PDE2A_HUMAN
ID PDE2A_HUMAN Reviewed; 941 AA.
AC O00408; B2R646; B3KRV5; E9PGI1; F6W5Z0; Q5J791; Q5J792; Q5J793; Q6ZMR1;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=cGMP-dependent 3',5'-cyclic phosphodiesterase {ECO:0000305|PubMed:9210593};
DE EC=3.1.4.17 {ECO:0000269|PubMed:15938621, ECO:0000269|PubMed:29392776, ECO:0000269|PubMed:9210593};
DE AltName: Full=Cyclic GMP-stimulated phosphodiesterase;
DE Short=CGS-PDE;
DE Short=cGSPDE;
GN Name=PDE2A {ECO:0000312|HGNC:HGNC:8777};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A3), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain, and Hippocampus;
RX PubMed=9210593; DOI=10.1016/s0378-1119(97)00046-2;
RA Rosman G.J., Martins T.J., Sonnenburg W.K., Beavo J.A., Ferguson K.,
RA Loughney K.;
RT "Isolation and characterization of human cDNAs encoding a cGMP-stimulated
RT 3',5'-cyclic nucleotide phosphodiesterase.";
RL Gene 191:89-95(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A4), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1-27 (ISOFORM PDE2A1), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1-55 (ISOFORM
RP PDE2A2).
RA Bugaj-Gaweda B., De Vivo M., Wang D.;
RT "Human PDE2A1, PDE2A2 and PDE2A4.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS PDE2A3; 5 AND 6).
RC TISSUE=Adrenal gland, Brain, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP MYRISTOYLATION AT GLY-2, PALMITOYLATION AT CYS-5 AND CYS-11, AND
RP SUBCELLULAR LOCATION (ISOFORMS PDE2A1 AND PDE2A3).
RX PubMed=19632989; DOI=10.1074/jbc.m109.017194;
RA Russwurm C., Zoidl G., Koesling D., Russwurm M.;
RT "Dual acylation of PDE2A splice variant 3: targeting to synaptic
RT membranes.";
RL J. Biol. Chem. 284:25782-25790(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [7]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [8]
RP FUNCTION.
RX PubMed=24705027; DOI=10.1016/j.cellsig.2014.03.031;
RA Hiramoto K., Murata T., Shimizu K., Morita H., Inui M., Manganiello V.C.,
RA Tagawa T., Arai N.;
RT "Role of phosphodiesterase 2 in growth and invasion of human malignant
RT melanoma cells.";
RL Cell. Signal. 26:1807-1817(2014).
RN [9]
RP FUNCTION (ISOFORM PDE2A2), AND SUBCELLULAR LOCATION (ISOFORMS PDE2A1;
RP PDE2A2 AND PDE2A3).
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 [10]
RP INVOLVEMENT IN IDDPADS, VARIANT IDDPADS GLY-480, CHARACTERIZATION OF
RP VARIANT IDDPADS GLY-480, FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=29392776; DOI=10.1002/mds.27286;
RA Salpietro V., Perez-Duenas B., Nakashima K., San Antonio-Arce V.,
RA Manole A., Efthymiou S., Vandrovcova J., Bettencourt C., Mencacci N.E.,
RA Klein C., Kelly M.P., Davies C.H., Kimura H., Macaya A., Houlden H.;
RT "A homozygous loss-of-function mutation in PDE2A associated to early-onset
RT hereditary chorea.";
RL Mov. Disord. 33:482-488(2018).
RN [11]
RP INVOLVEMENT IN IDDPADS, AND VARIANTS IDDPADS LEU-149 AND 394-GLN--GLU-941
RP DEL.
RX PubMed=32467598; DOI=10.1038/s41431-020-0641-9;
RA Doummar D., Dentel C., Lyautey R., Metreau J., Keren B., Drouot N.,
RA Malherbe L., Bouilleret V., Courraud J., Valenti-Hirsch M.P., Minotti L.,
RA Dozieres-Puyravel B., Baer S., Scholly J., Schaefer E., Nava C., Wirth T.,
RA Nasser H., de Salins M., de Saint Martin A., Warde M.T.A., Kahane P.,
RA Hirsch E., Anheim M., Friant S., Chelly J., Mignot C., Rudolf G.;
RT "Biallelic PDE2A variants: a new cause of syndromic paroxysmal
RT dyskinesia.";
RL Eur. J. Hum. Genet. 28:1403-1413(2020).
