR   PDB; 1TBF; X-ray; 1.30 A; A=534-858.
DR   PDB; 1UDT; X-ray; 2.30 A; A=537-860.
DR   PDB; 1UDU; X-ray; 2.83 A; A/B=537-860.
DR   PDB; 1UHO; X-ray; 2.50 A; A=537-860.
DR   PDB; 1XOZ; X-ray; 1.37 A; A=534-875.
DR   PDB; 1XP0; X-ray; 1.79 A; A=534-875.
DR   PDB; 2CHM; X-ray; 1.60 A; A=534-656, A=682-858.
DR   PDB; 2H40; X-ray; 1.85 A; A=535-860.
DR   PDB; 2H42; X-ray; 2.30 A; A/B/C=535-860.
DR   PDB; 2H44; X-ray; 1.80 A; A=535-860.
DR   PDB; 2XSS; X-ray; 2.50 A; A/B=346-509.
DR   PDB; 3B2R; X-ray; 2.07 A; A/B=535-860.
DR   PDB; 3BJC; X-ray; 2.00 A; A=1-875.
DR   PDB; 3HC8; X-ray; 1.79 A; A=536-657, A=682-858.
DR   PDB; 3HDZ; X-ray; 1.80 A; A=536-657, A=682-858.
DR   PDB; 3JWQ; X-ray; 2.87 A; A/B/C/D=535-786, A/B/C/D=827-860.
DR   PDB; 3JWR; X-ray; 2.99 A; A/B=535-786, A/B=827-860.
DR   PDB; 3LFV; X-ray; 2.80 A; A/B=98-518.
DR   PDB; 3MF0; X-ray; 3.10 A; A/B=89-518.
DR   PDB; 3SHY; X-ray; 2.65 A; A=535-860.
DR   PDB; 3SHZ; X-ray; 2.45 A; A=535-860.
DR   PDB; 3SIE; X-ray; 1.93 A; A/B=535-860.
DR   PDB; 3TGE; X-ray; 1.96 A; A=534-656, A=682-858.
DR   PDB; 3TGG; X-ray; 1.91 A; A=534-660, A=662-858.
DR   PDB; 3TSE; X-ray; 2.14 A; A=535-860.
DR   PDB; 3TSF; X-ray; 2.44 A; A=535-860.
DR   PDB; 4G2W; X-ray; 2.28 A; A=535-860.
DR   PDB; 4G2Y; X-ray; 2.40 A; A=535-860.
DR   PDB; 4I9Z; X-ray; 2.08 A; A=535-860.
DR   PDB; 4IA0; X-ray; 2.17 A; A=535-860.
DR   PDB; 4MD6; X-ray; 2.00 A; A=535-860.
DR   PDBsum; 1RKP; -.
DR   PDBsum; 1T9R; -.
DR   PDBsum; 1T9S; -.
DR   PDBsum; 1TBF; -.
DR   PDBsum; 1UDT; -.
DR   PDBsum; 1UDU; -.
DR   PDBsum; 1UHO; -.
DR   PDBsum; 1XOZ; -.
DR   PDBsum; 1XP0; -.
DR   PDBsum; 2CHM; -.
DR   PDBsum; 2H40; -.
DR   PDBsum; 2H42; -.
DR   PDBsum; 2H44; -.
DR   PDBsum; 2XSS; -.
DR   PDBsum; 3B2R; -.
DR   PDBsum; 3BJC; -.
DR   PDBsum; 3HC8; -.
DR   PDBsum; 3HDZ; -.
DR   PDBsum; 3JWQ; -.
DR   PDBsum; 3JWR; -.
DR   PDBsum; 3LFV; -.
DR   PDBsum; 3MF0; -.
DR   PDBsum; 3SHY; -.
DR   PDBsum; 3SHZ; -.
DR   PDBsum; 3SIE; -.
DR   PDBsum; 3TGE; -.
DR   PDBsum; 3TGG; -.
DR   PDBsum; 3TSE; -.
DR   PDBsum; 3TSF; -.
DR   PDBsum; 4G2W; -.
DR   PDBsum; 4G2Y; -.
DR   PDBsum; 4I9Z; -.
DR   PDBsum; 4IA0; -.
DR   PDBsum; 4MD6; -.
DR   ProteinModelPortal; O76074; -.
