ID   PDE6_DICDI              Reviewed;        1096 AA.
AC   Q8MM62; Q552E1;
DT   25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 117.
DE   RecName: Full=cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase B;
DE            EC=3.1.4.35 {ECO:0000269|PubMed:12574165};
DE            EC=3.1.4.53 {ECO:0000269|PubMed:12574165};
DE   AltName: Full=Cyclic GMP-binding protein B;
DE   AltName: Full=Phosphodiesterase 6;
DE            Short=DdPDE6;
DE   AltName: Full=Phosphodiesterase E {ECO:0000303|PubMed:12574165};
DE            Short=PdeE {ECO:0000303|PubMed:12574165};
GN   Name=pdeE; Synonyms=gbpB, pde6; ORFNames=DDB_G0276027;
OS   Dictyostelium discoideum (Social amoeba).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=12011437; DOI=10.1073/pnas.102167299;
RA   Goldberg J.M., Bosgraaf L., Van Haastert P.J.M., Smith J.L.;
RT   "Identification of four candidate cGMP targets in Dictyostelium.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:6749-6754(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, DEVELOPMENTAL STAGE, AND COFACTOR.
RX   PubMed=12574165; DOI=10.1074/jbc.m209648200;
RA   Meima M.E., Weening K.E., Schaap P.;
RT   "Characterization of a cAMP-stimulated cAMP phosphodiesterase in
RT   Dictyostelium discoideum.";
RL   J. Biol. Chem. 278:14356-14362(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=12097910; DOI=10.1038/nature00847;
RA   Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA   Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA   Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA   Noegel A.A.;
RT   "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL   Nature 418:79-85(2002).
RN   [4]
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   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=12198158; DOI=10.1093/emboj/cdf438;
RA   Bosgraaf L., Russcher H., Smith J.L., Wessels D., Soll D.R.,
RA   Van Haastert P.J.M.;
RT   "A novel cGMP signalling pathway mediating myosin phosphorylation and
RT   chemotaxis in Dictyostelium.";
RL   EMBO J. 21:4560-4570(2002).
RN   [6]
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND DEVELOPMENTAL STAGE.
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   [7]
RP   SUBCELLULAR LOCATION.
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).
CC   -!- FUNCTION: Dual specificity cAMP and cGMP phosphodiesterase with marked
CC       preference for cyclic AMP, which is activated by cAMP and cGMP. Likely
CC       functions as a cAMP-stimulated cAMP-phosphodiesterase which may play a
CC       role in regulating the cAMP relay response.
CC       {ECO:0000269|PubMed:12198158, ECO:0000269|PubMed:12429832,
CC       ECO:0000269|PubMed:12574165}.
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         Evidence={ECO:0000269|PubMed:12574165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000269|PubMed:12574165};
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; EC=3.1.4.35;
CC         Evidence={ECO:0000269|PubMed:12574165};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:12574165};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:12574165};
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:12574165};
CC       Note=Divalent metal cation. Can use Mn(2+) or, to a lower extent,
CC       Mg(2+) or Zn(2+). Half-maximal activation occurs between 10 and 100 uM
CC       of Mn(2+) whereas maximal activation occurs with 10 mM of Zn(2+) or
CC       Mg(2+). {ECO:0000269|PubMed:12574165};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=200 uM for cAMP {ECO:0000269|PubMed:12198158,
CC         ECO:0000269|PubMed:12429832};
CC         KM=800 uM for cGMP {ECO:0000269|PubMed:12198158,
CC         ECO:0000269|PubMed:12429832};
CC         Vmax=650 nmol/min/mg enzyme with cAMP as substrate
CC         {ECO:0000269|PubMed:12198158, ECO:0000269|PubMed:12429832};
CC         Vmax=300 nmol/min/mg enzyme with cGMP as substrate
CC         {ECO:0000269|PubMed:12198158, ECO:0000269|PubMed:12429832};
CC         Note=cAMP/cGMP selectivity of 9.;
CC       pH dependence:
CC         Optimum pH is 7.0. {ECO:0000269|PubMed:12198158,
CC         ECO:0000269|PubMed:12429832, ECO:0000269|PubMed:12574165};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:12198158,
CC       ECO:0000305|PubMed:17040207}.
CC   -!- DEVELOPMENTAL STAGE: Low expression during growth. Mainly expressed
CC       after 8-10 hours of starvation when cells are aggregating and in the
CC       multicellular stage. {ECO:0000269|PubMed:12198158,
CC       ECO:0000269|PubMed:12429832, ECO:0000269|PubMed:12574165}.
CC   -!- DOMAIN: The beta lactamase-like domain catalyzes the hydrolysis of
CC       cGMP. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. cNMP
CC       phosphodiesterase family. {ECO:0000305}.
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DR   EMBL; AF481922; AAM34040.1; -; Genomic_DNA.
DR   EMBL; AY047364; AAL06060.1; -; Genomic_DNA.
DR   EMBL; AAFI02000014; EAL69313.1; -; Genomic_DNA.
DR   RefSeq; XP_643272.1; XM_638180.1.
DR   AlphaFoldDB; Q8MM62; -.
DR   SMR; Q8MM62; -.
DR   STRING; 44689.Q8MM62; -.
DR   PaxDb; 44689-DDB0185220; -.
