PDE4A_DROME
ID PDE4A_DROME Reviewed; 1209 AA.
AC Q9W4T4;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase, isoform I;
DE EC=3.1.4.53;
DE AltName: Full=Learning/memory process protein;
DE AltName: Full=Protein dunce;
GN Name=dnc {ECO:0000312|EMBL:AAF45858.3}; ORFNames=CG32498;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000312|EMBL:AAF45858.3}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF45858.3}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-524.
RC STRAIN=Oregon-R;
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 495-1209, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBUNIT.
RC STRAIN=Canton-S {ECO:0000269|PubMed:1660926};
RX PubMed=1660926; DOI=10.1016/0022-2836(91)90496-s;
RA Qiu Y.H., Chen C.-N., Malone T., Richter L., Beckendorf S.K., Davis R.L.;
RT "Characterization of the memory gene dunce of Drosophila melanogaster.";
RL J. Mol. Biol. 222:553-565(1991).
CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key
CC regulator of many important physiological processes (By similarity).
CC Vital for female fertility. Required for learning/memory. {ECO:0000250,
CC ECO:0000269|PubMed:1660926}.
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:1660926};
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 -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:1660926}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=12;
CC Name=I {ECO:0000269|PubMed:1660926}; Synonyms=B
CC {ECO:0000303|PubMed:10731132}, S;
CC IsoId=Q9W4T4-1; Sequence=Displayed;
CC Name=II {ECO:0000269|PubMed:1660926}; Synonyms=I
CC {ECO:0000303|PubMed:10731132}, J {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-1; Sequence=External;
CC Name=III; Synonyms=E, P;
CC IsoId=P12252-7; Sequence=External;
CC Name=IV {ECO:0000269|PubMed:1660926}; Synonyms=A
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-3; Sequence=External;
CC Name=V {ECO:0000269|PubMed:1660926}; Synonyms=C
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-4; Sequence=External;
CC Name=VI {ECO:0000269|PubMed:1660926}; Synonyms=D
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-5; Sequence=External;
CC Name=VII {ECO:0000269|PubMed:1660926}; Synonyms=L
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-6; Sequence=External;
CC Name=F {ECO:0000303|PubMed:10731132};
CC IsoId=Q8IRU4-1; Sequence=External;
CC Name=G {ECO:0000303|PubMed:10731132};
CC IsoId=Q9W4S9-2; Sequence=External;
CC Name=N {ECO:0000303|PubMed:10731132};
CC IsoId=Q9W4S9-1; Sequence=External;
CC Name=R; Synonyms=Q;
CC IsoId=P12252-8, Q9W4T0-1;
CC Sequence=External;
CC Name=U; Synonyms=T;
CC IsoId=P12252-9; Sequence=External;
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA19668.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF45858.3; -; Genomic_DNA.
DR EMBL; AL024484; CAA19668.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_726846.1; NM_166959.2. [Q9W4T4-1]
DR RefSeq; NP_726847.2; NM_166960.3. [Q9W4T4-1]
DR AlphaFoldDB; Q9W4T4; -.
DR SMR; Q9W4T4; -.
DR BioGRID; 57834; 17.
DR IntAct; Q9W4T4; 1.
DR STRING; 7227.FBpp0305507; -.
DR PaxDb; Q9W4T4; -.
DR PRIDE; Q9W4T4; -.
DR DNASU; 31309; -.
DR EnsemblMetazoa; FBtr0070509; FBpp0070485; FBgn0000479. [Q9W4T4-1]
DR EnsemblMetazoa; FBtr0333315; FBpp0305507; FBgn0000479. [Q9W4T4-1]
DR GeneID; 31309; -.
DR UCSC; CG32498-RA; d. melanogaster. [Q9W4T4-1]
DR CTD; 31309; -.
DR FlyBase; FBgn0000479; dnc.
DR VEuPathDB; VectorBase:FBgn0000479; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000155190; -.
DR HOGENOM; CLU_007660_0_0_1; -.
DR InParanoid; Q9W4T4; -.
DR PhylomeDB; Q9W4T4; -.
DR Reactome; R-DME-180024; DARPP-32 events.
DR Reactome; R-DME-418555; G alpha (s) signalling events.
DR UniPathway; UPA00762; UER00747.
DR BioGRID-ORCS; 31309; 1 hit in 3 CRISPR screens.
DR ChiTaRS; dnc; fly.
DR GenomeRNAi; 31309; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0000479; Expressed in brain and 29 other tissues.
DR ExpressionAtlas; Q9W4T4; baseline and differential.
DR Genevisible; Q9W4T4; DM.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISS:FlyBase.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007615; P:anesthesia-resistant memory; IMP:FlyBase.