DR   SMR; O76074; 98-860.
DR   BioGrid; 114205; 1.
DR   DIP; DIP-46287N; -.
DR   STRING; 9606.ENSP00000347046; -.
DR   BindingDB; O76074; -.
DR   ChEMBL; CHEMBL2111400; -.
DR   DrugBank; DB06237; Avanafil.
DR   DrugBank; DB00201; Caffeine.
DR   DrugBank; DB00975; Dipyridamole.
DR   DrugBank; DB00806; Pentoxifylline.
DR   DrugBank; DB00203; Sildenafil.
DR   DrugBank; DB00820; Tadalafil.
DR   DrugBank; DB00277; Theophylline.
DR   DrugBank; DB06267; Udenafil.
DR   DrugBank; DB00862; Vardenafil.
DR   GuidetoPHARMACOLOGY; 1304; -.
DR   PhosphoSite; O76074; -.
DR   MaxQB; O76074; -.
DR   PaxDb; O76074; -.
DR   PRIDE; O76074; -.
DR   DNASU; 8654; -.
DR   Ensembl; ENST00000264805; ENSP00000264805; ENSG00000138735. [O76074-2]
DR   Ensembl; ENST00000354960; ENSP00000347046; ENSG00000138735. [O76074-1]
DR   GeneID; 8654; -.
DR   KEGG; hsa:8654; -.
DR   UCSC; uc003idf.3; human. [O76074-2]
DR   UCSC; uc003idg.3; human. [O76074-1]
DR   CTD; 8654; -.
DR   GeneCards; GC04M120415; -.
DR   HGNC; HGNC:8784; PDE5A.
DR   HPA; HPA004729; -.
DR   HPA; HPA012873; -.
DR   MIM; 603310; gene.
DR   neXtProt; NX_O76074; -.
DR   PharmGKB; PA33132; -.
DR   eggNOG; NOG270709; -.
DR   GeneTree; ENSGT00760000119066; -.
DR   HOVERGEN; HBG101207; -.
DR   KO; K13762; -.
DR   OMA; REHDANK; -.
DR   OrthoDB; EOG7RRF69; -.
DR   PhylomeDB; O76074; -.
DR   TreeFam; TF316499; -.
DR   BRENDA; 3.1.4.35; 2681.
DR   Reactome; REACT_23767; cGMP effects.
DR   UniPathway; UPA00763; UER00748.
DR   ChiTaRS; PDE5A; human.
DR   EvolutionaryTrace; O76074; -.
DR   GeneWiki; CGMP-specific_phosphodiesterase_type_5; -.
DR   GenomeRNAi; 8654; -.
DR   NextBio; 32453; -.
DR   PRO; PR:O76074; -.
DR   Bgee; O76074; -.
DR   CleanEx; HS_PDE5A; -.
DR   ExpressionAtlas; O76074; baseline and differential.
DR   Genevestigator; O76074; -.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; NAS:UniProtKB.
DR   GO; GO:0030553; F:cGMP binding; TAS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0046069; P:cGMP catabolic process; IDA:UniProtKB.
DR   GO; GO:0055118; P:negative regulation of cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR   GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IEA:Ensembl.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR   GO; GO:0060282; P:positive regulation of oocyte development; IEA:Ensembl.
DR   GO; GO:0055119; P:relaxation of cardiac muscle; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   Gene3D; 1.10.1300.10; -; 1.
DR   Gene3D; 3.30.450.40; -; 2.
DR   InterPro; IPR003018; GAF.
DR   InterPro; IPR029016; GAF_dom_like.
DR   InterPro; IPR003607; HD/PDEase_dom.
DR   InterPro; IPR023088; PDEase.
DR   InterPro; IPR002073; PDEase_catalytic_dom.
DR   InterPro; IPR023174; PDEase_CS.
DR   Pfam; PF01590; GAF; 2.
DR   Pfam; PF00233; PDEase_I; 1.
DR   PRINTS; PR00387; PDIESTERASE1.
DR   SMART; SM00065; GAF; 2.
DR   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF55781; SSF55781; 2.
DR   PROSITE; PS00126; PDEASE_I; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Allosteric enzyme; Alternative splicing; cGMP;
KW   cGMP-binding; Complete proteome; Hydrolase; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW   Repeat.
