ID   PDE3B_HUMAN             Reviewed;        1112 AA.
AC   Q13370; B7ZM37; O00639; Q14408; Q6SEI4;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 2.
DT   27-MAR-2024, entry version 205.
DE   RecName: Full=cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B {ECO:0000305|PubMed:14592490};
DE            EC=3.1.4.17 {ECO:0000269|PubMed:14592490};
DE   AltName: Full=CGIPDE1 {ECO:0000303|PubMed:8884271};
DE            Short=CGIP1 {ECO:0000303|PubMed:8884271};
DE   AltName: Full=Cyclic GMP-inhibited phosphodiesterase B;
DE            Short=CGI-PDE B;
GN   Name=PDE3B {ECO:0000312|HGNC:HGNC:8779};
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Adipose tissue;
RX   PubMed=8884271; DOI=10.1006/geno.1996.0493;
RA   Miki T., Taira M., Hockman S., Shimada F., Lieman J., Napolitano M.,
RA   Ward D., Taira M., Makino H., Manganiello V.C.;
RT   "Characterization of the cDNA and gene encoding human PDE3B, the cGIP1
RT   isoform of the human cyclic GMP-inhibited cyclic nucleotide
RT   phosphodiesterase family.";
RL   Genomics 36:476-485(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8706823; DOI=10.1016/0014-5793(96)00410-3;
RA   Murata T., Taira M., Manganiello V.C.;
RT   "Differential expression of cGMP-inhibited cyclic nucleotide
RT   phosphodiesterases in human hepatoma cell lines.";
RL   FEBS Lett. 390:29-33(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-87.
RX   PubMed=8921398; DOI=10.1006/geno.1996.0544;
RA   Loebbert R.W., Winterpacht A., Seipel B., Zabel B.U.;
RT   "Molecular cloning and chromosomal assignment of the human homologue of the
RT   rat cGMP-inhibited phosphodiesterase 1 (PDE3A) -- a gene involved in fat
RT   metabolism located at 11p15.1.";
RL   Genomics 37:211-218(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=16702214; DOI=10.1074/jbc.m601307200;
RA   Liu H., Tang J.R., Choi Y.H., Napolitano M., Hockman S., Taira M.,
RA   Degerman E., Manganiello V.C.;
RT   "Importance of cAMP-response element-binding protein in regulation of
RT   expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b)
RT   gene in differentiating 3T3-L1 preadipocytes.";
RL   J. Biol. Chem. 281:21096-21113(2006).
RN   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=14592490; DOI=10.1016/j.bmcl.2003.08.056;
RA   Edmondson S.D., Mastracchio A., He J., Chung C.C., Forrest M.J.,
RA   Hofsess S., MacIntyre E., Metzger J., O'Connor N., Patel K., Tong X.,
RA   Tota M.R., Van der Ploeg L.H., Varnerin J.P., Fisher M.H., Wyvratt M.J.,
RA   Weber A.E., Parmee E.R.;
RT   "Benzyl vinylogous amide substituted aryldihydropyridazinones and
RT   aryldimethylpyrazolones as potent and selective PDE3B inhibitors.";
RL   Bioorg. Med. Chem. Lett. 13:3983-3987(2003).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [11]
RP   FUNCTION, INTERACTION WITH RAPGEF3 AND PIK3R6, REGION, AND MUTAGENESIS OF
RP   ARG-2; ARG-3; ARG-6; ALA-8; LYS-9; ALA-10; ARG-12; ARG-439; ARG-440;
RP   SER-445 AND PRO-449.
RX   PubMed=21393242; DOI=10.1074/jbc.m110.217026;
RA   Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M.,
RA   Houslay M.D., Maurice D.H.;
RT   "A phosphodiesterase 3B-based signaling complex integrates exchange protein
RT   activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human
RT   arterial endothelial cells.";
RL   J. Biol. Chem. 286:16285-16296(2011).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [14] {ECO:0007744|PDB:1SO2, ECO:0007744|PDB:1SOJ}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 654-1073 IN COMPLEX WITH
RP   MAGNESIUM AND INHIBITORS, COFACTOR, AND SUBUNIT.
