PDE4E_DROME
ID PDE4E_DROME Reviewed; 662 AA.
AC Q8IRU4;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase, isoform F;
DE EC=3.1.4.53;
DE AltName: Full=Learning/memory process protein;
DE AltName: Full=Protein dunce;
GN Name=dnc {ECO:0000312|EMBL:AAN09606.1}; 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:AAN09606.1}
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:AAN09606.1}
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).
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 (By
CC similarity). {ECO:0000250}.
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:0000250|UniProtKB:P12252};
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:0000250|UniProtKB:P12252}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=12;
CC Name=F {ECO:0000303|PubMed:10731132};
CC IsoId=Q8IRU4-1; Sequence=Displayed;
CC Name=G {ECO:0000303|PubMed:10731132};
CC IsoId=Q9W4S9-2; Sequence=External;
CC Name=I {ECO:0000250|UniProtKB:P12252}; Synonyms=B
CC {ECO:0000303|PubMed:10731132}, S;
CC IsoId=Q9W4T4-1; Sequence=External;
CC Name=II {ECO:0000250|UniProtKB:P12252}; 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:0000250|UniProtKB:P12252}; Synonyms=A
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-3; Sequence=External;
CC Name=V {ECO:0000250|UniProtKB:P12252}; Synonyms=C
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-4; Sequence=External;
CC Name=VI {ECO:0000250|UniProtKB:P12252}; Synonyms=D
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-5; Sequence=External;
CC Name=VII {ECO:0000250|UniProtKB:P12252}; Synonyms=L
CC {ECO:0000303|PubMed:10731132};
CC IsoId=P12252-6; 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}.
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DR EMBL; AE014298; AAN09606.1; -; Genomic_DNA.
DR RefSeq; NP_525061.2; NM_080322.3. [Q8IRU4-1]
DR AlphaFoldDB; Q8IRU4; -.
DR SMR; Q8IRU4; -.
DR BioGRID; 57834; 17.
DR DNASU; 31309; -.
DR EnsemblMetazoa; FBtr0070521; FBpp0070497; FBgn0000479. [Q8IRU4-1]
DR GeneID; 31309; -.
DR KEGG; dme:Dmel_CG32498; -.
DR UCSC; CG32498-RA; d. melanogaster. [Q8IRU4-1]
DR CTD; 31309; -.
DR FlyBase; FBgn0000479; dnc.
DR VEuPathDB; VectorBase:FBgn0000479; -.
DR GeneTree; ENSGT00940000155190; -.
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; Q8IRU4; baseline and differential.
DR Genevisible; Q8IRU4; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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: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:0007613; P:memory; 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 3: Inferred from homology;
KW Alternative initiation; Alternative splicing; cAMP; Hydrolase;
KW Metal-binding; Reference proteome.
FT CHAIN 1..662
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase,
FT isoform F"
FT /id="PRO_0000198820"
FT DOMAIN 248..577
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 79..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 599..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..632
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 324
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 324..328
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 364
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 482
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 482
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 533
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT SITE 485
FT /note="Binds AMP, but not cAMP"
FT /evidence="ECO:0000250"
SQ SEQUENCE 662 AA; 72954 MW; D195C7DAFCBD3CC3 CRC64;
MLNKNSASSQ SLPRVHSFFN MIPSIMQDDL ALTILNDRDN MFSIKSQRSH GEDLIVTPFA
QILASLRSVR NNLLSLTNVP ASNKSRRPNQ SSSASRSGNP PGAPLSQGEE AYTRLATDTI
EELDWCLDQL ETIQTHRSVS DMASLKFKRM LNKELSHFSE SSRSGNQISE YICSTFLDKQ
QEFDLPSLRV EDNPELVAAN AAAGQQSAGQ YARSRSPRGP PMSQISGVKR PLSHTNSFTG
ERLPTFGVET PRENELGTLL GELDTWGIQI FSIGEFSVNR PLTCVAYTIF QSRELLTSLM
IPPKTFLNFM STLEDHYVKD NPFHNSLHAA DVTQSTNVLL NTPALEGVFT PLEVGGALFA
ACIHDVDHPG LTNQFLVNSS SELALMYNDE SVLENHHLAV AFKLLQNQGC DIFCNMQKKQ
RQTLRKMVID IVLSTDMSKH MSLLADLKTM VETKKVAGSG VLLLDNYTDR IQVLENLVHC
ADLSNPTKPL PLYKRWVALL MEEFFLQGDK ERESGMDISP MCDRHNATIE KSQVGFIDYI
VHPLWETWAD LVHPDAQDIL DTLEENRDYY QSMIPPSPPP SGVDENPQED RIRFQVTLEE
SDQENLAELE EGDESGGEST TTGTTGTTAA SALSGAGGGG GGGGGMAPRT GGCQNQPQHG
GM