FT   CHAIN         1    875       cGMP-specific 3',5'-cyclic
FT                                phosphodiesterase.
FT                                /FTId=PRO_0000198823.
FT   DOMAIN      164    314       GAF 1.
FT   DOMAIN      346    503       GAF 2.
FT   REGION      588    853       Catalytic. {ECO:0000250}.
FT   COMPBIAS     10     24       Poly-Gln.
FT   ACT_SITE    613    613       Proton donor. {ECO:0000250}.
FT   METAL       617    617       Divalent metal cation 1.
FT   METAL       653    653       Divalent metal cation 1.
FT   METAL       654    654       Divalent metal cation 1.
FT   METAL       654    654       Divalent metal cation 2.
FT   METAL       764    764       Divalent metal cation 1.
FT   BINDING     817    817       cGMP.
FT   MOD_RES     102    102       Phosphoserine. {ECO:0000255}.
FT   VAR_SEQ       1     49       MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFT
FT                                FSYFVRKA -> MLPFGDK (in isoform PDE5A2).
FT                                {ECO:0000303|PubMed:9714779,
FT                                ECO:0000303|Ref.4, ECO:0000303|Ref.5}.
FT                                /FTId=VSP_004591.
FT   VARIANT      93     93       A -> V (in dbSNP:rs3733526).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|PubMed:9642111,
FT                                ECO:0000269|PubMed:9714779,
FT                                ECO:0000269|PubMed:9716380,
FT                                ECO:0000269|Ref.4}.
FT                                /FTId=VAR_027775.
FT   VARIANT     181    181       S -> A (in dbSNP:rs17051276).
FT                                /FTId=VAR_027776.
FT   CONFLICT    159    159       I -> V (in Ref. 9; AAP31235).
FT                                {ECO:0000305}.
FT   CONFLICT    310    310       C -> G (in Ref. 9; AAP31235).
FT                                {ECO:0000305}.
FT   CONFLICT    381    381       S -> F (in Ref. 9; AAP31235).
FT                                {ECO:0000305}.
FT   CONFLICT    406    406       K -> R (in Ref. 9; AAP31235).
FT                                {ECO:0000305}.
FT   CONFLICT    642    642       E -> G (in Ref. 4; BAA81667).
FT                                {ECO:0000305}.
FT   HELIX       103    106       {ECO:0000244|PDB:3LFV}.
FT   STRAND      115    117       {ECO:0000244|PDB:3LFV}.
FT   TURN        118    120       {ECO:0000244|PDB:3LFV}.
FT   STRAND      121    124       {ECO:0000244|PDB:3LFV}.
FT   HELIX       148    160       {ECO:0000244|PDB:3LFV}.
FT   HELIX       165    177       {ECO:0000244|PDB:3LFV}.
FT   STRAND      182    192       {ECO:0000244|PDB:3LFV}.
FT   STRAND      198    205       {ECO:0000244|PDB:3LFV}.
FT   STRAND      208    210       {ECO:0000244|PDB:3MF0}.
FT   STRAND      213    218       {ECO:0000244|PDB:3LFV}.
FT   STRAND      221    224       {ECO:0000244|PDB:3LFV}.
FT   HELIX       228    236       {ECO:0000244|PDB:3LFV}.
FT   STRAND      240    243       {ECO:0000244|PDB:3LFV}.
FT   HELIX       245    247       {ECO:0000244|PDB:3LFV}.
FT   HELIX       254    259       {ECO:0000244|PDB:3LFV}.
FT   STRAND      266    272       {ECO:0000244|PDB:3LFV}.
FT   STRAND      278    287       {ECO:0000244|PDB:3LFV}.
FT   HELIX       299    340       {ECO:0000244|PDB:3LFV}.
FT   TURN        342    345       {ECO:0000244|PDB:3MF0}.
FT   HELIX       346    362       {ECO:0000244|PDB:2XSS}.
FT   STRAND      365    372       {ECO:0000244|PDB:2XSS}.
FT   STRAND      374    376       {ECO:0000244|PDB:3LFV}.
FT   STRAND      379    387       {ECO:0000244|PDB:2XSS}.
FT   TURN        388    390       {ECO:0000244|PDB:3LFV}.
FT   STRAND      391    393       {ECO:0000244|PDB:3LFV}.
FT   HELIX       400    403       {ECO:0000244|PDB:2XSS}.