RN [12]
RP INVOLVEMENT IN IDDPADS.
RX PubMed=32196122; DOI=10.1002/mds.28023;
RA Haidar Z., Jalkh N., Corbani S., Abou-Ghoch J., Fawaz A., Mehawej C.,
RA Chouery E.;
RT "A homozygous splicing mutation in PDE2A in a family with atypical Rett
RT syndrome.";
RL Mov. Disord. 35:896-899(2020).
RN [13] {ECO:0007744|PDB:1Z1L}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 578-919 IN COMPLEX WITH ZINC;
RP MAGNESIUM AND PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF ASP-811;
RP GLN-812; THR-819; ILE-826; TYR-827; MET-847; LEU-858 AND LEU-907.
RX PubMed=15938621; DOI=10.1021/bi047313h;
RA Iffland A., Kohls D., Low S., Luan J., Zhang Y., Kothe M., Cao Q.,
RA Kamath A.V., Ding Y.H., Ellenberger T.;
RT "Structural determinants for inhibitor specificity and selectivity in PDE2A
RT using the wheat germ in vitro translation system.";
RL Biochemistry 44:8312-8325(2005).
RN [14] {ECO:0007744|PDB:3IBJ, ECO:0007744|PDB:3ITM, ECO:0007744|PDB:3ITU}
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 215-919 IN COMPLEX WITH ZINC;
RP MAGNESIUM AND THE INHIBITOR IBMX, FUNCTION, COFACTOR, AND SUBUNIT.
RX PubMed=19828435; DOI=10.1073/pnas.0907635106;
RA Pandit J., Forman M.D., Fennell K.F., Dillman K.S., Menniti F.S.;
RT "Mechanism for the allosteric regulation of phosphodiesterase 2A deduced
RT from the X-ray structure of a near full-length construct.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18225-18230(2009).
RN [15] {ECO:0007744|PDB:4HTX, ECO:0007744|PDB:4HTZ}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 578-919 IN COMPLEX WITH ZINC;
RP MAGNESIUM AND INHIBITOR, COFACTOR, AND SUBUNIT.
RX PubMed=23899287; DOI=10.1021/ja404449g;
RA Zhu J., Yang Q., Dai D., Huang Q.;
RT "X-ray crystal structure of phosphodiesterase 2 in complex with a highly
RT selective, nanomolar inhibitor reveals a binding-induced pocket important
RT for selectivity.";
RL J. Am. Chem. Soc. 135:11708-11711(2013).
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:9210593,
CC PubMed:29392776, PubMed:15938621). Has a higher efficiency with cGMP
CC compared to cAMP (PubMed:15938621). Plays a role in cell growth and
CC migration (PubMed:24705027). {ECO:0000269|PubMed:15938621,
CC ECO:0000269|PubMed:24705027, ECO:0000269|PubMed:29392776,
CC ECO:0000269|PubMed:9210593}.
CC -!- FUNCTION: [Isoform PDE2A2]: Regulates mitochondrial cAMP levels and
CC respiration (By similarity). 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 (PubMed:28463107).