DR GO; GO:0008306; P:associative learning; IMP:FlyBase.
DR GO; GO:0048675; P:axon extension; IMP:FlyBase.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:FlyBase.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; TAS:FlyBase.
DR GO; GO:0001661; P:conditioned taste aversion; IMP:FlyBase.
DR GO; GO:0007619; P:courtship behavior; TAS:FlyBase.
DR GO; GO:0007612; P:learning; IMP:FlyBase.
DR GO; GO:0007617; P:mating behavior; TAS:FlyBase.
DR GO; GO:0072375; P:medium-term memory; IMP:FlyBase.
DR GO; GO:0007613; P:memory; IMP:FlyBase.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0046958; P:nonassociative learning; TAS:FlyBase.
DR GO; GO:0008355; P:olfactory learning; TAS:FlyBase.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; IMP:FlyBase.
DR GO; GO:0007614; P:short-term memory; IMP:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0040040; P:thermosensory behavior; IMP:FlyBase.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR040844; PDE4_UCR.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; cAMP; Hydrolase;
KW Metal-binding; Reference proteome.
FT CHAIN 1..1209
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase,
FT isoform I"
FT /id="PRO_0000198817"
FT DOMAIN 795..1124
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 16..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 59..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 754..792
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1146..1209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..342
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..649
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 754..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 775..790
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1163..1179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 871
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 871..875
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 875
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 911
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 912
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 912
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 912
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1029
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 1029
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1080
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT SITE 1032
FT /note="Binds AMP, but not cAMP"
FT /evidence="ECO:0000250"
FT CONFLICT 1097
FT /note="D -> S (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1166
FT /note="S -> T (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1181..1182
FT /note="SG -> R (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1209 AA; 129413 MW; A7E00D5BA862C1BE CRC64;
MMRLARFTQG FSFNKNVAKH RGSGSSNGTG NGSGTGNGQG LGGSCSANGL AATGGVGGGG
GSGSGGGGCG SGSGSGSGKR KSKARTKCFG GTVFRCCLPC RGGGSAAPAT SPPQTPAQTP
DELKVIPEDC NLEKSAEQKR DLLERNNKED DLLNRTVSGS ELDLYGGAGG GTKKHSLADT
IDTSVTTPIS LKTLINDVDE ELDQQLSAAD IAAASLASGL VARRAEPETL SDASVSPTAV
VQQQQQQQQQ LQQPLLQSQP HFVPSSGNIL SQVTLYSGSN PSTNPCQSAV QNQGQNSNPN
PNQNPNTNPN QNQQRCSCQP QTSPLPHIKE EEESDQANFK HQTSLKEHQP LPPPITIATG
YCGSCESVHH SSATSSSAGT VPPGGQQTQE YIAGTSSTPS PRIKLKFRKP HKSCWSRIVL
APIGSAGGSS SATTVIGSNS NETLASSSTT GGTATTTQNS SSVSVAAHHR LTSSSASALA
TSHPSNSQLL PTSKMQAEQG SIGDLQKYHS RYLKNRRHTL ANVRFDVENG QGARSPLEGG
SPSAGLVLQN LPQRRESFLY RSDSDFEMSP KSMSRNSSIA SERFKEQEAS ILVDRSHGED
LIVTPFAQIL ASLRSVRNNL LSLTNVPASN KSRRPNQSSS ASRSGNPPGA PLSQGEEAYT
RLATDTIEEL DWCLDQLETI QTHRSVSDMA SLKFKRMLNK ELSHFSESSR SGNQISEYIC
STFLDKQQEF DLPSLRVEDN PELVAANAAA GQQSAGQYAR SRSPRGPPMS QISGVKRPLS
HTNSFTGERL PTFGVETPRE NELGTLLGEL DTWGIQIFSI GEFSVNRPLT CVAYTIFQSR
ELLTSLMIPP KTFLNFMSTL EDHYVKDNPF HNSLHAADVT QSTNVLLNTP ALEGVFTPLE
VGGALFAACI HDVDHPGLTN QFLVNSSSEL ALMYNDESVL ENHHLAVAFK LLQNQGCDIF
CNMQKKQRQT LRKMVIDIVL STDMSKHMSL LADLKTMVET KKVAGSGVLL LDNYTDRIQV
LENLVHCADL SNPTKPLPLY KRWVALLMEE FFLQGDKERE SGMDISPMCD RHNATIEKSQ
VGFIDYIVHP LWETWADLVH PDAQDILDTL EENRDYYQSM IPPSPPPSGV DENPQEDRIR
FQVTLEESDQ ENLAELEEGD ESGGESTTTG TTGTTAASAL SGAGGGGGGG GGMAPRTGGC
QNQPQHGGM