FT   HELIX       407    409       {ECO:0000244|PDB:2XSS}.
FT   HELIX       410    418       {ECO:0000244|PDB:2XSS}.
FT   STRAND      422    425       {ECO:0000244|PDB:2XSS}.
FT   TURN        427    429       {ECO:0000244|PDB:2XSS}.
FT   STRAND      431    433       {ECO:0000244|PDB:3LFV}.
FT   STRAND      451    457       {ECO:0000244|PDB:2XSS}.
FT   STRAND      461    471       {ECO:0000244|PDB:2XSS}.
FT   TURN        476    478       {ECO:0000244|PDB:3LFV}.
FT   HELIX       486    506       {ECO:0000244|PDB:2XSS}.
FT   HELIX       535    545       {ECO:0000244|PDB:1TBF}.
FT   HELIX       551    554       {ECO:0000244|PDB:1TBF}.
FT   TURN        555    557       {ECO:0000244|PDB:1TBF}.
FT   HELIX       568    581       {ECO:0000244|PDB:1TBF}.
FT   HELIX       584    587       {ECO:0000244|PDB:1TBF}.
FT   HELIX       592    604       {ECO:0000244|PDB:1TBF}.
FT   TURN        606    608       {ECO:0000244|PDB:1T9R}.
FT   STRAND      610    614       {ECO:0000244|PDB:1TBF}.
FT   HELIX       615    630       {ECO:0000244|PDB:1TBF}.
FT   TURN        631    633       {ECO:0000244|PDB:1UHO}.
FT   HELIX       635    637       {ECO:0000244|PDB:1TBF}.
FT   HELIX       640    652       {ECO:0000244|PDB:1TBF}.
FT   TURN        653    656       {ECO:0000244|PDB:1TBF}.
FT   HELIX       662    667       {ECO:0000244|PDB:1TBF}.
FT   HELIX       671    675       {ECO:0000244|PDB:1TBF}.
FT   STRAND      677    679       {ECO:0000244|PDB:3JWQ}.
FT   HELIX       680    694       {ECO:0000244|PDB:1TBF}.
FT   TURN        700    703       {ECO:0000244|PDB:1TBF}.
FT   HELIX       706    722       {ECO:0000244|PDB:1TBF}.
FT   HELIX       725    740       {ECO:0000244|PDB:1TBF}.
FT   STRAND      746    748       {ECO:0000244|PDB:1UDU}.
FT   HELIX       749    764       {ECO:0000244|PDB:1TBF}.
FT   HELIX       766    769       {ECO:0000244|PDB:1TBF}.
FT   HELIX       772    796       {ECO:0000244|PDB:1TBF}.
FT   HELIX       803    805       {ECO:0000244|PDB:1TBF}.
FT   HELIX       807    812       {ECO:0000244|PDB:1TBF}.
FT   HELIX       813    823       {ECO:0000244|PDB:1TBF}.
FT   HELIX       825    835       {ECO:0000244|PDB:1TBF}.
FT   HELIX       837    839       {ECO:0000244|PDB:1TBF}.
FT   HELIX       840    857       {ECO:0000244|PDB:1TBF}.
SQ   SEQUENCE   875 AA;  99985 MW;  9E30C6C182F13388 CRC64;
     MERAGPSFGQ QRQQQQPQQQ KQQQRDQDSV EAWLDDHWDF TFSYFVRKAT REMVNAWFAE
     RVHTIPVCKE GIRGHTESCS CPLQQSPRAD NSAPGTPTRK ISASEFDRPL RPIVVKDSEG
     TVSFLSDSEK KEQMPLTPPR FDHDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI
     SADRYSLFLV CEDSSNDKFL ISRLFDVAEG STLEEVSNNC IRLEWNKGIV GHVAALGEPL
     NIKDAYEDPR FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE
     KDFAAYLAFC GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS
     FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR EHDANKINYM YAQYVKNTME
     PLNIPDVSKD KRFPWTTENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK
     VKPFNRNDEQ FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL
     QSLAAAVVPS AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL
     SVKKNYRKNV AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV
     NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI
     LATDLALYIK RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE
     LVATEFFDQG DRERKELNIE PTDLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF
     PLLDGCRKNR QKWQALAEQQ EKMLINGESG QAKRN
//
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