CC {ECO:0000250|UniProtKB:Q922S4, 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:15938621, ECO:0000269|PubMed:29392776,
CC ECO:0000269|PubMed:9210593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:9210593};
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:15938621,
CC ECO:0000269|PubMed:29392776, ECO:0000269|PubMed:9210593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:9210593};
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:15938621,
CC ECO:0000269|PubMed:29392776, ECO:0000269|PubMed:9210593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:9210593};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15938621, ECO:0000269|PubMed:19828435,
CC ECO:0000269|PubMed:23899287};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000269|PubMed:15938621,
CC ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15938621, ECO:0000269|PubMed:19828435,
CC ECO:0000269|PubMed:23899287};
CC Note=Binds 2 divalent metal cations per subunit. Site 2 has a
CC preference for magnesium ions. {ECO:0000269|PubMed:15938621,
CC ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287};
CC -!- ACTIVITY REGULATION: The 3',5'-cyclic-AMP phosphodiesterase activity is
CC stimulated by 3',5'-cyclic GMP. {ECO:0000269|PubMed:9210593}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=43.7 uM for 3',5'-cyclic GMP {ECO:0000269|PubMed:15938621};
CC KM=32 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:15938621};
CC Vmax=20.5 nmol/min/mg enzyme for 3',5'-cyclic AMP
CC {ECO:0000269|PubMed:9210593};
CC Vmax=28.5 nmol/min/mg enzyme for 3',5'-cyclic GMP
CC {ECO:0000269|PubMed:9210593};
CC Note=kcat is 0.6 sec(-1) with 3',5'-cyclic GMP as substrate
CC (PubMed:15938621). kcat is 0.12 sec(-1) with 3',5'-cyclic AMP as
CC substrate (PubMed:15938621). {ECO:0000269|PubMed:15938621};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15938621,
CC ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287}.
CC -!- INTERACTION:
CC O00408; O00170: AIP; NbExp=6; IntAct=EBI-1785967, EBI-704197;
CC O00408-1; O00408-1: PDE2A; NbExp=3; IntAct=EBI-15809759, EBI-15809759;
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A3]: Cell membrane
CC {ECO:0000269|PubMed:19632989, ECO:0000269|PubMed:28463107}; Lipid-
CC anchor {ECO:0000269|PubMed:19632989}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A2]: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q922S4}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:28463107}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:28463107}.
CC -!- SUBCELLULAR LOCATION: [Isoform PDE2A1]: Cytoplasm
CC {ECO:0000269|PubMed:19632989, ECO:0000269|PubMed:28463107}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Mitochondrion {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist. Experimental confirmation
CC may be lacking for some isoforms.;
CC Name=PDE2A3;
CC IsoId=O00408-1; Sequence=Displayed;
CC Name=PDE2A1;
CC IsoId=O00408-2; Sequence=VSP_055315;
CC Name=PDE2A2;
CC IsoId=O00408-3; Sequence=VSP_055316;
CC Name=PDE2A4;
CC IsoId=O00408-4; Sequence=VSP_055317;
CC Name=5;
CC IsoId=O00408-5; Sequence=VSP_055316, VSP_055318;
CC Name=6;
CC IsoId=O00408-6; Sequence=VSP_055315, VSP_055319, VSP_055320;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9210593, PubMed:29392776).
CC Expressed in brain, with high expression observed in the corpus
CC striatum (PubMed:29392776). Also expressed in heart, placenta, lung,
CC skeletal muscle, kidney and pancreas (PubMed:9210593, PubMed:29392776).
CC {ECO:0000269|PubMed:29392776, ECO:0000269|PubMed:9210593}.
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 -!- DISEASE: Intellectual developmental disorder with paroxysmal dyskinesia
CC or seizures (IDDPADS) [MIM:619150]: An autosomal recessive disorder
CC characterized by global developmental delay, impaired intellectual
CC development, language delay, and early-onset paroxysmal hyperkinetic
CC movement disorder that manifests as sudden falls or backward
CC propulsion, eye or head deviation, and dystonic limb posturing followed
CC by chorea and dyskinetic movements. Some patients may also develop
CC epileptic seizures or only have seizures without a movement disorder.
CC {ECO:0000269|PubMed:29392776, ECO:0000269|PubMed:32196122,
CC ECO:0000269|PubMed:32467598}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform PDE2A1]: Soluble form. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform PDE2A2]: Contains a transit peptide at
CC positions 1-17. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE2 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAS75515.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U67733; AAC51320.1; -; mRNA.
DR EMBL; AY495087; AAS75513.1; -; mRNA.
DR EMBL; AY495088; AAS75514.1; -; mRNA.
DR EMBL; AY495089; AAS75515.1; ALT_FRAME; mRNA.
DR EMBL; AK092278; BAG52517.1; -; mRNA.
DR EMBL; AK131525; BAD18664.1; -; mRNA.
DR EMBL; AK312434; BAG35343.1; -; mRNA.
