PDE2A_BOVIN
ID PDE2A_BOVIN Reviewed; 921 AA.
AC P14099; Q28064;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=cGMP-dependent 3',5'-cyclic phosphodiesterase {ECO:0000305|PubMed:1654333};
DE EC=3.1.4.17 {ECO:0000269|PubMed:1654333};
DE AltName: Full=Cyclic GMP-stimulated phosphodiesterase {ECO:0000303|PubMed:1654333};
DE Short=CGS-PDE {ECO:0000303|PubMed:1654333};
DE Short=cGSPDE {ECO:0000303|PubMed:1654333};
GN Name=PDE2A {ECO:0000250|UniProtKB:O00408};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=1654333; DOI=10.1016/s0021-9258(19)47421-8;
RA Sonnenburg W.K., Mullaney P.J., Beavo J.A.;
RT "Molecular cloning of a cyclic GMP-stimulated cyclic nucleotide
RT phosphodiesterase cDNA. Identification and distribution of isozyme
RT variants.";
RL J. Biol. Chem. 266:17655-17661(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A3).
RC TISSUE=Brain;
RA Juilfs D.M., Sonnenburg W.K., Seraji S., Beavo J.A.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 592-921, AND ACETYLATION AT MET-1.
RC TISSUE=Heart;
RX PubMed=2176866; DOI=10.1021/bi00496a018;
RA le Trong H., Beier N., Sonnenburg W.K., Stroop S.D., Walsh K.A.,
RA Beavo J.A., Charbonneau H.;
RT "Amino acid sequence of the cyclic GMP stimulated cyclic nucleotide
RT phosphodiesterase from bovine heart.";
RL Biochemistry 29:10280-10288(1990).
RN [4]
RP PROTEIN SEQUENCE OF 613-694 AND 808-868.
RC TISSUE=Heart;
RX PubMed=3025833; DOI=10.1073/pnas.83.24.9308;
RA Charbonneau H., Beier N., Walsh K.A., Beavo J.A.;
RT "Identification of a conserved domain among cyclic nucleotide
RT phosphodiesterases from diverse species.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9308-9312(1986).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=6276403; DOI=10.1016/s0021-9258(19)68134-2;
RA Martins T.J., Mumby M.C., Beavo J.A.;
RT "Purification and characterization of a cyclic GMP-stimulated cyclic
RT nucleotide phosphodiesterase from bovine tissues.";
RL J. Biol. Chem. 257:1973-1979(1982).
CC -!- FUNCTION: cGMP-activated cyclic nucleotide phosphodiesterase with a
CC dual-specificity for the second messengers cAMP and cGMP, which are key
CC regulators of many important physiological processes (PubMed:1654333,
CC PubMed:6276403). Has a higher efficiency with cGMP compared to cAMP (By
CC similarity). Plays a role in cell growth and migration (By similarity).
CC {ECO:0000250|UniProtKB:O00408, ECO:0000269|PubMed:1654333,
CC ECO:0000269|PubMed:6276403}.
CC -!- FUNCTION: [Isoform PDE2A2]: Regulates mitochondrial cAMP levels and
CC respiration. Involved in the regulation of mitochondria
CC morphology/dynamics and apoptotic cell death via local modulation of
CC cAMP/PKA signaling in the mitochondrion, including the monitoring of
CC local cAMP levels at the outer mitochondrial membrane and of PKA-
CC dependent phosphorylation of DNM1L. {ECO:0000250|UniProtKB:Q01062}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-
CC phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
CC Evidence={ECO:0000269|PubMed:1654333, ECO:0000269|PubMed:6276403};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:1654333};
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; Evidence={ECO:0000269|PubMed:1654333,
CC ECO:0000269|PubMed:6276403};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:1654333};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:1654333,
CC ECO:0000269|PubMed:6276403};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:1654333};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1654333};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000250|UniProtKB:O00408};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O00408};
CC Note=Binds 2 divalent metal cations per subunit. Site 2 has a
CC preference for magnesium ions. {ECO:0000250|UniProtKB:O00408};
CC -!- ACTIVITY REGULATION: The 3',5'-cyclic-AMP phosphodiesterase activity is
CC stimulated by 3',5'-cyclic GMP. {ECO:0000269|PubMed:1654333,
CC ECO:0000269|PubMed:6276403}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O00408}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A3]: Cell membrane
CC {ECO:0000250|UniProtKB:Q01062}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A1]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q01062}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A2]: Mitochondrion
CC {ECO:0000250|UniProtKB:Q01062}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q01062}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q01062}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=PDE2A1;
CC IsoId=P14099-1; Sequence=Displayed;
CC Name=PDE2A2;
CC IsoId=P14099-3; Sequence=Not described;
CC Name=PDE2A3;
CC IsoId=P14099-2; Sequence=VSP_004555;
CC -!- DOMAIN: The GAF 1 domain functions as a dimerization domain.
CC {ECO:0000250|UniProtKB:Q922S4}.
CC -!- DOMAIN: The GAF 2 domains binds cGMP, which acts as an allosteric
CC activator. {ECO:0000250|UniProtKB:Q922S4}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE2 subfamily. {ECO:0000305}.