RX   PubMed=15147193; DOI=10.1021/bi049868i;
RA   Scapin G., Patel S.B., Chung C., Varnerin J.P., Edmondson S.D.,
RA   Mastracchio A., Parmee E.R., Singh S.B., Becker J.W., Van der Ploeg L.H.,
RA   Tota M.R.;
RT   "Crystal structure of human phosphodiesterase 3B: atomic basis for
RT   substrate and inhibitor specificity.";
RL   Biochemistry 43:6091-6100(2004).
CC   -!- FUNCTION: Cyclic nucleotide phosphodiesterase with a dual-specificity
CC       for the second messengers cAMP and cGMP, which are key regulators of
CC       many important physiological process (PubMed:14592490,
CC       PubMed:21393242). Regulates angiogenesis by inhibiting the cAMP-
CC       dependent guanine nucleotide exchange factor RAPGEF3 and downstream
CC       phosphatidylinositol 3-kinase gamma-mediated signaling
CC       (PubMed:21393242). Controls cardiac contractility by reducing cAMP
CC       concentration in cardiocytes (By similarity).
CC       {ECO:0000250|UniProtKB:Q61409, ECO:0000269|PubMed:14592490,
CC       ECO:0000269|PubMed:21393242}.
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:14592490};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC         Evidence={ECO:0000305|PubMed:14592490};
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:14592490};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000305|PubMed:14592490};
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:0000250|UniProtKB:Q63085};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC         Evidence={ECO:0000250|UniProtKB:Q63085};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:15147193};
CC       Note=Binds 2 divalent metal cations per subunit.
CC       {ECO:0000269|PubMed:15147193};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:Q14432};
CC       Note=Binds 2 divalent metal cations per subunit.
CC       {ECO:0000250|UniProtKB:Q14432};
CC   -!- ACTIVITY REGULATION: Inhibited by cGMP. {ECO:0000250|UniProtKB:Q63085}.
CC   -!- SUBUNIT: Homodimer (PubMed:15147193). Interacts with PIK3CG; regulates
CC       PDE3B activity and thereby cAMP levels in cells (By similarity).
CC       Interacts with RAPGEF3 and PIK3R6; form a signaling complex that
CC       regulates phosphatidylinositol 3-kinase gamma in angiogenesis
CC       (PubMed:21393242). Interacts with ABHD15; this interaction regulates
CC       PDE3B's stability and expression and, thereby, impacts the
CC       antilipolytic action of insulin (By similarity).
CC       {ECO:0000250|UniProtKB:Q61409, ECO:0000269|PubMed:15147193,
CC       ECO:0000269|PubMed:21393242}.
CC   -!- INTERACTION:
CC       Q13370; O60760: HPGDS; NbExp=3; IntAct=EBI-6172856, EBI-10187349;
CC       Q13370; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-6172856, EBI-739832;
CC       Q13370; P48736: PIK3CG; NbExp=3; IntAct=EBI-6172856, EBI-1030384;
CC       Q13370; Q5UE93: PIK3R6; NbExp=3; IntAct=EBI-6172856, EBI-6172907;
CC       Q13370; O95398: RAPGEF3; NbExp=8; IntAct=EBI-6172856, EBI-6172806;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q61409}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13370-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q13370-2; Sequence=VSP_054138;
CC   -!- TISSUE SPECIFICITY: Abundant in adipose tissues.
CC       {ECO:0000269|PubMed:8884271}.
CC   -!- PTM: Phosphorylation at Ser-295 mediates insulin-induced activation of
CC       PDE3B. {ECO:0000250|UniProtKB:Q61409}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       PDE3 subfamily. {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; U38178; AAC50724.1; -; Genomic_DNA.
DR   EMBL; D50640; BAA09306.1; -; Genomic_DNA.
DR   EMBL; X95520; CAA64774.1; -; mRNA.
DR   EMBL; AY459346; AAR24292.1; -; mRNA.
DR   EMBL; AC018795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC087207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471064; EAW68474.1; -; Genomic_DNA.
