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   07-JUL-2009, entry version 61.
DE   RecName: Full=3',5'-cyclic-nucleotide phosphodiesterase regA;
DE            Short=PDEase regA;
DE            EC=3.1.4.53;
DE   AltName: Full=Response regulator protein A;
DE   AltName: Full=cAMP-specific 3',5'-cAMP phosphodiesterase 2;
DE   AltName: Full=Phosphodiesterase 2;
DE            Short=DdPDE2;
GN   Name=regA; Synonyms=pde2; ORFNames=DDB_G0284331;
OS   Dictyostelium discoideum (Slime mold).
OC   Eukaryota; Amoebozoa; Mycetozoa; Dictyosteliida; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RC   STRAIN=AX4;
RX   MEDLINE=97140317; 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], ENZYME REGULATION, AND MUTAGENESIS
RP   OF 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.,
RA   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.,
RA   Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q.,
RA   Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F.,
RA   Bankier A.T., Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P.,
RA   Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P.,
RA   Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N.,
RA   Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M.,
RA   Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I.,
RA   Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R.,
RA   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.,
RA   Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D.,
RA   Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S.,
RA   Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T.,
RA   Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A.,
RA   Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M.,
RA   Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G.,
RA   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;
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   ENZYME 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   MEDLINE=20431894; PubMed=10974109;
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   phoshodiesterases in dictyostelium.";
RL   Mol. Biol. Cell 13:3878-3889(2002).
RN   [9]
RP   SUBCELLULAR LOCATION, AND ENZYME 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
RT   of 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
RT   Dictyostelium.";
RL   Genome Biol. 8:RESEARCH144.1-RESEARCH144.15(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.,
RA   Peracino B., Skelton J., Ivens A., Bozzaro S.;
RT   "Genome-wide transcriptional changes induced by phagocytosis or growth
RT   on 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
CC       tagB. Phosphorelay protein that accepts phosphate from rdeA or
CC       supplies phosphate from regA; depending on the relative
CC       concentration of the phosphodonor proteins.
CC   -!- CATALYTIC ACTIVITY: Adenosine 3',5'-cyclic phosphate + H(2)O =
CC       adenosine 5'-phosphate.
CC   -!- ENZYME REGULATION: Inhibited by 3-isobutyl-1-methylxanthine
CC       (IBMX).
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5 uM for cAMP;
CC         Vmax=50 pmol/min/mg enzyme with cAMP as substrate;
CC         Note=cAMP/cGMP selectivity of 200;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC   -!- DEVELOPMENTAL STAGE: Expressed at low levels in vegetative cells
CC       and at high levels in prespore and prestalk cells during
CC       development. Developmentally regulated. Not observable before the
CC       end of aggregation, peaks at the mound stage and remains at a
CC       lower level thereafter.
CC   -!- INDUCTION: Down-regulated by phagocytic stimuli.
CC   -!- PTM: The phosphorelay mechanism involves the sequential transfer
CC       of a phosphate group from Asp-212 of pde2 to 'His-65' of rdeA.
CC       Phosphorylation of Asp-212 activates the phosphodiesterase domain.
CC   -!- DISRUPTION PHENOTYPE: Rapid development. Cells are 4-fold more
CC       resistant to the antitumor agent cisplatin than are wild-type
CC       cells. Additionally it produces fruiting bodies with spore masses
CC       that cannot rise up the stalk during development. Mutant cells
CC       grow exponentially at the same rate as wild-type. Disruption of
CC       regA in a tagB null or in a tagC null background resulted in
CC       higher levels of sporulation. Disruption of regA in a dhka null
CC       background corrects the defect in stalk formation and suppresses
CC       the block to sporulation.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase
CC       family.
CC   -!- SIMILARITY: Contains 1 response regulatory domain.
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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; -.
DR   HSSP; P06143; 1JBE.
DR   GeneID; 3390184; -.
DR   KEGG; ddi:DDB_0191479; -.
DR   dictyBase; DDB_G0284331; regA.
DR   BRENDA; 3.1.4.17; 424.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase a...; IEA:InterPro.
DR   GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0000156; F:two-component response regulator activity; IEA:InterPro.
DR   GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:InterPro.
DR   GO; GO:0000160; P:two-component signal transduction system (p...; IEA:InterPro.
DR   InterPro; IPR003607; Met-dep_phosphohydro_HD.
DR   InterPro; IPR002073; PDEase.
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   ProDom; PD000039; Response_reg; 1.
DR   SMART; SM00471; HDc; 1.
DR   SMART; SM00448; REC; 1.
DR   PROSITE; PS00126; PDEASE_I; 1.
DR   PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE   1: Evidence at protein level;
KW   cAMP; cAMP-binding; Complete proteome; Cytoplasm; Hydrolase;
KW   Nucleotide-binding; Phosphoprotein.
FT   CHAIN         1    793       3',5'-cyclic-nucleotide phosphodiesterase
FT                                regA.
FT                                /FTId=PRO_0000198850.
FT   DOMAIN      161    280       Response regulatory.
FT   COMPBIAS     18     28       Poly-Ser.
FT   COMPBIAS     52     69       Poly-Asn.
FT   COMPBIAS     87     96       Poly-Thr.
FT   COMPBIAS    100    121       Poly-Asn.
FT   COMPBIAS    166    169       Poly-Asp.
FT   COMPBIAS    770    776       Poly-Ser.
FT   MOD_RES     212    212       4-aspartylphosphate (By similarity).
FT   MUTAGEN     212    212       D->N: Loss of phosphorylation and
FT                                activation.
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
//