PDE5A_MOUSE
ID PDE5A_MOUSE Reviewed; 865 AA.
AC Q8CG03; Q0VBW0;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 141.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Burns F., Sonnenburg W.K., Rybalkin S.D., Beavo J.A.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 -!- 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; AF541937; AAN17330.1; -; mRNA.
DR EMBL; CH466532; EDL12317.1; -; Genomic_DNA.
DR EMBL; BC119137; AAI19138.1; -; mRNA.
DR EMBL; BC120486; AAI20487.1; -; mRNA.
DR CCDS; CCDS17812.1; -.
DR RefSeq; NP_700471.2; NM_153422.2.
DR PDB; 2K31; NMR; -; A=154-320.
DR PDBsum; 2K31; -.
DR AlphaFoldDB; Q8CG03; -.
DR SMR; Q8CG03; -.
DR BioGRID; 232382; 5.
DR IntAct; Q8CG03; 1.
DR STRING; 10090.ENSMUSP00000069011; -.
DR iPTMnet; Q8CG03; -.
DR PhosphoSitePlus; Q8CG03; -.
DR jPOST; Q8CG03; -.
DR MaxQB; Q8CG03; -.
DR PaxDb; Q8CG03; -.
DR PeptideAtlas; Q8CG03; -.
DR PRIDE; Q8CG03; -.
DR ProteomicsDB; 301780; -.
DR Antibodypedia; 1386; 184 antibodies from 36 providers.
DR DNASU; 242202; -.
DR Ensembl; ENSMUST00000066728; ENSMUSP00000069011; ENSMUSG00000053965.
DR GeneID; 242202; -.
DR KEGG; mmu:242202; -.
DR UCSC; uc008ret.2; mouse.
DR CTD; 8654; -.
DR MGI; MGI:2651499; Pde5a.
DR VEuPathDB; HostDB:ENSMUSG00000053965; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000155475; -.
DR InParanoid; Q8CG03; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q8CG03; -.
DR TreeFam; TF316499; -.
DR BRENDA; 3.1.4.35; 3474.
DR Reactome; R-MMU-418457; cGMP effects.
DR Reactome; R-MMU-9013422; RHOBTB1 GTPase cycle.
DR UniPathway; UPA00763; UER00748.
DR BioGRID-ORCS; 242202; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Pde5a; mouse.
DR EvolutionaryTrace; Q8CG03; -.
DR PRO; PR:Q8CG03; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8CG03; protein.
DR Bgee; ENSMUSG00000053965; Expressed in left lung lobe and 202 other tissues.
DR ExpressionAtlas; Q8CG03; baseline and differential.
DR Genevisible; Q8CG03; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; ISO:MGI.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IMP:MGI.
DR GO; GO:0030553; F:cGMP binding; IDA:MGI.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IDA:MGI.
DR GO; GO:0046068; P:cGMP metabolic process; IMP:MGI.
DR GO; GO:0055118; P:negative regulation of cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0048599; P:oocyte development; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
DR GO; GO:0002678; P:positive regulation of chronic inflammatory response; ISO:MGI.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IC:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0060282; P:positive regulation of oocyte development; IMP:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; IGI:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:MGI.
DR GO; GO:0055119; P:relaxation of cardiac muscle; IMP:BHF-UCL.
DR GO; GO:0007614; P:short-term memory; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
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 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; cGMP; cGMP-binding; Hydrolase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Zinc.
FT CHAIN 1..865
FT /note="cGMP-specific 3',5'-cyclic phosphodiesterase"
FT /id="PRO_0000198824"
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 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 CONFLICT 176
FT /note="S -> T (in Ref. 1; AAN17330)"
FT /evidence="ECO:0000305"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:2K31"
FT TURN 167..171
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 173..183
FT /evidence="ECO:0007829|PDB:2K31"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 187..197
FT /evidence="ECO:0007829|PDB:2K31"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2K31"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2K31"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:2K31"
FT HELIX 245..249
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:2K31"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:2K31"
FT STRAND 267..275
FT /evidence="ECO:0007829|PDB:2K31"
FT HELIX 287..300
FT /evidence="ECO:0007829|PDB:2K31"
SQ SEQUENCE 865 AA; 98407 MW; BADD21CC6B62045E CRC64;
MERAGPNSVR SQQQRDPDWV EAWLDDHRDF TFSYFIRKAT RDMVNAWFSE RVHNIPVCKE
GIRAHTESCS CSLQQSPHAD NTTPGAPARK ISASEFDRPL RPIVVKDSEG TVSFLSDSGK
KEQMPLTPPR FDSDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV
CEDSSKDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAAFGEPL NIKDAYEDPR
FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC
GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS FMQVQKCTIF
IVDEDCPDSF SRVFHMECEE VGKPSDPLTR EQDANKINYM YAQYVKNTME PLNIPDVTKD
KRFPWTNENM GHVNTPCIGS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK IKAFNQNDEQ
FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL QALSAAVVPS
AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV
AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LETLALLIAA LSHDLDHRGV NNSYIQRSEH
PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIDEYK TTLKIIKQAI LATDLALYIK
RRGEFFELIR KNQFSFEDPL QKELFLAMLM TACDLSAITK PWPIQQRIAE LVAAEFFDQG
DRERKELNME PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCL PLLDGCRKNR
QKWQALAEQQ EKMLLNGESS QGKRD