DR   EMBL; BC136565; AAI36566.1; -; mRNA.
DR   EMBL; BC136566; AAI36567.1; -; mRNA.
DR   EMBL; BC144248; AAI44249.1; -; mRNA.
DR   CCDS; CCDS7817.1; -. [Q13370-1]
DR   CCDS; CCDS91445.1; -. [Q13370-2]
DR   PIR; S70522; S70522.
DR   RefSeq; NP_000913.2; NM_000922.3. [Q13370-1]
DR   PDB; 1SO2; X-ray; 2.40 A; A/B/C/D=654-1073.
DR   PDB; 1SOJ; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=654-1073.
DR   PDBsum; 1SO2; -.
DR   PDBsum; 1SOJ; -.
DR   AlphaFoldDB; Q13370; -.
DR   SMR; Q13370; -.
DR   BioGRID; 111166; 122.
DR   IntAct; Q13370; 26.
DR   STRING; 9606.ENSP00000282096; -.
DR   BindingDB; Q13370; -.
DR   ChEMBL; CHEMBL290; -.
DR   DrugBank; DB07954; 3-isobutyl-1-methyl-7H-xanthine.
DR   DrugBank; DB01640; 6-(4-{[2-(3-iodobenzyl)-3-oxocyclohex-1-en-1-yl]amino}phenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one.
DR   DrugBank; DB01427; Amrinone.
DR   DrugBank; DB00201; Caffeine.
DR   DrugBank; DB01970; Hg9a-9, Nonanoyl-N-Hydroxyethylglucamide.
DR   DrugBank; DB01113; Papaverine.
DR   DrugBank; DB09283; Trapidil.
DR   DrugCentral; Q13370; -.
DR   GuidetoPHARMACOLOGY; 1299; -.
DR   iPTMnet; Q13370; -.
DR   PhosphoSitePlus; Q13370; -.
DR   SwissPalm; Q13370; -.
DR   BioMuta; PDE3B; -.
DR   DMDM; 143811435; -.
DR   EPD; Q13370; -.
DR   jPOST; Q13370; -.
DR   MassIVE; Q13370; -.
DR   MaxQB; Q13370; -.
DR   PaxDb; 9606-ENSP00000282096; -.
DR   PeptideAtlas; Q13370; -.
DR   ProteomicsDB; 59354; -. [Q13370-1]
DR   ProteomicsDB; 7244; -.
DR   Pumba; Q13370; -.
DR   Antibodypedia; 4012; 252 antibodies from 31 providers.
DR   DNASU; 5140; -.
DR   Ensembl; ENST00000282096.9; ENSP00000282096.4; ENSG00000152270.9. [Q13370-1]
DR   Ensembl; ENST00000455098.2; ENSP00000388644.2; ENSG00000152270.9. [Q13370-2]
DR   GeneID; 5140; -.
DR   KEGG; hsa:5140; -.
DR   MANE-Select; ENST00000282096.9; ENSP00000282096.4; NM_000922.4; NP_000913.2.
DR   UCSC; uc001mln.4; human. [Q13370-1]
DR   AGR; HGNC:8779; -.
DR   CTD; 5140; -.
DR   DisGeNET; 5140; -.
DR   GeneCards; PDE3B; -.
DR   HGNC; HGNC:8779; PDE3B.
DR   HPA; ENSG00000152270; Tissue enhanced (adipose).
DR   MIM; 602047; gene.
DR   neXtProt; NX_Q13370; -.
DR   OpenTargets; ENSG00000152270; -.
DR   PharmGKB; PA33127; -.
DR   VEuPathDB; HostDB:ENSG00000152270; -.
DR   eggNOG; ENOG502QSV8; Eukaryota.
DR   GeneTree; ENSGT00940000159336; -.
DR   HOGENOM; CLU_008844_1_0_1; -.
DR   InParanoid; Q13370; -.
DR   OMA; GRRQIFC; -.
DR   OrthoDB; 5479253at2759; -.
DR   PhylomeDB; Q13370; -.
DR   TreeFam; TF329631; -.