DR   EnsemblProtists; EAL69313; EAL69313; DDB_G0276027.
DR   GeneID; 8620315; -.
DR   KEGG; ddi:DDB_G0276027; -.
DR   dictyBase; DDB_G0276027; pdeE.
DR   eggNOG; ENOG502R2P1; Eukaryota.
DR   HOGENOM; CLU_283926_0_0_1; -.
DR   InParanoid; Q8MM62; -.
DR   OMA; MIIHESG; -.
DR   SABIO-RK; Q8MM62; -.
DR   PRO; PR:Q8MM62; -.
DR   Proteomes; UP000002195; Chromosome 2.
DR   GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:dictyBase.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:dictyBase.
DR   GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IMP:dictyBase.
DR   GO; GO:0019933; P:cAMP-mediated signaling; IDA:dictyBase.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IMP:dictyBase.
DR   GO; GO:0072697; P:protein localization to cell cortex; IGI:dictyBase.
DR   GO; GO:0061120; P:regulation of positive chemotaxis to cAMP by DIF-1; IMP:dictyBase.
DR   CDD; cd00038; CAP_ED; 2.
DR   CDD; cd07738; DdPDE5-like_MBL-fold; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 2.
DR   Gene3D; 3.60.15.10; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   PANTHER; PTHR11635; CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN; 1.
DR   PANTHER; PTHR11635:SF165; CAMP_CGMP-DEPENDENT 3',5'-CAMP_CGMP PHOSPHODIESTERASE B; 1.
DR   Pfam; PF00027; cNMP_binding; 2.
DR   Pfam; PF00753; Lactamase_B; 1.
DR   SMART; SM00100; cNMP; 2.
DR   SMART; SM00849; Lactamase_B; 1.
DR   SUPFAM; SSF51206; cAMP-binding domain-like; 2.
DR   SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 2.
PE   1: Evidence at protein level;
KW   cAMP; cAMP-binding; cGMP; cGMP-binding; Cytoplasm; Hydrolase; Magnesium;
KW   Manganese; Metal-binding; Nucleotide-binding; Reference proteome; Repeat;
KW   Zinc.
FT   CHAIN           1..1096
FT                   /note="cAMP/cGMP-dependent 3',5'-cAMP/cGMP
FT                   phosphodiesterase B"
FT                   /id="PRO_0000353106"
FT   REGION          216..248
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         573
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         575
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         577
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         783..930
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /ligand_label="1"
FT   BINDING         946..1070
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /ligand_label="2"
SQ   SEQUENCE   1096 AA;  124924 MW;  4F4F8CF199223782 CRC64;
     MNSKYGDNII DFLRYLEKFV KSLTKDNKIE EFKTFDIKSL LYPRNKDYFG NLSKFLLAVI
     SARIGSNFIN EDDIFEISEL LKEFLGQELE HLPYLSYEEL YVEIVEQVGE INGTVSEIIE
     AITVTIDFLD TFEKVSQTID RSNEKQKLLA YLSAPVNQLD NSVSGVFNEN DYTDIQRFFT
     ELTNENNQSP DSNISILIND FQSLLNILES QQASSSSSKM IINDSPRTQQ RNGTTEQQKK
     QQQQQYLQKN KEPFYSKDKI MQVSGPSYVF TPSDCNVSIQ VGIPPDTLKR DQSICHFIVP
     HFLISKDVSL SEVEFPIFYN KFVQKGKTKV VIICTVEQKQ RIETILCESI FGPAPEHIYT
     DEEITIPDYK IDLLTERLAI DPRANDEKLD SYVIFKTFDT FGVVDIDLPS ASDPTKLINL
     RIRNTKGLIS FHEDYHVVQK QLHLKLQEQQ QDQQDKSSSS TTDKQMINTS GNRIILKNNT
     VSVIDSTIES QYVPVLPFGN DHEQVKKFKA PILGVTFLGV SHGLDFTHCS HTTGFIIWIN
     GSGVVVDPPV GNTTYLQTNG IYGKTVEHII LTHCHADHDS GILQKIIERN KVTLYTTKTI
     NESYMRKLKA LTGLPEQSLK NYYTWVPVTI GNKIKILGAE FEFDYSFHVI PTIRFKLEIY
     NKKISYSADT FYDLQKFKQL KDQGVLSKKR IERLKSFVFD ADMIIHESGV APIHTPMANL
     LELPSEIRKK IRVVHCSSSV DTKGEIIRPK EGLENTEIIK VDRKYKGVAE CIQIQTALNH
     CSVFSKLSPA EVQRVFFLCK KIWVKRNDVI IKKGSPSDMF YIILSGKVLV YENEYEPIKS
     TTSVGTVVTD TTTITTTVKT DAIKIPTIKL CAGETLGESA LQLDKNIDAS ATVIAETDVC
     LLVWKTMDLR TEFHSNLNTF ISKVHMDLSH INSCRDAIIR AFQHNITQHI NKEEVDSIAN
     GSKDVSFAHH QVIFNEGDTS DSMYIIKQGR VRIHSKKNKN IIRYLNVGDF FGETAYRRSN
     EDSNFLPTRS FTATAIDPTI LLKLDIESIV NPRIQNIIEQ KAKKNAEDNI RYHAYSPKIR
     TPRTPRKVYP IEGLSI
//