DR EMBL; AP003065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP005019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44670.1; -. [O00408-3]
DR CCDS; CCDS53678.1; -. [O00408-4]
DR CCDS; CCDS73345.1; -. [O00408-2]
DR CCDS; CCDS8216.1; -. [O00408-1]
DR RefSeq; NP_001137311.1; NM_001143839.3. [O00408-3]
DR RefSeq; NP_001139681.1; NM_001146209.2. [O00408-4]
DR RefSeq; NP_001230713.1; NM_001243784.1. [O00408-2]
DR RefSeq; NP_002590.1; NM_002599.4. [O00408-1]
DR PDB; 1Z1L; X-ray; 1.70 A; A=578-919.
DR PDB; 3IBJ; X-ray; 3.02 A; A/B=215-900.
DR PDB; 3ITM; X-ray; 2.49 A; A/B/C/D=579-919.
DR PDB; 3ITU; X-ray; 1.58 A; A/B/C/D=579-919.
DR PDB; 4C1I; X-ray; 2.40 A; A/B/C/D=578-921.
DR PDB; 4D08; X-ray; 1.90 A; A/B/C/D=578-921.
DR PDB; 4D09; X-ray; 2.50 A; A/B/C/D=578-921.
DR PDB; 4HTX; X-ray; 1.90 A; A/B/C/D=578-919.
DR PDB; 4HTZ; X-ray; 2.00 A; A/B/C/D=578-919.
DR PDB; 4JIB; X-ray; 1.72 A; A/B/C/D=579-919.
DR PDB; 5TZ3; X-ray; 1.72 A; A/B/C/D=579-919.
DR PDB; 5TZA; X-ray; 1.70 A; A/B/C/D=579-919.
DR PDB; 5TZC; X-ray; 2.36 A; A/B/C/D=579-919.
DR PDB; 5TZH; X-ray; 1.60 A; A/B/C/D=579-919.
DR PDB; 5TZW; X-ray; 1.59 A; A/B/C/D=579-919.
DR PDB; 5TZX; X-ray; 1.90 A; A/B/C/D=579-919.
DR PDB; 5TZZ; X-ray; 1.60 A; A/B/C/D=579-919.
DR PDB; 5U00; X-ray; 1.41 A; A/B/C/D=579-919.
DR PDB; 5U7D; X-ray; 1.75 A; A/B/C=579-919.
DR PDB; 5U7I; X-ray; 2.00 A; A/B/C/D=579-919.
DR PDB; 5U7J; X-ray; 1.90 A; A/B/C/D=579-919.
DR PDB; 5U7K; X-ray; 2.06 A; A/B/C/D=579-919.
DR PDB; 5U7L; X-ray; 2.38 A; A/B/C=579-919.
DR PDB; 5VP0; X-ray; 2.20 A; A/B/C=578-919.
DR PDB; 5VP1; X-ray; 1.86 A; A/B/C=578-919.
DR PDB; 5XKM; X-ray; 2.16 A; A/B/C/D/E/F=578-919.
DR PDB; 6B96; X-ray; 1.88 A; A/B=578-919.
DR PDB; 6B97; X-ray; 1.76 A; A/B=578-919.
DR PDB; 6B98; X-ray; 1.97 A; A/B=578-919.
DR PDB; 6BLF; X-ray; 2.11 A; A/B=578-919.
DR PDB; 6C7D; X-ray; 1.79 A; A/B/C/D=579-917.
DR PDB; 6C7E; X-ray; 1.43 A; A/B/C/D=579-917.
DR PDB; 6C7F; X-ray; 1.82 A; A/B/C=579-917.
DR PDB; 6C7G; X-ray; 1.68 A; A/B/C/D=579-917.
DR PDB; 6C7I; X-ray; 1.71 A; A/B/C/D=579-917.
DR PDB; 6C7J; X-ray; 1.85 A; A/B/C/D=579-917.
DR PDB; 6CYB; X-ray; 1.62 A; A/B=578-919.
DR PDB; 6CYC; X-ray; 1.54 A; A/B=578-919.
DR PDB; 6CYD; X-ray; 1.69 A; A/B=578-919.
