PDE2_DICDI
ID PDE2_DICDI Reviewed; 793 AA.
AC Q23917; Q54PP2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=3',5'-cyclic-nucleotide phosphodiesterase regA;
DE Short=PDEase regA;
DE EC=3.1.4.53;
DE AltName: Full=Phosphodiesterase 2;
DE Short=DdPDE2;
DE AltName: Full=Response regulator protein A;
DE AltName: Full=cAMP-specific 3',5'-cAMP phosphodiesterase 2;
GN Name=regA; Synonyms=pde2; ORFNames=DDB_G0284331;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RC STRAIN=AX4;
RX PubMed=8986798; DOI=10.1073/pnas.93.26.15260;
RA Shaulsky G., Escalante R., Loomis W.F.;
RT "Developmental signal transduction pathways uncovered by genetic
RT suppressors.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:15260-15265(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ASP-212.
RC STRAIN=AX2;
RX PubMed=9582277; DOI=10.1093/emboj/17.10.2838;
RA Thomason P.A., Traynor D., Cavet G., Chang W.-T., Harwood A.J., Kay R.R.;
RT "An intersection of the cAMP/PKA and two-component signal transduction
RT systems in Dictyostelium.";
RL EMBO J. 17:2838-2845(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=9191038; DOI=10.1242/jcs.110.10.1141;
RA Loomis W.F., Shaulsky G., Wang N.;
RT "Histidine kinases in signal transduction pathways of eukaryotes.";
RL J. Cell Sci. 110:1141-1145(1997).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=9812977; DOI=10.1074/jbc.273.47.30859;
RA Kim H.-J., Chang W.-T., Meima M., Gross J.D., Schaap P.;
RT "A novel adenylyl cyclase detected in rapidly developing mutants of
RT Dictyostelium.";
RL J. Biol. Chem. 273:30859-30862(1998).
RN [6]
RP ACTIVITY REGULATION, FUNCTION, PHOSPHORYLATION, AND DEVELOPMENTAL STAGE.
RX PubMed=10488068; DOI=10.1074/jbc.274.39.27379;
RA Thomason P.A., Traynor D., Stock J.B., Kay R.R.;
RT "The RdeA-RegA system, a eukaryotic phospho-relay controlling cAMP
RT breakdown.";
RL J. Biol. Chem. 274:27379-27384(1999).
RN [7]
RP DISRUPTION PHENOTYPE.
RC STRAIN=AX4;
RX PubMed=10974109; DOI=10.1099/00221287-146-9-2219;
RA Li G., Alexander H., Schneider N., Alexander S.;
RT "Molecular basis for resistance to the anticancer drug cisplatin in
RT Dictyostelium.";
RL Microbiology 146:2219-2227(2000).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12429832; DOI=10.1091/mbc.e02-05-0302;
RA Bosgraaf L., Russcher H., Snippe H., Bader S., Wind J.,
RA Van Haastert P.J.M.;
RT "Identification and characterization of two unusual cGMP-stimulated
RT phosphodiesterases in dictyostelium.";
RL Mol. Biol. Cell 13:3878-3889(2002).
RN [9]
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=17040207; DOI=10.1042/bj20061153;
RA Bader S., Kortholt A., Van Haastert P.J.M.;
RT "Seven Dictyostelium discoideum phosphodiesterases degrade three pools of
RT cAMP and cGMP.";
RL Biochem. J. 402:153-161(2007).
RN [10]
RP IDENTIFICATION.
RX PubMed=17659086; DOI=10.1186/gb-2007-8-7-r144;
RA Sawai S., Guan X.-J., Kuspa A., Cox E.C.;
RT "High-throughput analysis of spatio-temporal dynamics in Dictyostelium.";
RL Genome Biol. 8:R144.1-R144.15(2007).
RN [11]
RP INDUCTION [LARGE SCALE ANALYSIS].
