ID   PDE5A_RAT               Reviewed;         833 AA.
AC   O54735;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   08-NOV-2023, entry version 150.
DE   RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase;
DE            EC=3.1.4.35 {ECO:0000250|UniProtKB:O76074};
DE   AltName: Full=cGMP-binding cGMP-specific phosphodiesterase;
DE            Short=CGB-PDE;
GN   Name=Pde5a; Synonyms=Pde5;
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].
RC   STRAIN=Sprague-Dawley; TISSUE=Lung;
RX   PubMed=9370351; DOI=10.1111/j.1432-1033.1997.t01-1-00434.x;
RA   Kotera J., Yanaka N., Fujishige K., Imai Y., Akatsuka H., Ishizuka T.,
RA   Kawashima K., Omori K.;
RT   "Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in
RT   Purkinje cell layers during postnatal neuronal development.";
RL   Eur. J. Biochem. 249:434-442(1997).
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'-GMP.
CC       Specifically regulates nitric-oxide-generated cGMP.
CC       {ECO:0000250|UniProtKB:O76074}.
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; EC=3.1.4.35;
CC         Evidence={ECO:0000250|UniProtKB:O76074};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC         Evidence={ECO:0000250|UniProtKB:O76074};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:O76074};
CC       Note=Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per
CC       subunit: site 1 preferentially binds zinc, while site 2 has a
CC       preference for magnesium. Tightly binds zinc.
CC       {ECO:0000250|UniProtKB:O76074};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:O76074};
CC       Note=Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations
CC       per subunit: site 1 preferentially binds zinc, while site 2 has a
CC       preference for magnesium. Binds magnesium less tightly than zinc.
CC       {ECO:0000250|UniProtKB:O76074};
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=PDE5A2;
CC         IsoId=O54735-1; Sequence=Displayed;
CC       Name=PDE5A1;
CC         IsoId=O54735-2; Sequence=Not described;
CC   -!- DOMAIN: Composed of a C-terminal catalytic domain containing two
CC       putative divalent metal sites and an N-terminal regulatory domain which
CC       contains two homologous allosteric cGMP-binding regions, A and B.
CC   -!- PTM: Phosphorylation is regulated by binding of cGMP to the two
CC       allosteric sites. Phosphorylation by PRKG1 leads to its activation.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       {ECO:0000305}.
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DR   EMBL; D89093; BAA23672.1; -; mRNA.
DR   RefSeq; NP_598268.1; NM_133584.1. [O54735-1]
DR   AlphaFoldDB; O54735; -.
DR   SMR; O54735; -.
DR   STRING; 10116.ENSRNOP00000019637; -.
DR   BindingDB; O54735; -.
DR   ChEMBL; CHEMBL4567; -.
DR   DrugCentral; O54735; -.
DR   iPTMnet; O54735; -.
DR   PhosphoSitePlus; O54735; -.
DR   PaxDb; 10116-ENSRNOP00000019637; -.
DR   GeneID; 171115; -.
DR   KEGG; rno:171115; -.
DR   UCSC; RGD:620995; rat. [O54735-1]
DR   AGR; RGD:620995; -.
DR   CTD; 8654; -.
DR   RGD; 620995; Pde5a.
DR   eggNOG; KOG3689; Eukaryota.
DR   InParanoid; O54735; -.
DR   OrthoDB; 5479253at2759; -.
DR   PhylomeDB; O54735; -.
DR   BRENDA; 3.1.4.35; 5301.
DR   Reactome; R-RNO-418457; cGMP effects.
DR   Reactome; R-RNO-445355; Smooth Muscle Contraction.
DR   Reactome; R-RNO-9013422; RHOBTB1 GTPase cycle.
DR   SABIO-RK; O54735; -.
DR   UniPathway; UPA00763; UER00748.
DR   PRO; PR:O54735; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:RGD.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISO:RGD.
DR   GO; GO:0030553; F:cGMP binding; ISO:RGD.
DR   GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; ISO:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046069; P:cGMP catabolic process; ISO:RGD.