DR PDB; 6ZND; X-ray; 2.35 A; A/B=578-921.
DR PDB; 6ZQZ; X-ray; 1.88 A; A/B/C/D=578-921.
DR PDBsum; 1Z1L; -.
DR PDBsum; 3IBJ; -.
DR PDBsum; 3ITM; -.
DR PDBsum; 3ITU; -.
DR PDBsum; 4C1I; -.
DR PDBsum; 4D08; -.
DR PDBsum; 4D09; -.
DR PDBsum; 4HTX; -.
DR PDBsum; 4HTZ; -.
DR PDBsum; 4JIB; -.
DR PDBsum; 5TZ3; -.
DR PDBsum; 5TZA; -.
DR PDBsum; 5TZC; -.
DR PDBsum; 5TZH; -.
DR PDBsum; 5TZW; -.
DR PDBsum; 5TZX; -.
DR PDBsum; 5TZZ; -.
DR PDBsum; 5U00; -.
DR PDBsum; 5U7D; -.
DR PDBsum; 5U7I; -.
DR PDBsum; 5U7J; -.
DR PDBsum; 5U7K; -.
DR PDBsum; 5U7L; -.
DR PDBsum; 5VP0; -.
DR PDBsum; 5VP1; -.
DR PDBsum; 5XKM; -.
DR PDBsum; 6B96; -.
DR PDBsum; 6B97; -.
DR PDBsum; 6B98; -.
DR PDBsum; 6BLF; -.
DR PDBsum; 6C7D; -.
DR PDBsum; 6C7E; -.
DR PDBsum; 6C7F; -.
DR PDBsum; 6C7G; -.
DR PDBsum; 6C7I; -.
DR PDBsum; 6C7J; -.
DR PDBsum; 6CYB; -.
DR PDBsum; 6CYC; -.
DR PDBsum; 6CYD; -.
DR PDBsum; 6ZND; -.
DR PDBsum; 6ZQZ; -.
DR AlphaFoldDB; O00408; -.
DR SMR; O00408; -.
DR BioGRID; 111164; 110.
DR DIP; DIP-40269N; -.
DR ELM; O00408; -.
DR IntAct; O00408; 6.
DR STRING; 9606.ENSP00000334910; -.
DR BindingDB; O00408; -.
DR ChEMBL; CHEMBL2652; -.
DR DrugBank; DB07954; 3-isobutyl-1-methyl-7H-xanthine.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB02315; Cyclic GMP.
DR DrugBank; DB06246; Exisulind.
DR DrugBank; DB05142; ND7001.
DR DrugBank; DB08811; Tofisopam.
DR DrugBank; DB09283; Trapidil.
DR DrugCentral; O00408; -.
DR GuidetoPHARMACOLOGY; 1297; -.
DR iPTMnet; O00408; -.
DR PhosphoSitePlus; O00408; -.
DR SwissPalm; O00408; -.
DR BioMuta; PDE2A; -.
DR EPD; O00408; -.
DR jPOST; O00408; -.
DR MassIVE; O00408; -.
DR MaxQB; O00408; -.
DR PaxDb; O00408; -.
DR PeptideAtlas; O00408; -.
DR PRIDE; O00408; -.
DR ProteomicsDB; 28099; -.
DR ProteomicsDB; 47868; -. [O00408-1]
DR ProteomicsDB; 47869; -. [O00408-4]
DR ProteomicsDB; 67904; -.
DR Antibodypedia; 4059; 373 antibodies from 36 providers.
DR DNASU; 5138; -.
DR Ensembl; ENST00000334456.10; ENSP00000334910.5; ENSG00000186642.16. [O00408-1]
DR Ensembl; ENST00000376450.7; ENSP00000365633.3; ENSG00000186642.16. [O00408-5]
DR Ensembl; ENST00000444035.6; ENSP00000411657.3; ENSG00000186642.16. [O00408-2]
DR Ensembl; ENST00000540345.5; ENSP00000446399.1; ENSG00000186642.16. [O00408-4]
DR Ensembl; ENST00000544570.5; ENSP00000442256.1; ENSG00000186642.16. [O00408-3]
DR GeneID; 5138; -.