RX PubMed=18559084; DOI=10.1186/1471-2164-9-291;
RA Sillo A., Bloomfield G., Balest A., Balbo A., Pergolizzi B., Peracino B.,
RA Skelton J., Ivens A., Bozzaro S.;
RT "Genome-wide transcriptional changes induced by phagocytosis or growth on
RT bacteria in Dictyostelium.";
RL BMC Genomics 9:291-291(2008).
CC -!- FUNCTION: Phosphodiesterase specific for cAMP. Involved in the
CC degradation of intracellular cAMP. Morphological suppressor of tagB.
CC Phosphorelay protein that accepts phosphate from rdeA or supplies
CC phosphate from regA; depending on the relative concentration of the
CC phosphodonor proteins. {ECO:0000269|PubMed:10488068,
CC ECO:0000269|PubMed:12429832}.
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; EC=3.1.4.53;
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions, while site 2 has a preference for
CC magnesium and/or manganese ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by 3-isobutyl-1-methylxanthine (IBMX).
CC {ECO:0000269|PubMed:10488068, ECO:0000269|PubMed:17040207,
CC ECO:0000269|PubMed:9582277}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for cAMP {ECO:0000269|PubMed:12429832};
CC Vmax=50 pmol/min/mg enzyme with cAMP as substrate
CC {ECO:0000269|PubMed:12429832};
CC Note=cAMP/cGMP selectivity of 200.;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12429832,
CC ECO:0000269|PubMed:17040207}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low levels in vegetative cells and at
CC high levels in prespore and prestalk cells during development.
CC Developmentally regulated. Not observable before the end of
CC aggregation, peaks at the mound stage and remains at a lower level
CC thereafter. {ECO:0000269|PubMed:10488068}.
CC -!- INDUCTION: Down-regulated by phagocytic stimuli.
CC {ECO:0000269|PubMed:18559084}.
CC -!- PTM: The phosphorelay mechanism involves the sequential transfer of a
CC phosphate group from Asp-212 of pde2 to 'His-65' of rdeA.
CC Phosphorylation of Asp-212 activates the phosphodiesterase domain.
CC {ECO:0000269|PubMed:10488068}.
CC -!- DISRUPTION PHENOTYPE: Rapid development. Cells are 4-fold more
CC resistant to the antitumor agent cisplatin than are wild-type cells.
CC Additionally it produces fruiting bodies with spore masses that cannot
CC rise up the stalk during development. Mutant cells grow exponentially
CC at the same rate as wild-type. Disruption of regA in a tagB null or in
CC a tagC null background resulted in higher levels of sporulation.
CC Disruption of regA in a dhka null background corrects the defect in
CC stalk formation and suppresses the block to sporulation.
CC {ECO:0000269|PubMed:10974109, ECO:0000269|PubMed:8986798,
CC ECO:0000269|PubMed:9191038, ECO:0000269|PubMed:9812977}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
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DR EMBL; U60170; AAB03508.1; -; Genomic_DNA.
DR EMBL; AJ005398; CAA06513.1; -; Genomic_DNA.
DR EMBL; AAFI02000064; EAL65213.1; -; Genomic_DNA.
DR RefSeq; XP_638612.1; XM_633520.1.
DR AlphaFoldDB; Q23917; -.
DR SMR; Q23917; -.
DR STRING; 44689.DDB0191479; -.
DR PaxDb; Q23917; -.
DR EnsemblProtists; EAL65213; EAL65213; DDB_G0284331.
DR GeneID; 8624583; -.
DR KEGG; ddi:DDB_G0284331; -.
DR dictyBase; DDB_G0284331; regA.
DR eggNOG; KOG1601; Eukaryota.
DR eggNOG; KOG3689; Eukaryota.
DR HOGENOM; CLU_354286_0_0_1; -.
DR InParanoid; Q23917; -.
DR OMA; KEDRQMI; -.
DR PhylomeDB; Q23917; -.
DR BRENDA; 3.1.4.53; 1939.
DR Reactome; R-DDI-111957; Cam-PDE 1 activation.
DR Reactome; R-DDI-165160; PDE3B signalling.