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DR EMBL; M73512; AAA74559.1; -; mRNA.
DR EMBL; L49503; AAA87353.1; -; mRNA.
DR PIR; A40981; A40981.
DR RefSeq; NP_001137318.1; NM_001143846.1.
DR RefSeq; NP_001243202.1; NM_001256273.1. [P14099-1]
DR PDB; 3JAB; EM; 11.00 A; B/N=367-551.
DR PDB; 3JBQ; EM; 11.00 A; C/G=367-551.
DR PDBsum; 3JAB; -.
DR PDBsum; 3JBQ; -.
DR AlphaFoldDB; P14099; -.
DR SMR; P14099; -.
DR STRING; 9913.ENSBTAP00000011077; -.
DR BindingDB; P14099; -.
DR ChEMBL; CHEMBL3477; -.
DR DrugCentral; P14099; -.
DR iPTMnet; P14099; -.
DR PaxDb; P14099; -.
DR PRIDE; P14099; -.
DR GeneID; 281971; -.
DR KEGG; bta:281971; -.
DR CTD; 5138; -.
DR eggNOG; KOG3689; Eukaryota.
DR InParanoid; P14099; -.
DR OrthoDB; 904682at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0097060; C:synaptic membrane; IBA:GO_Central.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; ISS:UniProtKB.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; ISS:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISS:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISS:UniProtKB.
DR GO; GO:0046069; P:cGMP catabolic process; ISS:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0046038; P:GMP catabolic process; TAS:AgBase.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISS:UniProtKB.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IBA:GO_Central.
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; 1.
DR Pfam; PF13185; GAF_2; 1.
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; Acetylation; Alternative splicing; cAMP; Cell membrane; cGMP;
KW cGMP-binding; Cytoplasm; Direct protein sequencing; Hydrolase; Magnesium;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Nucleotide-binding; Reference proteome;
KW Repeat; Zinc.
FT CHAIN 1..921
FT /note="cGMP-dependent 3',5'-cyclic phosphodiesterase"
FT /id="PRO_0000198795"
FT DOMAIN 220..357
FT /note="GAF 1"
FT /evidence="ECO:0000255"
FT DOMAIN 389..528
FT /note="GAF 2"
FT /evidence="ECO:0000255"
FT DOMAIN 558..882
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 636
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 411
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 426
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 445
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 468
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 479
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 640
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 676
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 677
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 677
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 788
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:2176866"
FT VAR_SEQ 1..25
FT /note="MRRQPAASRDLFAQEPVPPGSGDGA -> MGQACGHSILCRSQQYPAARPAE
FT PRGQQVFLKPDEPPPPPQPCADS (in isoform PDE2A3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_004555"
FT CONFLICT 204
FT /note="N -> D (in Ref. 2; AAA87353)"
FT /evidence="ECO:0000305"
FT CONFLICT 633
FT /note="P -> L (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 921 AA; 103228 MW; E29F4C9875E83640 CRC64;
MRRQPAASRD LFAQEPVPPG SGDGALQDAL LSLGSVIDVA GLQQAVKEAL SAVLPKVETV
YTYLLDGESR LVCEEPPHEL PQEGKVREAV ISRKRLGCNG LGPSDLPGKP LARLVAPLAP
DTQVLVIPLV DKEAGAVAAV ILVHCGQLSD NEEWSLQAVE KHTLVALKRV QALQQRESSV
APEATQNPPE EAAGDQKGGV AYTNQDRKIL QLCGELYDLD ASSLQLKVLQ YLQQETQASR
CCLLLVSEDN LQLSCKVIGD KVLEEEISFP LTTGRLGQVV EDKKSIQLKD LTSEDMQQLQ
SMLGCEVQAM LCVPVISRAT DQVVALACAF NKLGGDLFTD QDEHVIQHCF HYTSTVLTST
LAFQKEQKLK CECQALLQVA KNLFTHLDDV SVLLQEIITE ARNLSNAEIC SVFLLDQNEL
VAKVFDGGVV EDESYEIRIP ADQGIAGHVA TTGQILNIPD AYAHPLFYRG VDDSTGFRTR
NILCFPIKNE NQEVIGVAEL VNKINGPWFS KFDEDLATAF SIYCGISIAH SLLYKKVNEA
QYRSHLANEM MMYHMKVSDD EYTKLLHDGI QPVAAIDSNF ASFTYTPRSL PEDDTSMAIL
SMLQDMNFIN NYKIDCPTLA RFCLMVKKGY RDPPYHNWMH AFSVSHFCYL LYKNLELTNY
LEDMEIFALF ISCMCHDLDH RGTNNSFQVA SKSVLAALYS SEGSVMERHH FAQAIAILNT
HGCNIFDHFS RKDYQRMLDL MRDIILATDL AHHLRIFKDL QKMAEVGYDR TNKQHHSLLL
CLLMTSCDLS DQTKGWKTTR KIAELIYKEF FSQGDLEKAM GNRPMEMMDR EKAYIPELQI
SFMEHIAMPI YKLLQDLFPK AAELYERVAS NREHWTKVSH KFTIRGLPSN NSLDFLDEEY
EVPDLDGARA PINGCCSLDA E