DR KEGG; hsa:5138; -.
DR MANE-Select; ENST00000334456.10; ENSP00000334910.5; NM_002599.5; NP_002590.1.
DR UCSC; uc001osn.4; human. [O00408-1]
DR CTD; 5138; -.
DR DisGeNET; 5138; -.
DR GeneCards; PDE2A; -.
DR HGNC; HGNC:8777; PDE2A.
DR HPA; ENSG00000186642; Tissue enhanced (lymphoid).
DR MalaCards; PDE2A; -.
DR MIM; 602658; gene.
DR MIM; 619150; phenotype.
DR neXtProt; NX_O00408; -.
DR OpenTargets; ENSG00000186642; -.
DR Orphanet; 31709; Infantile convulsions and choreoathetosis.
DR PharmGKB; PA33125; -.
DR VEuPathDB; HostDB:ENSG00000186642; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000159817; -.
DR HOGENOM; CLU_006980_3_1_1; -.
DR OMA; ARPAEPX; -.
DR OrthoDB; 1295141at2759; -.
DR PhylomeDB; O00408; -.
DR TreeFam; TF316499; -.
DR BRENDA; 3.1.4.17; 2681.
DR PathwayCommons; O00408; -.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SignaLink; O00408; -.
DR BioGRID-ORCS; 5138; 10 hits in 1074 CRISPR screens.
DR ChiTaRS; PDE2A; human.
DR EvolutionaryTrace; O00408; -.
DR GeneWiki; PDE2A; -.
DR GenomeRNAi; 5138; -.
DR Pharos; O00408; Tclin.
DR PRO; PR:O00408; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O00408; protein.
DR Bgee; ENSG00000186642; Expressed in spleen and 144 other tissues.
DR ExpressionAtlas; O00408; baseline and differential.
DR Genevisible; O00408; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA: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; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; 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; 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: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:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0042301; F:phosphate ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0030911; F:TPR domain binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035904; P:aorta development; ISS:BHF-UCL.
DR GO; GO:0019933; P:cAMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; IDA:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; IDA:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IDA:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IDA:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:UniProtKB.
DR GO; GO:0046069; P:cGMP catabolic process; IDA:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0003170; P:heart valve development; ISS:BHF-UCL.
DR GO; GO:0030224; P:monocyte differentiation; IEP:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IMP: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; IDA:UniProtKB.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP: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; IMP:UniProtKB.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0010752; P:regulation of cGMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0003281; P:ventricular septum development; ISS:BHF-UCL.
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; Disease variant; Hydrolase;
KW Intellectual disability; Lipoprotein; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Mitochondrion outer membrane;
KW Myristate; Nucleotide-binding; Palmitate; Reference proteome; Repeat; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..941
FT /note="cGMP-dependent 3',5'-cyclic phosphodiesterase"
FT /id="PRO_0000198796"
FT DOMAIN 241..377
FT /note="GAF 1"
FT /evidence="ECO:0000255"
FT DOMAIN 409..548
FT /note="GAF 2"
FT /evidence="ECO:0000255"
FT DOMAIN 578..902
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 16..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 656
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 431
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 446
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 465
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 488
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 499
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 660
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15938621,
FT ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287,
FT ECO:0007744|PDB:1Z1L, ECO:0007744|PDB:3IBJ,
FT ECO:0007744|PDB:3ITM, ECO:0007744|PDB:3ITU,
FT ECO:0007744|PDB:4HTX, ECO:0007744|PDB:4HTZ,
FT ECO:0007744|PDB:4JIB"
FT BINDING 696
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15938621,
FT ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287,
FT ECO:0007744|PDB:1Z1L, ECO:0007744|PDB:3ITM,
