ID   PDE3B_MOUSE             Reviewed;        1100 AA.
AC   Q61409; Q8CIX5; Q9Z1J9;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 2.
DT   24-JAN-2024, entry version 157.
DE   RecName: Full=cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B {ECO:0000305|PubMed:10454575};
DE            EC=3.1.4.17 {ECO:0000269|PubMed:10454575};
DE   AltName: Full=CGIPDE1;
DE   AltName: Full=Cyclic GMP-inhibited phosphodiesterase B;
DE            Short=CGI-PDE B;
GN   Name=Pde3b {ECO:0000312|MGI:MGI:1333863};
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]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP   LOCATION, PHOSPHORYLATION AT SER-273, AND MUTAGENESIS OF SER-273.
RX   PubMed=10454575; DOI=10.1128/mcb.19.9.6286;
RA   Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K.,
RA   Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M.;
RT   "Insulin-induced phosphorylation and activation of cyclic nucleotide
RT   phosphodiesterase 3B by the serine-threonine kinase Akt.";
RL   Mol. Cell. Biol. 19:6286-6296(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 287-1085, AND TISSUE SPECIFICITY.
RC   STRAIN=SWR/J; TISSUE=Adipose tissue;
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   FUNCTION, AND INTERACTION WITH PIK3CG.
RX   PubMed=15294162; DOI=10.1016/j.cell.2004.07.017;
RA   Patrucco E., Notte A., Barberis L., Selvetella G., Maffei A.,
RA   Brancaccio M., Marengo S., Russo G., Azzolino O., Rybalkin S.D.,
RA   Silengo L., Altruda F., Wetzker R., Wymann M.P., Lembo G., Hirsch E.;
RT   "PI3Kgamma modulates the cardiac response to chronic pressure overload by
RT   distinct kinase-dependent and -independent effects.";
RL   Cell 118:375-387(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-273 AND SER-274, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, and Liver;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   INTERACTION WITH ABHD15.
RX   PubMed=29768196; DOI=10.1016/j.celrep.2018.04.055;
RA   Xia W., Pessentheiner A.R., Hofer D.C., Amor M., Schreiber R.,
RA   Schoiswohl G., Eichmann T.O., Walenta E., Itariu B., Prager G., Hackl H.,
RA   Stulnig T., Kratky D., Ruelicke T., Bogner-Strauss J.G.;
RT   "Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering
RT   PDE3B Stability and Contributes to Insulin Resistance.";
RL   Cell Rep. 23:1948-1961(2018).
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 processes (PubMed:10454575). Regulates
CC       angiogenesis by inhibiting the cAMP-dependent guanine nucleotide
CC       exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase
CC       gamma-mediated signaling (By similarity). Controls cardiac
CC       contractility by reducing cAMP concentration in cardiocytes
CC       (PubMed:15294162). {ECO:0000250|UniProtKB:Q13370,
CC       ECO:0000269|PubMed:10454575, ECO:0000269|PubMed:15294162}.
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:10454575};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC         Evidence={ECO:0000305|PubMed:10454575};
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:10454575};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000305|PubMed:10454575};
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:0000250|UniProtKB:Q13370};
CC       Note=Binds 2 divalent metal cations per subunit.
CC       {ECO:0000250|UniProtKB:Q13370};
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 (By similarity). Interacts with PIK3CG; regulates
CC       PDE3B activity and thereby cAMP levels in cells (PubMed:15294162).
CC       Interacts with RAPGEF3 and PIK3R6; form a signaling complex that
CC       regulates phosphatidylinositol 3-kinase gamma in angiogenesis (By
CC       similarity). Interacts with ABHD15; this interaction regulates PDE3B's
CC       stability and expression and, thereby, impacts the antilipolytic action
CC       of insulin (PubMed:29768196). {ECO:0000250|UniProtKB:Q13370,
CC       ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:29768196}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10454575}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Abundant in adipose tissues.
CC       {ECO:0000269|PubMed:8921398}.
CC   -!- PTM: Phosphorylation at Ser-273 mediates insulin-induced activation of
CC       PDE3B. {ECO:0000269|PubMed:10454575}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       PDE3 subfamily. {ECO:0000305}.
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DR   EMBL; AJ132271; CAA10639.1; -; mRNA.
DR   EMBL; AF547435; AAN52086.1; -; mRNA.
DR   EMBL; X95521; CAA64775.1; -; mRNA.
DR   RefSeq; NP_035185.2; NM_011055.2.
DR   AlphaFoldDB; Q61409; -.
DR   SMR; Q61409; -.
DR   STRING; 10090.ENSMUSP00000032909; -.
DR   iPTMnet; Q61409; -.
DR   PhosphoSitePlus; Q61409; -.
DR   EPD; Q61409; -.
DR   jPOST; Q61409; -.
DR   MaxQB; Q61409; -.
DR   PaxDb; 10090-ENSMUSP00000032909; -.
DR   ProteomicsDB; 287805; -.
DR   DNASU; 18576; -.
DR   GeneID; 18576; -.
DR   KEGG; mmu:18576; -.
DR   AGR; MGI:1333863; -.
DR   CTD; 5140; -.
DR   MGI; MGI:1333863; Pde3b.
DR   eggNOG; ENOG502QSV8; Eukaryota.
DR   InParanoid; Q61409; -.
DR   OrthoDB; 5479253at2759; -.
DR   PhylomeDB; Q61409; -.
DR   Reactome; R-MMU-165160; PDE3B signalling.
