PDE2A_MOUSE
ID PDE2A_MOUSE Reviewed; 939 AA.
AC Q922S4; Q3TCR8; Q3TXZ6; Q8K2U1;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=cGMP-dependent 3',5'-cyclic phosphodiesterase {ECO:0000305|PubMed:21724846};
DE EC=3.1.4.17 {ECO:0000269|PubMed:21724846};
DE AltName: Full=Cyclic GMP-stimulated phosphodiesterase;
DE Short=CGS-PDE;
DE Short=cGSPDE;
GN Name=Pde2a {ECO:0000312|MGI:MGI:2446107};
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] {ECO:0000312|EMBL:BAE34768.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS PDE2A2 AND PDE2A3).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE34768.1};
RC TISSUE=Visual cortex {ECO:0000312|EMBL:BAE34768.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE2A1).
RC TISSUE=Mammary tumor;
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 PROTEIN SEQUENCE OF 828-837, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP FUNCTION, FUNCTION (ISOFORM PDE2A2), CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION (ISOFORM PDE2A2), AND TISSUE SPECIFICITY (ISOFORM PDE2A2).
RX PubMed=21724846; DOI=10.1074/jbc.m111.266379;
RA Acin-Perez R., Russwurm M., Gunnewig K., Gertz M., Zoidl G., Ramos L.,
RA Buck J., Levin L.R., Rassow J., Manfredi G., Steegborn C.;
RT "A phosphodiesterase 2A isoform localized to mitochondria regulates
RT respiration.";
RL J. Biol. Chem. 286:30423-30432(2011).
RN [6]
RP FUNCTION (ISOFORM PDE2A2), DISRUPTION PHENOTYPE, AND ACTIVITY REGULATION.
RC TISSUE=Embryonic fibroblast;
RX PubMed=28463107; DOI=10.7554/elife.21374;
RA Monterisi S., Lobo M.J., Livie C., Castle J.C., Weinberger M., Baillie G.,
RA Surdo N.C., Musheshe N., Stangherlin A., Gottlieb E., Maizels R.,
RA Bortolozzi M., Micaroni M., Zaccolo M.;
RT "PDE2A2 regulates mitochondria morphology and apoptotic cell death via
RT local modulation of cAMP/PKA signalling.";
RL Elife 6:0-0(2017).
RN [7] {ECO:0007744|PDB:1MC0}
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 217-561 IN COMPLEX WITH CGMP,
RP DOMAIN, AND SUBUNIT.
RX PubMed=12271124; DOI=10.1073/pnas.192374899;
RA Martinez S.E., Wu A.Y., Glavas N.A., Tang X.-B., Turley S., Hol W.G.J.,
RA Beavo J.A.;
RT "The two GAF domains in phosphodiesterase 2A have distinct roles in
RT dimerization and in cGMP binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13260-13265(2002).
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:21724846).
CC Has a higher efficiency with cGMP compared to cAMP (By similarity).
CC Plays a role in cell growth and migration (By similarity).
CC {ECO:0000250|UniProtKB:O00408, ECO:0000269|PubMed:21724846}.
CC -!- FUNCTION: [Isoform PDE2A2]: Regulates mitochondrial cAMP levels and
CC respiration (PubMed:21724846). Involved in the regulation of
CC mitochondria morphology/dynamics and apoptotic cell death via local
CC modulation of cAMP/PKA signaling in the mitochondrion, including the
CC monitoring of local cAMP levels at the outer mitochondrial membrane and
CC of PKA-dependent phosphorylation of DNM1L (PubMed:28463107).
CC {ECO:0000269|PubMed:21724846, ECO:0000269|PubMed:28463107}.
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:21724846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:21724846};
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:21724846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:21724846};
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:21724846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:21724846};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O00408};
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 (By similarity). Specifically inhibited
CC by Bay 60-7550 (PubMed:28463107). {ECO:0000250|UniProtKB:O00408,
CC ECO:0000269|PubMed:28463107}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12271124}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A1]: Cytoplasm
CC {ECO:0000250|UniProtKB:O00408}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A2]: Mitochondrion matrix
CC {ECO:0000269|PubMed:21724846}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:O00408}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:O00408}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A3]: Cell membrane
CC {ECO:0000250|UniProtKB:O00408}; Lipid-anchor
CC {ECO:0000250|UniProtKB:O00408}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=PDE2A3 {ECO:0000305};
CC IsoId=Q922S4-1; Sequence=Displayed;
CC Name=PDE2A1 {ECO:0000305};
CC IsoId=Q922S4-2; Sequence=VSP_059396, VSP_059397;
CC Name=PDE2A2 {ECO:0000303|PubMed:21724846};
CC IsoId=Q922S4-3; Sequence=VSP_059395, VSP_059397;
CC -!- TISSUE SPECIFICITY: [Isoform PDE2A2]: Expressed in brain and liver (at
CC protein level). {ECO:0000269|PubMed:21724846}.
