PDE5A_RAT
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 03-AUG-2022, entry version 144.
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; O54735; -.
DR GeneID; 171115; -.
DR KEGG; rno:171115; -.
DR UCSC; RGD:620995; rat. [O54735-1]
DR CTD; 8654; -.
DR RGD; 620995; Pde5a.
DR eggNOG; KOG3689; Eukaryota.
DR InParanoid; O54735; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; O54735; -.
DR BRENDA; 3.1.4.35; 5301.
DR Reactome; R-RNO-418457; cGMP effects.
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:0005829; C:cytosol; IDA:RGD.
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: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:0043406; P:positive regulation of MAP kinase activity; ISO: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:0042311; P:vasodilation; IEP:RGD.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR Gene3D; 3.30.450.40; -; 2.
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 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 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
