PDE5_DICDI
ID PDE5_DICDI Reviewed; 867 AA.
AC Q8MLZ3; Q554K9;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=cGMP-dependent 3',5'-cGMP phosphodiesterase A;
DE EC=3.1.4.35 {ECO:0000269|PubMed:12429831, ECO:0000269|PubMed:12429832, ECO:0000305|PubMed:12198158};
DE AltName: Full=Cyclic GMP-binding protein A;
DE AltName: Full=Phosphodiesterase 5;
DE Short=DdPDE5;
DE AltName: Full=Phosphodiesterase D;
GN Name=pdeD; Synonyms=gbpA, pde5; ORFNames=DDB_G0274383;
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], FUNCTION, AND CATALYTIC ACTIVITY.
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, COFACTOR, AND DEVELOPMENTAL STAGE.
RX PubMed=12429831; DOI=10.1091/mbc.e02-05-0285;
RA Meima M.E., Biondi R.M., Schaap P.;
RT "Identification of a novel type of cGMP phosphodiesterase that is defective
RT in the chemotactic stmF mutants.";
RL Mol. Biol. Cell 13:3870-3877(2002).
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, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP 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 [6]
RP IDENTIFICATION.
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 [7]
RP BIOPHYSICOCHEMICAL PROPERTIES.
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 [8]
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: Phosphodiesterase specific for cGMP, which is activated by
CC cGMP but not by cAMP (PubMed:12429832, PubMed:12429831) (Probable).
CC Involved in the degradation of intracellular cGMP, contributes to the
CC control of cGMP signals (PubMed:12198158, PubMed:12429832).
CC {ECO:0000269|PubMed:12198158, ECO:0000269|PubMed:12429831,
CC ECO:0000269|PubMed:12429832, ECO:0000305|PubMed:12198158}.
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:12429831, ECO:0000269|PubMed:12429832,
CC ECO:0000305|PubMed:12198158};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958;
CC Evidence={ECO:0000269|PubMed:12429831, ECO:0000269|PubMed:12429832,
CC ECO:0000305|PubMed:12198158};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:12429831};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12429831};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12429831};
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:12429831};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.2 uM for cGMP {ECO:0000269|PubMed:12429832,
CC ECO:0000269|PubMed:12574165};
CC Vmax=390 pmol/min/mg enzyme {ECO:0000269|PubMed:12429832,
CC ECO:0000269|PubMed:12574165};
CC Note=cAMP/cGMP selectivity of 0.003.;
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:12429832,
CC ECO:0000269|PubMed:12574165};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12429831,
CC ECO:0000269|PubMed:12429832, ECO:0000269|PubMed:17040207}.
CC -!- DEVELOPMENTAL STAGE: Expressed during growth and development, with the
CC highest level of expression during aggregation.
CC {ECO:0000269|PubMed:12429831}.
CC -!- DOMAIN: The beta lactamase-like domain catalyzes the hydrolysis of
CC cGMP.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. cNMP
CC phosphodiesterase family. {ECO:0000305}.
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DR EMBL; AF481921; AAM34039.1; -; Genomic_DNA.
DR EMBL; AY047363; AAL06059.1; -; Genomic_DNA.
DR EMBL; AAFI02000012; EAL70084.1; -; Genomic_DNA.
DR RefSeq; XP_644314.1; XM_639222.1.
DR AlphaFoldDB; Q8MLZ3; -.
DR SMR; Q8MLZ3; -.
DR STRING; 44689.DDB0185054; -.
DR PaxDb; Q8MLZ3; -.
DR EnsemblProtists; EAL70084; EAL70084; DDB_G0274383.
DR GeneID; 8619742; -.
DR KEGG; ddi:DDB_G0274383; -.
DR dictyBase; DDB_G0274383; pdeD.
DR eggNOG; KOG1113; Eukaryota.
DR HOGENOM; CLU_010941_0_0_1; -.
DR InParanoid; Q8MLZ3; -.
DR OMA; HTIPCIG; -.
DR PhylomeDB; Q8MLZ3; -.
DR BRENDA; 3.1.4.35; 1939.
DR SABIO-RK; Q8MLZ3; -.
DR PRO; PR:Q8MLZ3; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IDA:dictyBase.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0046069; P:cGMP catabolic process; IDA:dictyBase.
DR GO; GO:0019934; P:cGMP-mediated signaling; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:dictyBase.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:dictyBase.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; IMP:dictyBase.
DR GO; GO:1905511; P:positive regulation of myosin II filament assembly; IMP:dictyBase.
DR GO; GO:0072697; P:protein localization to cell cortex; IGI:dictyBase.
DR GO; GO:0007165; P:signal transduction; 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; IPR018488; cNMP-bd_CS.
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; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
PE 1: Evidence at protein level;
KW cGMP; cGMP-binding; Cytoplasm; Hydrolase; Magnesium; Manganese;
KW Metal-binding; Nucleotide-binding; Reference proteome; Repeat; Zinc.
FT CHAIN 1..867
FT /note="cGMP-dependent 3',5'-cGMP phosphodiesterase A"
FT /id="PRO_0000353105"
FT REGION 121..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..503
FT /note="Phosphodiesterase activity"
FT COMPBIAS 121..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 399
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 401
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 403
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 607..721
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /ligand_label="1"
FT BINDING 734..851
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /ligand_label="2"
SQ SEQUENCE 867 AA; 97992 MW; E203EED614E6F386 CRC64;
MMFSKRKSIR FNPEGDYTEL PRGGYVVPSK LGGIQFGVPP ETIKDSMALK IDVPTIYVFP
EELWDRKTGI NAAEAEFPAY FNYFILKRKV SFVCTKEQEQ RIRIVFQETL LGPPEFNTGI
IINSSSSTTD TSKTSPIKKQ TSSSSPPLSP QQQQPPPPLV KQPSQQQLEE LATMDTCHYH
HHHHHQEVND NDNNNNTTTN NNNIEILEQQ QQQQQQQQQQ QDEDSTDVDE EFQKEFSSTF
PRSEIPNLEK ECKYLRTFNS VDELFDFILF DDNGIAKLSD DVEIHFQEDQ SLFKVLQFEE
TGKGNKVQTL VATIPSKILF PDMINSISTI NDNKIFDPPT FGITIIGSSH GFDPKKSTTG
FVLWINKRGI MVDPPLNSSS FLQSQGVPTR MVDHIILTHC HADHDSGTFQ KLLEEYQITV
VTTPTILGSF LRKYGALSNL STDLLRRLFI FRPVMIGEPM IISGAEFRFF YTIHTIPTIS
FEVFYGGKSI FYSGDTCYDP NRIKDMNKRG IMKTSRMKFF LRPWNHTVVL HEAGVPPIHT
PVSVLRALPD EVKNRLYLVH ISEHTLPAGS GLKIAKEGVA HTLSLDVMKS SHSEAVDILK
LVESVDIFRS IPLTQACEIL QTATKRKYSQ GSVIIARDTE PDAFYVVASG VVCVNIGELK
KNLIVGDYFG EMSLVMGGLR SANVQAVTDV EVLSFNKEDF LSITRNSTES IQFITRLWEM
RNEKSWETMS LNSVFSRCTN SQKTAIQSIL VRELIKKDET LWCKGEEALF GCLVAEGSFV
FKEDDSLESF SQGSFLGDIN AMTTQPPSIH KTTVVAKEES VIYKVLSQDL IKFFSNNPGI
QLAFLDTIFV DALRDQVQQL VNSKLTY