DR   Reactome; R-MMU-418555; G alpha (s) signalling events.
DR   BioGRID-ORCS; 18576; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Pde3b; mouse.
DR   PRO; PR:Q61409; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q61409; Protein.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR   GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; ISO:MGI.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR   GO; GO:0043422; F:protein kinase B binding; IPI:BHF-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IEP:BHF-UCL.
DR   GO; GO:0031018; P:endocrine pancreas development; IDA:MGI.
DR   GO; GO:0042593; P:glucose homeostasis; IDA:MGI.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR   GO; GO:0007162; P:negative regulation of cell adhesion; ISO:MGI.
DR   GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:MGI.
DR   GO; GO:0045765; P:regulation of angiogenesis; ISO:MGI.
DR   GO; GO:0050796; P:regulation of insulin secretion; IDA:MGI.
DR   GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI.
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   Angiogenesis; cAMP; cGMP; Coiled coil; Hydrolase; Magnesium; Membrane;
KW   Metal-binding; Phosphoprotein; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..1100
FT                   /note="cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B"
FT                   /id="PRO_0000198803"
FT   TRANSMEM        69..89
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        110..130
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        140..160
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        170..190
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        198..218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          627..1061
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1..28
FT                   /note="Interaction with RAPGEF3"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   REGION          400..423
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          415..439
FT                   /note="Interaction with PIK3R6"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   REGION          570..590
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          993..1033
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          1044..1079
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        409..423
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        573..587
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        993..1023
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        713
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O76083"
FT   BINDING         713
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         717
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   BINDING         797
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   BINDING         798
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         798
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   BINDING         798
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   BINDING         913
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   BINDING         913
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   BINDING         964
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q14432"
FT   MOD_RES         15
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         273
FT                   /note="Phosphoserine; by PKB/AKT1 or PKB/AKT2"
FT                   /evidence="ECO:0000269|PubMed:10454575,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         274
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         421
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13370"
FT   MUTAGEN         273
FT                   /note="S->A: Loss of insulin-induced phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:10454575"
FT   CONFLICT        10
FT                   /note="A -> T (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        261
FT                   /note="E -> D (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        288..290
FT                   /note="SGK -> IPE (in Ref. 3; CAA64775)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        439
FT                   /note="S -> G (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        444
FT                   /note="Y -> H (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        465
FT                   /note="F -> M (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        756
FT                   /note="G -> S (in Ref. 1; CAA10639)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        944
FT                   /note="A -> T (in Ref. 1; CAA10639 and 3; CAA64775)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1082
FT                   /note="A -> T (in Ref. 3; CAA64775)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1100 AA;  122154 MW;  92E36B28D4A5FDF1 CRC64;
     MRKDERERDA PAMRSPPPPP ASAASPPESL RNGYVKSCVS PLRQDPPRSF FFHLCRFCNV
     EPPAASLRAG ARLSLGVLAA FVLAALLGAR PERWAAAAAG LRTLLSACSL SLSPLFSIAC
     AFFFLTCFLT RAQRGPGRGA GSWWLLALPA CCYLGDFAAW QWWSWLRGEP AAAGRLCLVL
     SCVGLLTLAP RVRLRHGVLV LLFAGLVWWV SFSGLGALPP ALRPLLSCLV GGAGCLLALG
     LDHFFHVRGA SPPPRSASTA EEKVPVIRPR RRSSCVSLGE SAAGYYGSGK MFRRPSLPCI
     SREQMILWDW DLKQWCKPHY QNSGGGNGVD LSVLNEARNM VSDLLIDPSL PPQVISSLRS
     ISSLMGAFSG SCRPKINSFT PFPGFYPCSE VEDPVEKGDR KLHKGLSGRT SFPTPQLRRS
     SGASSLLTNE HCSRWDRSSG KRSYQELSVS SHGCHLNGPF SSNLFTIPKQ RSSSVSLTHH
     AGLRRAGALP SHSLLNSSSH VPVSAGSLTN RSPIGFPDTT DFLTKPNIIL HRSLGSVSSA
     ADFHQYLRNS DSNLCSSCGH QILKYVSTCE PDGTDHPSEK SGEEDSSVFS KEPLNIVETQ
     EEETMKKACR ELFLEGDSHL MEEAQQPNID QEVSLDPMLV EDYDSLIEKM NNWNFQIFEL
     VEKMGEKSGR ILSQVMYTLF QDTGLLETFK IPTQEFMNYF RALENGYRDI PYHNRVHATD
     VLHAVWYLTT RPIPGLPQIH NNHETETKAD SDGRLGSGQI AYISSKSCCI PDMSYGCLSS
     NIPALELMAL YVAAAMHDYD HPGRTNAFLV ATNAPQAVLY NDRSVLENHH AASAWNLYLS
     RPEYNFLLNL DHMEFKRFRF LVIEAILATD LKKHFDFLAE FNAKANDVNS NGIEWSSEND
     RLLVCQVCIK LADINGPAKD RDLHLRWTEG IVNEFYEQGD EEAALGLPIS PFMDRSSPQL
     AKLQESFITH IVGPLCNSYD AAGLLPGQWI ETEEGDDTES DDDDDDDDGD GGEELDSDDE
     ETEDNLNPKP QRRKGRRRIF CQLMHHLTEN HKIWKEIIEE EEEKCKAEGN KLQVDNASLP
     QADEIQVIEE ADEEEEQMFE
//