DR Reactome; R-DDI-418457; cGMP effects.
DR Reactome; R-DDI-418555; G alpha (s) signalling events.
DR SABIO-RK; Q23917; -.
DR PRO; PR:Q23917; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005829; C:cytosol; TAS:dictyBase.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:dictyBase.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IDA:dictyBase.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000156; F:phosphorelay response regulator activity; IMP:dictyBase.
DR GO; GO:0046058; P:cAMP metabolic process; IMP:dictyBase.
DR GO; GO:0120320; P:lateral pseudopodium retraction; IMP:dictyBase.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IMP:dictyBase.
DR GO; GO:0061128; P:positive regulation of chemotaxis to cAMP by DIF-2; IMP:dictyBase.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:dictyBase.
DR GO; GO:1904776; P:regulation of protein localization to cell cortex; IMP:dictyBase.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IMP:dictyBase.
DR GO; GO:0006970; P:response to osmotic stress; TAS:dictyBase.
DR GO; GO:0010225; P:response to UV-C; IDA:dictyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
DR GO; GO:0031288; P:sorocarp morphogenesis; IMP:dictyBase.
DR GO; GO:0048837; P:sorocarp sorus development; IMP:dictyBase.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:dictyBase.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR Pfam; PF00233; PDEase_I; 1.
DR Pfam; PF00072; Response_reg; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR SMART; SM00448; REC; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW cAMP; cAMP-binding; Cytoplasm; Hydrolase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..793
FT /note="3',5'-cyclic-nucleotide phosphodiesterase regA"
FT /id="PRO_0000198850"
FT DOMAIN 161..280
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DOMAIN 410..733
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 756..793
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 770..793
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 487
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 491
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 527
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 528
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 528
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 639
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 212
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT MUTAGEN 212
FT /note="D->N: Loss of phosphorylation and activation."
FT /evidence="ECO:0000269|PubMed:9582277"
SQ SEQUENCE 793 AA; 91176 MW; 6E065A96620F8C27 CRC64;
MNNKQEEIDQ FLSSTSTSPS PSSSSSPSNN DSTSLKSMIS GIENLNVHSK GNDNKNNNNN
NNNNNSNNNE KQKDIVSLEN NSSSNNTTTT TTTTTTSNHN SNNNSNNNNN NINNNNINNN
NYEPLVNGHN NGFGDKLNDQ PSPSSHRVSD FSDEYSPSKV RILVADDDDV QRKILNNLLK
KFHYNVTLVP NGEIAWEYIN KGQQKYDLVL TDVMMPHITG FDLLQRINDH PVHRHIPVIL
MSGTAVDYKY ANDTIKIGGQ DFLTKPIAKE LLKKKIDTVL QSIWQRRKEE EYKATLAQER
EKGNKLAKEM ELKEHEIEEL TKKVSKMSSI SKEAMESPLV SVTRNIEELL KQSSWSHYES
EIKEKLSSIL KELGSSNIYR PSFEKLIKND SVDPVTKSFL VSEFSSTTSR RNSIPTFPQT
TYNRDTKEVI KGWEFDVFKY SEDDLMPLLV DMFENFQLPE IFKIPIEKLQ RFIMTVNALY
RKNNRYHNFT HAFDVTQTVY TFLTSFNAAQ YLTHLDIFAL LISCMCHDLN HPGFNNTFQV
NAQTELSLEY NDISVLENHH AMLTFKILRN SECNILEGLN EDQYKELRRS VVQLILATDM
QNHFEHTNKF QHHLNNLPFD RNKKEDRQMI LNFLIKCGDI SNIARPWHLN FEWSLRVSDE
FFQQSHYETI CGYPVTPFMD KTKTTRARIA ADFIDFVASP LFQSMAKFLK ESQFLLKVIS
KNRENWQAYM ELQKEGKCND DDLQFMEDPT ILVKSKLPKI DEEENRDKVS SSSSSSTAPL
TSTSSSNNET SSS