CC -!- DOMAIN: The GAF 1 domain functions as a dimerization domain.
CC {ECO:0000269|PubMed:12271124}.
CC -!- DOMAIN: The GAF 2 domains binds cGMP, which acts as an allosteric
CC activator. {ECO:0000269|PubMed:12271124}.
CC -!- DISRUPTION PHENOTYPE: Abnormally elongated mitochondria. This phenotype
CC is reversed by treatment with the PKA inhibitor H89. Protected from
CC ionomycin- but not staurosporin-induced cell death.
CC {ECO:0000269|PubMed:28463107}.
CC -!- MISCELLANEOUS: [Isoform PDE2A2]: Contains a transit peptide at
CC positions 1-17. {ECO:0000269|PubMed:21724846}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE2 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC057029; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK159012; BAE34768.1; -; mRNA.
DR EMBL; AK170573; BAE41887.1; -; mRNA.
DR EMBL; AC129079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC129609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006845; AAH06845.1; -; mRNA.
DR EMBL; BC029810; AAH29810.1; -; mRNA.
DR EMBL; BC057029; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS52330.1; -. [Q922S4-1]
DR RefSeq; NP_001137320.1; NM_001143848.2. [Q922S4-1]
DR RefSeq; NP_001137321.1; NM_001143849.2. [Q922S4-3]
DR RefSeq; XP_006507590.1; XM_006507527.3.
DR PDB; 1MC0; X-ray; 2.86 A; A=217-561.
DR PDBsum; 1MC0; -.
DR AlphaFoldDB; Q922S4; -.
DR SMR; Q922S4; -.
DR IntAct; Q922S4; 4.
DR MINT; Q922S4; -.
DR STRING; 10090.ENSMUSP00000131553; -.
DR PhosphoSitePlus; Q922S4; -.
DR SwissPalm; Q922S4; -.
DR MaxQB; Q922S4; -.
DR PaxDb; Q922S4; -.
DR PeptideAtlas; Q922S4; -.
DR PRIDE; Q922S4; -.
DR ProteomicsDB; 294040; -. [Q922S4-1]
DR ProteomicsDB; 340613; -.
DR DNASU; 207728; -.
DR Ensembl; ENSMUST00000163751; ENSMUSP00000131553; ENSMUSG00000110195. [Q922S4-1]
DR GeneID; 207728; -.
DR KEGG; mmu:207728; -.
DR UCSC; uc009ioq.3; mouse. [Q922S4-1]
DR UCSC; uc012fqk.2; mouse.
DR CTD; 5138; -.
DR MGI; MGI:2446107; Pde2a.
DR VEuPathDB; HostDB:ENSMUSG00000110195; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000159817; -.
DR InParanoid; Q922S4; -.
DR OrthoDB; 904682at2759; -.
DR TreeFam; TF316499; -.
DR BRENDA; 3.1.4.17; 3474.
DR Reactome; R-MMU-418457; cGMP effects.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 207728; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Pde2a; mouse.
DR EvolutionaryTrace; Q922S4; -.
DR PRO; PR:Q922S4; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q922S4; protein.
DR Bgee; ENSMUSG00000110195; Expressed in striatum and 92 other tissues.
DR ExpressionAtlas; Q922S4; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0097457; C:hippocampal mossy fiber; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IMP:UniProtKB.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IMP:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IMP:UniProtKB.
DR GO; GO:0030553; F:cGMP binding; IDA:UniProtKB.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0036004; F:GAF domain binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0042301; F:phosphate ion binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030911; F:TPR domain binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0003279; P:cardiac septum development; IMP:MGI.
DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; ISO:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI.
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:0071222; P:cellular response to lipopolysaccharide; IEP: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; IDA:UniProtKB.
