PDE3B_MOUSE
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 03-AUG-2022, entry version 149.
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].
RC STRAIN=J125;
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).
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). {ECO:0000250|UniProtKB:Q13370,
CC ECO:0000269|PubMed:15294162}.
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; Q61409; -.
DR PRIDE; Q61409; -.
DR ProteomicsDB; 287805; -.
DR DNASU; 18576; -.
DR GeneID; 18576; -.
DR KEGG; mmu:18576; -.
DR CTD; 5140; -.
DR MGI; MGI:1333863; Pde3b.
DR eggNOG; ENOG502QSV8; Eukaryota.
DR InParanoid; Q61409; -.
DR OrthoDB; 904682at2759; -.
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 73 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0004115; F:3',5'-cyclic-AMP 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:0050796; P:regulation of insulin secretion; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 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 Pfam; PF00233; PDEase_I; 1.
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 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