DR   BRENDA; 3.1.4.17; 2681.
DR   PathwayCommons; Q13370; -.
DR   Reactome; R-HSA-165160; PDE3B signalling.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   SignaLink; Q13370; -.
DR   SIGNOR; Q13370; -.
DR   BioGRID-ORCS; 5140; 12 hits in 1156 CRISPR screens.
DR   ChiTaRS; PDE3B; human.
DR   EvolutionaryTrace; Q13370; -.
DR   GenomeRNAi; 5140; -.
DR   Pharos; Q13370; Tclin.
DR   PRO; PR:Q13370; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q13370; Protein.
DR   Bgee; ENSG00000152270; Expressed in colonic epithelium and 143 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL.
DR   GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:BHF-UCL.
DR   GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:RHEA.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IDA:UniProt.
DR   GO; GO:0004119; F:cGMP-inhibited cyclic-nucleotide phosphodiesterase activity; TAS:ProtInc.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0043422; F:protein kinase B binding; ISS:BHF-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISS:BHF-UCL.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR   GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IBA:GO_Central.
DR   GO; GO:0007162; P:negative regulation of cell adhesion; IMP:BHF-UCL.
DR   GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IC:BHF-UCL.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:BHF-UCL.
DR   GO; GO:0045765; P:regulation of angiogenesis; IMP:UniProt.
DR   GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProt.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
DR   InterPro; IPR003607; HD/PDEase_dom.
DR   InterPro; IPR002073; PDEase_catalytic_dom.
DR   InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR   InterPro; IPR023174; PDEase_CS.
DR   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   PANTHER; PTHR11347:SF29; PHOSPHODIESTERASE; 1.
DR   Pfam; PF00233; PDEase_I; 1.
DR   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
DR   Genevisible; Q13370; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Angiogenesis; cAMP; cGMP; Hydrolase;
KW   Magnesium; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..1112
FT                   /note="cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B"
FT                   /id="PRO_0000198802"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        117..137
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        152..172
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        192..212
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        220..240
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        247..267
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          651..1079
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          1..26
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1..25
FT                   /note="Interaction with RAPGEF3"
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   REGION          418..471
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          436..460
FT                   /note="Interaction with PIK3R6"
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   REGION          1017..1051
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1092..1112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        428..455
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1017..1039
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        737
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O76083"
FT   BINDING         737
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         741
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:15147193,
FT                   ECO:0007744|PDB:1SO2, ECO:0007744|PDB:1SOJ"
FT   BINDING         821
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:15147193,
FT                   ECO:0007744|PDB:1SO2, ECO:0007744|PDB:1SOJ"
FT   BINDING         822
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         822
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:15147193,
FT                   ECO:0007744|PDB:1SO2, ECO:0007744|PDB:1SOJ"
FT   BINDING         822
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:15147193,
FT                   ECO:0007744|PDB:1SO2"
FT   BINDING         937
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         937
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:15147193,
FT                   ECO:0007744|PDB:1SO2, ECO:0007744|PDB:1SOJ"
FT   BINDING         988
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61409"
FT   MOD_RES         295
FT                   /note="Phosphoserine; by PKB/AKT1 or PKB/AKT2"
FT                   /evidence="ECO:0000250|UniProtKB:Q61409"
FT   MOD_RES         296
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61409"
FT   MOD_RES         442
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         376..426
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054138"
FT   VARIANT         87
FT                   /note="A -> V (in dbSNP:rs1056584)"
FT                   /evidence="ECO:0000269|PubMed:8921398"
FT                   /id="VAR_031462"
FT   MUTAGEN         2
FT                   /note="R->A: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         3
FT                   /note="R->A: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         6
FT                   /note="R->A: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         8
FT                   /note="A->D: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         9
FT                   /note="K->A: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         10
FT                   /note="A->D: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         12
FT                   /note="R->A: Loss of interaction with RAPGEF3."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         439
FT                   /note="R->A: Loss of interaction with PIK3R6."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         440
FT                   /note="R->A: Loss of interaction with PIK3R6."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         445
FT                   /note="S->A: Loss of interaction with PIK3R6."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   MUTAGEN         449
FT                   /note="P->A: Loss of interaction with PIK3R6."
