PDE3B_RAT
ID PDE3B_RAT Reviewed; 1108 AA.
AC Q63085;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B {ECO:0000305|PubMed:9631240};
DE EC=3.1.4.17 {ECO:0000269|PubMed:9631240};
DE AltName: Full=CGI PDE;
DE AltName: Full=Cyclic GMP-inhibited phosphodiesterase B;
DE Short=CGI-PDE B;
DE AltName: Full=RcGIPl {ECO:0000303|PubMed:8395509};
GN Name=Pde3b {ECO:0000312|RGD:61943};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Adipose tissue;
RX PubMed=8395509; DOI=10.1016/s0021-9258(17)46666-x;
RA Taira M., Hockman S.C., Calvo J.C., Taira M., Belfrage P.,
RA Manganiello V.C.;
RT "Molecular cloning of the rat adipocyte hormone-sensitive cyclic GMP-
RT inhibited cyclic nucleotide phosphodiesterase.";
RL J. Biol. Chem. 268:18573-18579(1993).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Adipose tissue;
RX PubMed=9631240; DOI=10.1007/bf02737830;
RA He R., Komas N., Ekholm D., Murata T., Taira M., Hockman S.C., Degerman E.,
RA Manganiello V.C.;
RT "Expression and characterization of deletion recombinants of two cGMP-
RT inhibited cyclic nucleotide phosphodiesterases (PDE-3).";
RL Cell Biochem. Biophys. 29:89-111(1998).
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:9631240). 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q13370,
CC ECO:0000250|UniProtKB:Q61409, ECO:0000269|PubMed:9631240}.
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:9631240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:9631240};
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:9631240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:9631240};
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:9631240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000305|PubMed:9631240};
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:0000269|PubMed:9631240}.
CC -!- SUBUNIT: Homodimer (By similarity). 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q13370,
CC ECO:0000250|UniProtKB:Q61409}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q61409}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Abundant in adipose tissues.
CC {ECO:0000269|PubMed:8395509}.
CC -!- PTM: Phosphorylation at Ser-279 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; Z22867; CAA80489.1; -; mRNA.
DR PIR; A48508; A48508.
DR RefSeq; NP_058925.1; NM_017229.1.
DR AlphaFoldDB; Q63085; -.
DR SMR; Q63085; -.
DR STRING; 10116.ENSRNOP00000015498; -.
DR iPTMnet; Q63085; -.
DR PhosphoSitePlus; Q63085; -.
DR PaxDb; Q63085; -.
DR PRIDE; Q63085; -.
DR DNASU; 29516; -.
DR GeneID; 29516; -.
DR KEGG; rno:29516; -.
DR UCSC; RGD:61943; rat.
DR CTD; 5140; -.
DR RGD; 61943; Pde3b.
DR eggNOG; ENOG502QSV8; Eukaryota.
DR InParanoid; Q63085; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q63085; -.
DR Reactome; R-RNO-165160; PDE3B signalling.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR SABIO-RK; Q63085; -.
DR PRO; PR:Q63085; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:RGD.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051219; F:phosphoprotein binding; IDA:RGD.
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:0031018; P:endocrine pancreas development; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IMP:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:RGD.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:RGD.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
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; Hydrolase; Magnesium; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..1108
FT /note="cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B"
FT /id="PRO_0000198804"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 633..1070
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..32
FT /note="Interaction with RAPGEF3"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT REGION 405..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..445
FT /note="Interaction with PIK3R6"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT REGION 999..1042
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..27
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 999..1032
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 719
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 719
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 723
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT BINDING 803
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT BINDING 804
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 804
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT BINDING 804
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT BINDING 919
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 919
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
FT BINDING 970
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:0000250|UniProtKB:Q61409"
FT MOD_RES 279
FT /note="Phosphoserine; by PKB/AKT1 or PKB/AKT2"
FT /evidence="ECO:0000250|UniProtKB:Q61409"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61409"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13370"
SQ SEQUENCE 1108 AA; 123107 MW; C9B5078C7D3ADD6D CRC64;
MRKDERERDT PAMRSPPPPP PPATATAASP PESLRNGYVK SCVSPLRQDP PRSFFFHLCR
FCNVEPPAAS LRAGARLSLA ALAAFVLAAL LGAGPERWAA AATGLRTLLS ACSLSLSPLF
SIACAFFFLT CFLTRAQRGP DRGAGSWWLL ALPACCYLGD FAAWQWWSWL RGEPAAAAAG
RLCLVLSCVG LLTLAPRVRL RHGVLVLLFA GLVWWVSFSG LGALPPALRP LLSCLVGGAG
CLLALGLDHF FHVRGASPPP RSASTADEKV PVIRPRRRSS CVSLGESAAG YYGSGKMFRR
PSLPCISREQ MILWDWDLKQ WCKPHYQNSG GGNGVDLSVL NEARNMVSDL LIDPSLPPQV
ISSLRSISSL MGAFSGSCRP KINSFTPFPG FYPCSEVEDP VEKGDRKLHK GLSSKPSFPT
AQLRRSSGAS GLLTSEHHSR WDRSGGKRPY QELSVSSHGC HLNGPFSSNL MTIPKQRSSS
VSLTHHAGLR RAGALPSPSL LNSSSHVPVS AGCLTNRSPV GFLDTSDFLT KPSVTLHRSL
GSVSSAADFH QYLRNSDSSL CSSCGHQILK YVSTCEPDGT DHHNEKSGEE DSTVFSKERL
NIVETQEEET VKEDCRELFL EGDDHLMEEA QQPNIDQEVL LDPMLVEDYD SLIEKMSNWN
FQIFELVEKM GEKSGRILSQ VMYTLFQDTG LLETFKIPTQ EFMNYFRALE NGYRDIPYHN
RVHATDVLHA VWYLTTRPIP GLQQLHNNHE TETKADSDAR LSSGQIAYLS SKSCCIPDKS
YGCLSSNIPA LELMALYVAA AMHDYDHPGR TNAFLVATNA PQAVLYNDRS VLENHHAASA
WNLYLSRPEY NFLLNLDHME FKRFRFLVIE AILATDLKKH FDFLAEFNAK ANDVNSNGIE
WSSENDRLLV CQVCIKLADI NGPAKDRDLH LRWTEGIVNE FYEQGDEEAT LGLPISPFMD
RSSPQLAKLQ ESFITHIVGP LCNSYDAAGL LPGQWIEAEE GDDTESDDDD DDDDDDDDDD
DEELDSDDEE TEDNLNPKPQ RRKGRRRIFC QLMHHLTENH KIWKEIIEEE EKCKAEGNKL
QVDNASLPQA DEIQVIEEAD EEEEQMFE
