PDE5A_CANLF
ID PDE5A_CANLF Reviewed; 865 AA.
AC O77746; O77747;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 145.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE5A1 AND PDE5A2).
RC TISSUE=Lung;
RX PubMed=9756948; DOI=10.1074/jbc.273.41.26982;
RA Kotera J., Fujishige K., Akatsuka H., Imai Y., Yanaka N., Omori K.;
RT "Novel alternative splice variants of cGMP-binding cGMP-specific
RT phosphodiesterase.";
RL J. Biol. Chem. 273:26982-26990(1998).
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 -!- ACTIVITY REGULATION: Inhibited by zaprinast.
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC 3',5'-cyclic GMP: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol. Note=PDE5A1 and
CC PDE5A2 are located mostly to soluble cellular fractions and some to
CC particulate cellular fractions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=PDE5A1;
CC IsoId=O77746-1; Sequence=Displayed;
CC Name=PDE5A2;
CC IsoId=O77746-2; Sequence=VSP_004590;
CC -!- TISSUE SPECIFICITY: Isoform PDE5A1 and isoform PDE5A2 are highly
CC expressed in the cerebellum, hippocampus, retina, lung, heart, spleen,
CC and thoracic artery. Isoform PDE5A1, but not isoform PDE5A2, is also
CC abundantly expressed in the pylorus.
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 -!- MISCELLANEOUS: cGMP-binding to the allosteric sites is stimulated by 3-
CC isobutyl-1-methylxanthine (IBMX).
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {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; AB008467; BAA33503.1; -; mRNA.
DR EMBL; AB008468; BAA33504.1; -; mRNA.
DR RefSeq; NP_001003188.1; NM_001003188.1. [O77746-2]
DR RefSeq; XP_005639100.1; XM_005639043.2. [O77746-1]
DR AlphaFoldDB; O77746; -.
DR SMR; O77746; -.
DR STRING; 9612.ENSCAFP00000034752; -.
DR BindingDB; O77746; -.
DR ChEMBL; CHEMBL2304402; -.
DR DrugCentral; O77746; -.
DR PaxDb; O77746; -.
DR Ensembl; ENSCAFT00040036119; ENSCAFP00040031453; ENSCAFG00040019329. [O77746-2]
DR GeneID; 403825; -.
DR KEGG; cfa:403825; -.
DR CTD; 8654; -.
DR eggNOG; KOG3689; Eukaryota.
DR HOGENOM; CLU_006980_0_2_1; -.
DR InParanoid; O77746; -.
DR OMA; RDAYKHE; -.
DR OrthoDB; 904682at2759; -.
DR TreeFam; TF316499; -.
DR Reactome; R-CFA-418457; cGMP effects.
DR Reactome; R-CFA-9013422; RHOBTB1 GTPase cycle.
DR UniPathway; UPA00763; UER00748.
DR Proteomes; UP000002254; Unplaced.
DR Bgee; ENSCAFG00000012472; Expressed in jejunum and 45 other tissues.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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; Cytoplasm;
KW Hydrolase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Zinc.
FT CHAIN 1..865
FT /note="cGMP-specific 3',5'-cyclic phosphodiesterase"
FT /id="PRO_0000198822"
FT DOMAIN 154..304
FT /note="GAF 1"
FT DOMAIN 336..493
FT /note="GAF 2"
FT DOMAIN 526..850
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 69..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..89
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 603
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 607
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT BINDING 643
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT BINDING 644
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT BINDING 644
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT BINDING 754
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT BINDING 807
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76074"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..40
FT /note="MERGSPGAGAARLPRDQDSVEAWLDDHRDFTFSYFVKKAT -> MLPFGHQR
FT (in isoform PDE5A2)"
FT /evidence="ECO:0000303|PubMed:9756948"
FT /id="VSP_004590"
SQ SEQUENCE 865 AA; 98294 MW; F20BB37B71E93BB6 CRC64;
MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE RVHTIPVCKE
GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL RPIVVKDSEG TVSFLADSEK
KEQMPLTPPR FDNDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV
CEDSSNDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAALGEPL NIKDAYEDPR
FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC
GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS FMQVQKCTIF
IVDEDCSDSF SSVFHMECEE LEKLPDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD
KRFPWTNENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ
FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETKEL 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 PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR
QKWQALAEQQ EKTLINGESS QAKRN