DR   GO; GO:0046068; P:cGMP metabolic process; ISO:RGD.
DR   GO; GO:0055118; P:negative regulation of cardiac muscle contraction; ISO:RGD.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR   GO; GO:0007399; P:nervous system development; IEP:RGD.
DR   GO; GO:0048599; P:oocyte development; ISO:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
DR   GO; GO:0002678; P:positive regulation of chronic inflammatory response; IMP:RGD.
DR   GO; GO:0060282; P:positive regulation of oocyte development; ISO:RGD.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR   GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; ISO:RGD.
DR   GO; GO:0002026; P:regulation of the force of heart contraction; IMP:RGD.
DR   GO; GO:0055119; P:relaxation of cardiac muscle; ISO:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR   GO; GO:0007614; P:short-term memory; IMP:RGD.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0042098; P:T cell proliferation; ISO:RGD.
DR   GO; GO:0042311; P:vasodilation; IEP:RGD.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 3.30.450.40; -; 2.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
DR   InterPro; IPR003018; GAF.
DR   InterPro; IPR029016; GAF-like_dom_sf.
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   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   PANTHER; PTHR11347:SF20; PHOSPHODIESTERASE; 1.
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; GAF domain-like; 2.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   2: Evidence at transcript level;
KW   Allosteric enzyme; Alternative splicing; cGMP; cGMP-binding; Hydrolase;
KW   Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Repeat; Zinc.
FT   CHAIN           1..833
FT                   /note="cGMP-specific 3',5'-cyclic phosphodiesterase"
FT                   /id="PRO_0000198825"
FT   DOMAIN          122..272
FT                   /note="GAF 1"
FT   DOMAIN          304..461
FT                   /note="GAF 2"
FT   DOMAIN          494..818
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          82..101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        571
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O76083"
FT   BINDING         575
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   BINDING         611
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   BINDING         612
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   BINDING         612
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   BINDING         722
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   BINDING         775
FT                   /ligand="3',5'-cyclic GMP"
FT                   /ligand_id="ChEBI:CHEBI:57746"
FT                   /evidence="ECO:0000250|UniProtKB:O76074"
FT   MOD_RES         60
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   833 AA;  94556 MW;  712DC159C80CB09D CRC64;
     MLPFGDKTRD MVNAWFSERV HNIPVCKEGI RAHTESCSCS LPQSPHADNT TPGAPARKIS
     ASEFDRPLRP IVVKDSEGTV SFLSDSGKKE QMPLTSPRFD SDEGDQCSRL LELVKDISSH
     LDVTALCHKI FLHIHGLISA DRYSLFLVCE DSSKDKFLVS RLFDVAEGST LEEASNNCIR
     LEWNKGIVGH VAAFGEPLNI KDAYEDPRFN AEVDQITGYK TQSILCMPIK NHREEVVGVA
     QAINKKSGNG GTFTEKDEKD FAAYLAFCGI VLHNAQLYET SLLENKRNQV LLDLASLIFE
     EQQSLEVILK KIAATIISFM QVQKCTIFIV DEDCPDSFSR VFQMEWEEVG KSSEPLTREH
     DANKINYMYA QYVKNTMEPL NIPDVTKDNR FPWTNENMGH INTHCIRSLL CTPIKNGKKN
     KVIGVCQLVN KMEEKTGKIK AFNQNDEQFL EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT
     LEVLSYHASA AEEETRELQA LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL
     NLVQNFQMKH EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE
     TLALLIAALS HDLDHRGVNN SYIQRSEHPL AQLYCHSTME HHHFDQCLMV LNSPGNQILS
     GLSIEEYKTT LKIIKQAILA TDLALYIKRR GEFFELIRKN EFSFEDPLQK ELFLAMLMTA
     CDLSAITKPW PIQQRIAELV AAEFFDQGDR ERKELNMEPA DLMNREKKNK IPSMQVGFID
     AICLQLYEAL THVSEDCLPL LDGCRKNRQK WQALADQQEK TLLNGESGQA KRD
//