FT ECO:0007744|PDB:3ITU, ECO:0007744|PDB:4HTX,
FT ECO:0007744|PDB:4HTZ, ECO:0007744|PDB:4JIB"
FT BINDING 697
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15938621,
FT ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287,
FT ECO:0007744|PDB:1Z1L, ECO:0007744|PDB:3IBJ,
FT ECO:0007744|PDB:3ITU, ECO:0007744|PDB:4HTX,
FT ECO:0007744|PDB:4HTZ, ECO:0007744|PDB:4JIB"
FT BINDING 697
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15938621,
FT ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287,
FT ECO:0007744|PDB:1Z1L, ECO:0007744|PDB:3IBJ,
FT ECO:0007744|PDB:3ITM, ECO:0007744|PDB:3ITU,
FT ECO:0007744|PDB:4HTX, ECO:0007744|PDB:4HTZ,
FT ECO:0007744|PDB:4JIB"
FT BINDING 808
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15938621,
FT ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287,
FT ECO:0007744|PDB:1Z1L, ECO:0007744|PDB:3IBJ,
FT ECO:0007744|PDB:3ITM, ECO:0007744|PDB:3ITU,
FT ECO:0007744|PDB:4HTX, ECO:0007744|PDB:4HTZ,
FT ECO:0007744|PDB:4JIB"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:19632989,
FT ECO:0000269|PubMed:20213681"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:19632989"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:19632989"
FT VAR_SEQ 1..48
FT /note="MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPPPQPCADSLQ ->
FT MRRQPAASLDPLAKEPGPPGSRDDRLE (in isoform PDE2A1 and isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_055315"
FT VAR_SEQ 1..24
FT /note="MGQACGHSILCRSQQYPAARPAEP -> MVLVLHHILIAVVQFLR (in
FT isoform PDE2A2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_055316"
FT VAR_SEQ 1..24
FT /note="MGQACGHSILCRSQQYPAARPAEP -> MKKQRIQEGKSLAHR (in
FT isoform PDE2A4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_055317"
FT VAR_SEQ 109..357
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055318"
FT VAR_SEQ 750..807
FT /note="SRKDYQRMLDLMRDIILATDLAHHLRIFKDLQKMAEVGYDRNNKQHHRLLLC
FT LLMTSC -> PLRTTTILMVGLGPGGYRGPRKKLPEGQLSALQRGALGRSRMGLMGRRD
FT PRTGRQAQV (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055319"
FT VAR_SEQ 808..941
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055320"
FT VARIANT 149
FT /note="P -> L (in IDDPADS; unknown pathological
FT significance; dbSNP:rs987916591)"
FT /evidence="ECO:0000269|PubMed:32467598"
FT /id="VAR_085242"
FT VARIANT 224
FT /note="T -> I (in dbSNP:rs341047)"
FT /id="VAR_024170"
FT VARIANT 394..941
FT /note="Missing (in IDDPADS)"
FT /evidence="ECO:0000269|PubMed:32467598"
FT /id="VAR_085243"
FT VARIANT 480
FT /note="D -> G (in IDDPADS; unknown pathological
FT significance; loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity; loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity)"
FT /evidence="ECO:0000269|PubMed:29392776"
FT /id="VAR_085244"
FT MUTAGEN 811
FT /note="D->A: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. No effect on 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 812
FT /note="Q->I: No effect on 3',5'-cyclic-AMP
FT phosphodiesterase activity. Decreased 3',5'-cyclic-GMP
FT phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 812
FT /note="Q->P: Loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 819
FT /note="T->Y: Loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 826
FT /note="I->V: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. Increased 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 827
FT /note="Y->A: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 827
FT /note="Y->F: Loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity. Decreased 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 827
FT /note="Y->V,M: Loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 847
FT /note="M->L: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 858
FT /note="L->M: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. Decreased 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 858
FT /note="L->S: Loss of 3',5'-cyclic-AMP phosphodiesterase
FT activity. Decreased 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT MUTAGEN 907
FT /note="L->A: Decreased 3',5'-cyclic-AMP phosphodiesterase
FT activity. Loss of 3',5'-cyclic-GMP phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:15938621"
FT CONFLICT 38
FT /note="P -> L (in Ref. 2; AAS75513)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="H -> R (in Ref. 3; BAG35343)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="T -> A (in Ref. 2; AAS75513)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="V -> A (in Ref. 2; AAS75513)"
