PDE3A_MOUSE
ID PDE3A_MOUSE Reviewed; 1141 AA.
AC Q9Z0X4;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A {ECO:0000305|PubMed:11420239};
DE EC=3.1.4.17 {ECO:0000269|PubMed:11420239};
DE AltName: Full=Cyclic GMP-inhibited phosphodiesterase A;
DE Short=CGI-PDE A;
GN Name=Pde3a {ECO:0000312|MGI:MGI:1860764};
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,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J; TISSUE=Ovary;
RX PubMed=11420239; DOI=10.1095/biolreprod65.1.188;
RA Shitsukawa K., Andersen C.B., Richard F.J., Horner A.K., Wiersma A.,
RA van Duin M., Conti M.;
RT "Cloning and characterization of the cyclic guanosine monophosphate-
RT inhibited phosphodiesterase PDE3A expressed in mouse oocyte.";
RL Biol. Reprod. 65:188-196(2001).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492; SER-520; SER-524;
RP SER-533; SER-1033 AND THR-1036, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
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 specificity for the
CC second messengers cAMP and cGMP, which are key regulators of many
CC important physiological processes (PubMed:11420239). Has also activity
CC toward cUMP (By similarity). Independently of its catalytic activity it
CC is part of an E2/17beta-estradiol-induced pro-apoptotic signaling
CC pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol,
CC promoting the dephosphorylation of SLFN12 and activating its pro-
CC apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic
CC pathway might be relevant in tissues with high concentration of E2 and
CC be for instance involved in placenta remodeling (By similarity).
CC {ECO:0000250|UniProtKB:Q14432, ECO:0000269|PubMed:11420239}.
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:11420239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14654;
CC Evidence={ECO:0000305|PubMed:11420239};
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:11420239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:11420239};
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 -!- ACTIVITY REGULATION: Inhibited by cGMP. {ECO:0000250|UniProtKB:Q14432}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.2 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:11420239};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11420239}; 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}.
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DR EMBL; AF099187; AAD16300.1; -; mRNA.
DR CCDS; CCDS20676.1; -.
DR RefSeq; NP_061249.1; NM_018779.1.
DR AlphaFoldDB; Q9Z0X4; -.
DR SMR; Q9Z0X4; -.
DR BioGRID; 207686; 4.
DR IntAct; Q9Z0X4; 2.
DR MINT; Q9Z0X4; -.
DR STRING; 10090.ENSMUSP00000038749; -.
DR iPTMnet; Q9Z0X4; -.
DR PhosphoSitePlus; Q9Z0X4; -.
DR jPOST; Q9Z0X4; -.
DR MaxQB; Q9Z0X4; -.
DR PaxDb; Q9Z0X4; -.
DR PRIDE; Q9Z0X4; -.
DR ProteomicsDB; 301779; -.
DR Antibodypedia; 2869; 232 antibodies from 32 providers.
DR DNASU; 54611; -.
DR Ensembl; ENSMUST00000043259; ENSMUSP00000038749; ENSMUSG00000041741.
DR GeneID; 54611; -.
DR KEGG; mmu:54611; -.
DR UCSC; uc009eon.1; mouse.
DR CTD; 5139; -.
DR MGI; MGI:1860764; Pde3a.
DR VEuPathDB; HostDB:ENSMUSG00000041741; -.
DR eggNOG; ENOG502QSV8; Eukaryota.
DR GeneTree; ENSGT00940000156628; -.
DR HOGENOM; CLU_008844_0_0_1; -.
DR InParanoid; Q9Z0X4; -.
DR OMA; CRGCWGD; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q9Z0X4; -.
DR TreeFam; TF329631; -.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR SABIO-RK; Q9Z0X4; -.
DR BioGRID-ORCS; 54611; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Pde3a; mouse.
DR PRO; PR:Q9Z0X4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9Z0X4; protein.
DR Bgee; ENSMUSG00000041741; Expressed in secondary oocyte and 119 other tissues.
DR ExpressionAtlas; Q9Z0X4; baseline and differential.
DR Genevisible; Q9Z0X4; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:MGI.
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:0004119; F:cGMP-inhibited cyclic-nucleotide phosphodiesterase activity; ISO:MGI.
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:MGI.
DR GO; GO:0071321; P:cellular response to cGMP; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:MGI.
DR GO; GO:0048599; P:oocyte development; IGI:MGI.
DR GO; GO:0001556; P:oocyte maturation; IDA:MGI.
DR GO; GO:0060282; P:positive regulation of oocyte development; IGI:MGI.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:MGI.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IDA:MGI.
DR GO; GO:0060700; P:regulation of ribonuclease activity; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; 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 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_0000198800"
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..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..654
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..1060
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1120..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 612..636
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1031..1051
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1120..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:0007744|PubMed:21183079"
FT MOD_RES 520
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1036
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
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; 124513 MW; 3D9ACCFF928219D8 CRC64;
MAVRGEAAQD LAKPGLGGAS PARVARGNHR HRGESSPSPR GSGCCWRALA LQPLRRSPQL
SSALCAGSLS VLLALLVRLV GGEVGGELEK SQEAAAEEEE EEGARGGVFP GPRGGAPGGG
AQLSPWLQPA ALLFSLLCAF FWMGLCLLRA GVRLPLAVAL LAACCAGEAL VQLSLGVGDG
RLLSLPAAGV LLSCLGGATW LVLRLRLGVL MVAWTSVLRT VALVSLERFK VAWRPYLAYL
AAVLGLLLAR YAEQILPQCS GPAPPRERFG SQLSARTKEE IPGWKRRRRS SSVVAGEMSG
CSGKSHRRTS LPCIPREQLM GHSEWDHKRG PRGSQSGTSI TVDIAVMGEA HGLITDLLAD
PSLPPNVCTS LRAVSNLLST QLTFQAIHKP RVNPTVTFSE NYTCSDSEEG LEKDKQAISK
RLRRSLPPGL LRRVSSTWTT TTSATGLPTL EPAPVRRDRS ASIKPHEAPS PSAVNPDSWN
APGLTTLTKS RSFTSSYAVS AANHVKAKKQ NRPGGLAKIS PVPSPSSSPP QGSPASSPVS
NSASQQFPES PEVTIKRGPG SHRALTYTQS APDLSPQIPP PSVICSSCGR PYSQGNPADG
PSERSGPAML KPNRTDDTSQ VTSDYETNNN SDSSDILQNE EEAECQREPQ RKASACGTYT
SQTMIFLDKP ILAPEPLVMD NLDSIMDQLN TWNFPIFDLM ENIGRKCGRI LSQVSYRLFE
DMGLFEAFKI PVREFMNYFH ALEIGYRDIP YHNRIHATDV LHAVWYLTTQ PIPGLPSVIG
DHGSASDSDS DSGFTHGHMG YVFSKMYHVP DDKYGCLSGN IPALELMALY VAAAMHDYDH
PGRTNAFLVA TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLVNLD HVEFKHFRFL
VIEAILATDL KKHFDFVAKF NAKVNDDVGI DWTNENDRLL VCQMCIKLAD INGPAKCKEL
HLRWTEGIAS EFYEQGDEEA SLGLPISPFM DRSAPQLANL QESFISHIVG PLCHSYDSAG
LMPGKWVDDS DDSGDTDDPE EEEEEAETPH EDEACESSIA PRKKSFKRRR IYCQITQHLL
QNHMMWKKVI EEEQCLSGTE NQSLDQVPLQ HPSEQIQAIK EEEEEKGKPR AEETLAPQPD
L