DR GO; GO:0046069; P:cGMP catabolic process; IMP:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0003170; P:heart valve development; IMP:MGI.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:UniProtKB.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0090324; P:negative regulation of oxidative phosphorylation; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP: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:0010752; P:regulation of cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; IGI:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0003281; P:ventricular septum development; 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; 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; Alternative splicing; cAMP; Cell membrane; cGMP;
KW cGMP-binding; Cytoplasm; Direct protein sequencing; Hydrolase; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Mitochondrion outer membrane; Myristate;
KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT CHAIN 2..939
FT /note="cGMP-dependent 3',5'-cyclic phosphodiesterase"
FT /id="PRO_0000198797"
FT DOMAIN 236..373
FT /note="GAF 1"
FT /evidence="ECO:0000255"
FT DOMAIN 408..547
FT /note="GAF 2"
FT /evidence="ECO:0000255"
FT DOMAIN 577..901
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 16..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 655
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 430
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12271124,
FT ECO:0007744|PDB:1MC0"
FT BINDING 445
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12271124,
FT ECO:0007744|PDB:1MC0"
FT BINDING 464
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12271124,
FT ECO:0007744|PDB:1MC0"
FT BINDING 487
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12271124,
FT ECO:0007744|PDB:1MC0"
FT BINDING 498
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12271124,
FT ECO:0007744|PDB:1MC0"
FT BINDING 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 695
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 696
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 696
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT BINDING 807
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01062"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O00408"
FT VAR_SEQ 1..46
FT /note="MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPQPCADSLQ -> MR
FT RQPAASQDPLAQKPEPPGSRDDRLE (in isoform PDE2A1)"
FT /evidence="ECO:0000305"
FT /id="VSP_059396"
FT VAR_SEQ 1..24
FT /note="MGQACGHSILCRSQQYPAARPAEP -> MVLVLHHILIAVVQFLR (in
FT isoform PDE2A2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059395"
FT VAR_SEQ 353..356
FT /note="Missing (in isoform PDE2A1 and isoform PDE2A2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059397"
FT CONFLICT 596
FT /note="D -> G (in Ref. 1; BAE41887)"
FT /evidence="ECO:0000305"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 236..250
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 253..261
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 267..273
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 276..290
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 308..318
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:1MC0"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 337..349
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 360..404
FT /evidence="ECO:0007829|PDB:1MC0"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:1MC0"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 412..424
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 426..434
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 436..444
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 463..471
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 475..478
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 491..494
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 501..507
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 513..522
FT /evidence="ECO:0007829|PDB:1MC0"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:1MC0"
FT HELIX 530..558
FT /evidence="ECO:0007829|PDB:1MC0"
SQ SEQUENCE 939 AA; 105619 MW; 1DD7BD9DBCF806E3 CRC64;
MGQACGHSIL CRSQQYPAAR PAEPRGQQVF LKPDEPPPQP CADSLQDALL SLGAVIDIAG
LRQAARDALS AVLPKVETVY TYLLDGESRL VCEDPPHELP QEGKIREAVI SQKRLSCNGL
GPSDLLGKPL ARLVAPLAPD MQVLVIPLLD KETGSVAAVI LVHCGQLSDS EEQSLQVVEK
HALVALRRVQ ALQQRRPEAV QNTSVDASED QKDEKGYTDH DRKILQLCGE LFDLDATSLQ
LKVLQYLQQE TQATHCCLLL VSEDNLQLSC KVIGDKVLGE EVSFPLTMGR LGQVVEDKQC
IQLKDLTSDD VQQLQNMLGC ELQAMLCVPV ISRATDQVVA LACAFNKLGG DFPTSSFTDE
DEHVIQHCFH YTGTVLTSTL AFQKEQKLKC ECQALLQVAK NLFTHLDDVS VLLQEIITEA
RNLSNAEICS VFLLDQNELV AKVFDGGVVD DESYEIRIPA DQGIAGHVAT TGQILNIPDA
YAHPLFYRGV DDSTGFRTRN ILCFPIKNEN QEVIGVAELV NKINGPWFSK FDEDLATAFS
IYCGISIAHS LLYKKVNEAQ YRSHLANEMM MYHMKVSDDE YTKLLHDGIQ PVAAIDSNFA
NFTYTPRSLP EDDTSMAILS MLQDMNFINN YKIDCPTLAR FCLMVKKGYR DPPYHNWMHA
FSVSHFCYLL YKNLELSNYL EDIEIFALFI SCMCHDLDHR GTNNSFQVAS KSVLAALYSS
EGSVMERHHF AQAIAILNTH GCNIFDHFSR KDYQRMLDLM RDIILATDLA HHLRIFKDLQ
KMAEVGYDRN NRQHHRLLLC LLMTSCDLSD QTKGWKTTRK IAELIYKEFF SQGDLEKAMG
NRPMEMMDRE KAYIPELQIS FMEHIAMPIY KLLQDLFPKA AELYERVASN REHWTKVSHK
FTIRGLPSNN SLDFLDEEYE VPDLDGTRAP VNGCCSLEG
