PDE6_DICDI
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 03-AUG-2022, entry version 110.
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 (Slime mold).
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.DDB0185220; -.
DR PaxDb; Q8MM62; -.
DR PRIDE; Q8MM62; -.
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:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IBA:GO_Central.
DR GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0006198; P:cAMP catabolic process; IDA:dictyBase.
DR GO; GO:0019934; P:cGMP-mediated signaling; IMP:dictyBase.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IBA:GO_Central.
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 Gene3D; 2.60.120.10; -; 2.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR014710; RmlC-like_jellyroll.
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; SSF51206; 2.
DR SUPFAM; SSF56281; SSF56281; 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