FT                   /evidence="ECO:0000269|PubMed:21393242"
FT   CONFLICT        84
FT                   /note="A -> D (in Ref. 1; AAC50724 and 2; BAA09306)"
FT                   /evidence="ECO:0000305"
FT   HELIX           662..674
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           681..688
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           689..694
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           695..706
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           709..712
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           717..728
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   STRAND          735..738
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           739..752
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           802..804
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           808..820
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   TURN            821..824
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           830..835
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           839..843
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   TURN            844..846
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           849..863
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           866..868
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   TURN            870..873
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           876..891
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           895..897
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           898..909
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   STRAND          911..913
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           922..937
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           940..942
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           945..968
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           984..994
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           996..1005
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   STRAND          1012..1015
FT                   /evidence="ECO:0007829|PDB:1SOJ"
FT   STRAND          1055..1058
FT                   /evidence="ECO:0007829|PDB:1SO2"
FT   HELIX           1060..1072
FT                   /evidence="ECO:0007829|PDB:1SO2"
SQ   SEQUENCE   1112 AA;  124333 MW;  55451C3DA142EF6A CRC64;
     MRRDERDAKA MRSLQPPDGA GSPPESLRNG YVKSCVSPLR QDPPRGFFFH LCRFCNVELR
     PPPASPQQPR RCSPFCRARL SLGALAAFVL ALLLGAEPES WAAGAAWLRT LLSVCSHSLS
     PLFSIACAFF FLTCFLTRTK RGPGPGRSCG SWWLLALPAC CYLGDFLVWQ WWSWPWGDGD
     AGSAAPHTPP EAAAGRLLLV LSCVGLLLTL AHPLRLRHCV LVLLLASFVW WVSFTSLGSL
     PSALRPLLSG LVGGAGCLLA LGLDHFFQIR EAPLHPRLSS AAEEKVPVIR PRRRSSCVSL
     GETAASYYGS CKIFRRPSLP CISREQMILW DWDLKQWYKP HYQNSGGGNG VDLSVLNEAR
     NMVSDLLTDP SLPPQVISSL RSISSLMGAF SGSCRPKINP LTPFPGFYPC SEIEDPAEKG
     DRKLNKGLNR NSLPTPQLRR SSGTSGLLPV EQSSRWDRNN GKRPHQEFGI SSQGCYLNGP
     FNSNLLTIPK QRSSSVSLTH HVGLRRAGVL SSLSPVNSSN HGPVSTGSLT NRSPIEFPDT
     ADFLNKPSVI LQRSLGNAPN TPDFYQQLRN SDSNLCNSCG HQMLKYVSTS ESDGTDCCSG
     KSGEEENIFS KESFKLMETQ QEEETEKKDS RKLFQEGDKW LTEEAQSEQQ TNIEQEVSLD
     LILVEEYDSL IEKMSNWNFP IFELVEKMGE KSGRILSQVM YTLFQDTGLL EIFKIPTQQF
     MNYFRALENG YRDIPYHNRI HATDVLHAVW YLTTRPVPGL QQIHNGCGTG NETDSDGRIN
     HGRIAYISSK SCSNPDESYG CLSSNIPALE LMALYVAAAM HDYDHPGRTN AFLVATNAPQ
     AVLYNDRSVL ENHHAASAWN LYLSRPEYNF LLHLDHVEFK RFRFLVIEAI LATDLKKHFD
     FLAEFNAKAN DVNSNGIEWS NENDRLLVCQ VCIKLADING PAKVRDLHLK WTEGIVNEFY
     EQGDEEANLG LPISPFMDRS SPQLAKLQES FITHIVGPLC NSYDAAGLLP GQWLEAEEDN
     DTESGDDEDG EELDTEDEEM ENNLNPKPPR RKSRRRIFCQ LMHHLTENHK IWKEIVEEEE
     KCKADGNKLQ VENSSLPQAD EIQVIEEADE EE
//