FT /evidence="ECO:0000305"
FT HELIX 226..236
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 242..256
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 282..291
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 297..302
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 313..323
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 342..355
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 362..403
FT /evidence="ECO:0007829|PDB:3IBJ"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 413..425
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 427..435
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 437..443
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 456..460
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 464..472
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 502..506
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:3IBJ"
FT STRAND 516..528
FT /evidence="ECO:0007829|PDB:3IBJ"
FT TURN 531..534
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 535..570
FT /evidence="ECO:0007829|PDB:3IBJ"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:3IBJ"
FT HELIX 579..587
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 593..596
FT /evidence="ECO:0007829|PDB:5U00"
FT TURN 598..601
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 607..609
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 612..614
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 615..625
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 628..631
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 636..648
FT /evidence="ECO:0007829|PDB:5U00"
FT STRAND 654..657
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 658..675
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 677..679
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 683..695
FT /evidence="ECO:0007829|PDB:5U00"
FT TURN 696..699
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 705..710
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 714..719
FT /evidence="ECO:0007829|PDB:5U00"
FT TURN 720..722
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 725..738
FT /evidence="ECO:0007829|PDB:5U00"
FT TURN 741..743
FT /evidence="ECO:0007829|PDB:6B98"
FT TURN 745..748
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 751..766
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 770..786
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 793..808
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 810..813
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 816..839
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 846..848
FT /evidence="ECO:0007829|PDB:5U00"
FT TURN 850..852
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 855..865
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 867..877
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 879..881
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 882..898
FT /evidence="ECO:0007829|PDB:5U00"
FT HELIX 899..902
FT /evidence="ECO:0007829|PDB:5U00"
FT STRAND 904..906
FT /evidence="ECO:0007829|PDB:6CYC"
FT HELIX 914..916
FT /evidence="ECO:0007829|PDB:6C7E"
SQ SEQUENCE 941 AA; 105717 MW; 9797609B487FD64E CRC64;
MGQACGHSIL CRSQQYPAAR PAEPRGQQVF LKPDEPPPPP QPCADSLQDA LLSLGSVIDI
SGLQRAVKEA LSAVLPRVET VYTYLLDGES QLVCEDPPHE LPQEGKVREA IISQKRLGCN
GLGFSDLPGK PLARLVAPLA PDTQVLVMPL ADKEAGAVAA VILVHCGQLS DNEEWSLQAV
EKHTLVALRR VQVLQQRGPR EAPRAVQNPP EGTAEDQKGG AAYTDRDRKI LQLCGELYDL
DASSLQLKVL QYLQQETRAS RCCLLLVSED NLQLSCKVIG DKVLGEEVSF PLTGCLGQVV
EDKKSIQLKD LTSEDVQQLQ SMLGCELQAM LCVPVISRAT DQVVALACAF NKLEGDLFTD
EDEHVIQHCF HYTSTVLTST LAFQKEQKLK CECQALLQVA KNLFTHLDDV SVLLQEIITE
ARNLSNAEIC SVFLLDQNEL VAKVFDGGVV DDESYEIRIP ADQGIAGHVA TTGQILNIPD
AYAHPLFYRG VDDSTGFRTR NILCFPIKNE NQEVIGVAEL VNKINGPWFS KFDEDLATAF
SIYCGISIAH SLLYKKVNEA QYRSHLANEM MMYHMKVSDD EYTKLLHDGI QPVAAIDSNF
ASFTYTPRSL PEDDTSMAIL SMLQDMNFIN NYKIDCPTLA RFCLMVKKGY RDPPYHNWMH
AFSVSHFCYL LYKNLELTNY LEDIEIFALF ISCMCHDLDH RGTNNSFQVA SKSVLAALYS
SEGSVMERHH FAQAIAILNT HGCNIFDHFS RKDYQRMLDL MRDIILATDL AHHLRIFKDL
QKMAEVGYDR NNKQHHRLLL CLLMTSCDLS DQTKGWKTTR KIAELIYKEF FSQGDLEKAM
GNRPMEMMDR EKAYIPELQI SFMEHIAMPI YKLLQDLFPK AAELYERVAS NREHWTKVSH
KFTIRGLPSN NSLDFLDEEY EVPDLDGTRA PINGCCSLDA E
