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}.
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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 Genevisible; Q13370; HS.
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.
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
//
