PDE3A_RAT
ID PDE3A_RAT Reviewed; 1141 AA.
AC Q62865;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A {ECO:0000250|UniProtKB:Q14432};
DE EC=3.1.4.17 {ECO:0000250|UniProtKB:Q14432};
DE AltName: Full=Cyclic GMP-inhibited phosphodiesterase A;
DE Short=CGI-PDE A;
GN Name=Pde3a {ECO:0000312|RGD:61942};
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].
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).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Cyclic nucleotide phosphodiesterase with specificity for the
CC second messengers cAMP and cGMP, which are key regulators of many
CC important physiological processes. Has also activity toward cUMP.
CC Independently of its catalytic activity it is part of an E2/17beta-
CC estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the
CC PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of
CC SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease
CC activity. This apoptotic pathway might be relevant in tissues with high
CC concentration of E2 and be for instance involved in placenta
CC remodeling. {ECO:0000250|UniProtKB:Q14432}.
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:0000250|UniProtKB:Q14432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000250|UniProtKB:Q14432};
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:0000250|UniProtKB:Q14432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000250|UniProtKB:Q14432};
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:Q14432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000250|UniProtKB:Q14432};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic UMP + H2O = H(+) + UMP; Xref=Rhea:RHEA:70575,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57865,
CC ChEBI:CHEBI:184387; Evidence={ECO:0000250|UniProtKB:Q14432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70576;
CC Evidence={ECO:0000250|UniProtKB:Q14432};
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q14432};
CC Note=Binds 2 divalent metal cations per subunit.
CC {ECO:0000250|UniProtKB:Q14432};
CC -!- SUBUNIT: Homodimer. Interacts with PDE3A; direct low affinity
CC interaction which is stimulated by binding of 17beta-estradiol/E2 to
CC PDE3A and that positively regulates the ribonuclease activity of
CC SLFN12. {ECO:0000250|UniProtKB:Q14432}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9Z0X4}; Multi-
CC pass membrane protein {ECO:0000255}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q14432}.
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; U38179; AAA84964.1; -; mRNA.
DR RefSeq; NP_059033.1; NM_017337.1.
DR AlphaFoldDB; Q62865; -.
DR SMR; Q62865; -.
DR BioGRID; 248419; 2.
DR IntAct; Q62865; 1.
DR STRING; 10116.ENSRNOP00000032282; -.
DR PhosphoSitePlus; Q62865; -.
DR PaxDb; Q62865; -.
DR Ensembl; ENSRNOT00000032843; ENSRNOP00000032282; ENSRNOG00000025042.
DR GeneID; 50678; -.
DR KEGG; rno:50678; -.
DR UCSC; RGD:61942; rat.
DR CTD; 5139; -.
DR RGD; 61942; Pde3a.
DR eggNOG; ENOG502QSV8; Eukaryota.
DR GeneTree; ENSGT00940000156628; -.
DR HOGENOM; CLU_008844_0_0_1; -.
DR InParanoid; Q62865; -.
DR OMA; CRGCWGD; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q62865; -.
DR TreeFam; TF329631; -.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR SABIO-RK; Q62865; -.
DR PRO; PR:Q62865; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000025042; Expressed in heart and 17 other tissues.
DR Genevisible; Q62865; RN.
DR GO; GO:0005829; C:cytosol; IDA: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; ISO:RGD.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:Ensembl.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0004119; F:cGMP-inhibited cyclic-nucleotide phosphodiesterase activity; IEA:Ensembl.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; TAS:RGD.
DR GO; GO:0099130; F:estrogen binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISO:RGD.
DR GO; GO:0071321; P:cellular response to cGMP; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IMP:RGD.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:RGD.
DR GO; GO:0001556; P:oocyte maturation; IEP:RGD.
DR GO; GO:0060282; P:positive regulation of oocyte development; ISO:RGD.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:RGD.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; ISO:RGD.
DR GO; GO:0060700; P:regulation of ribonuclease activity; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; 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 cAMP; cGMP; Cytoplasm; Hydrolase; Isopeptide bond; Magnesium; Manganese;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..1141
FT /note="cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A"
FT /id="PRO_0000198801"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 674..1093
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 669..1141
FT /note="Interaction with SLFN12"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT REGION 1024..1062
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1098..1141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..448
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 533..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..636
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1031..1052
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1098..1115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1116..1135
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 752
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 752
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 756
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 836
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 837
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 837
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 837
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 950
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 950
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT BINDING 1001
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT MOD_RES 520
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X4"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X4"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X4"
FT MOD_RES 1036
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X4"
FT CROSSLNK 1120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q14432"
SQ SEQUENCE 1141 AA; 124301 MW; A333DFB44F6F33F3 CRC64;
MAVRGEAAQD WAKPGLRGPS PAPVARGDHR CRGGSPSSPR GSGCCWRALA LQPLRRSPQL
SSALCAGSLS VLLALLVRLV GGEVGGELES SQEAAAEEEE EEGARGGVFP GPRGGAPGGG
AQLSPWLQPA ALLFSLLCAF FWMGLCLLRA GVRLPLAVAL LAACCAGEAL VQLSLGVGDG
RLLSLPAAGV LLSCLGGATW LVLRLRLGVL MVALTSALRT VALVSLERFK VAWRPYLAYL
AAVLGLLLAR YAEQLLPQCS GPAPPRERFG SQSSARTKEE IPGWKRRRRS SSVVAGEMSG
CGGKSHRRTS LPCIPREQLM GHSEWDHKRG SRGSQSGTSV TVDIAVMGEA HGLITDLLAD
PSLPPNVCTS LRAVSNLLST QLTFQAIHKP RVNPTVTFSE NYTCSDSEEG LEKDKLAIPK
RLRRSLPPGL LRRVSSTWTT TTSATGLPTL EPAPVRRDRS ASIKPHEAPS PSAVNPDSWN
APVLMTLTKS RSFTSSYAVS AANHVKAKKQ NRPGGLDKIS PVPSPSSSPP QGSPTSSPVS
GIASVQFPES PEVTTKRGPG SHRALTYTQS APDLSPQIPP SPVICSSCGR PYSQGNPADG
PSERSGPAMQ KPNRTDDTSQ VTSDYETNNN SDSSDILQND EEAECQREPL RKASACGTYT
PQTMIFLDKP ILAPEPLVMD NLDSIMDQLN TWNFPIFDLV ENIGRKCGRI LSQVSYRLFE
DMGLFEAFKI PVREFMNYFH ALEIGYRDIP YHNRIHATDV LHAVWYLTTQ PIPGLPSVIG
DHGSASDSDS DSGFTHGHMG YVFSKAYHVP DDKYGCLSGN IPALELMALY VAAAMHDYDH
PGRTNAFLVA TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLVNLD HVEFKHFRFL
VIEAILATDL KKHFDFVAKF NAKVNDDVGI DWTNENDRLL VCQMCIKLAD INGPAKCKDL
HLRWTEGIAS EFYEQGDEEA SLGLPISPFM DRSAPQLANL QESFISHIVG PLCHSYDSAG
LMPGKWVDDS DDSGDTDDPE EEEEEAETPH EEETCENSEA PRKKSFKRRR IYCQITQHLL
QNHMMWKKVI EEEQCLSGTE NQAPDQAPLQ HSSEQIQAIK EEEEEKGKPR AEETLAPQPD
L
