PDE4C_DROME
ID PDE4C_DROME Reviewed; 983 AA.
AC Q9W4S9; Q8IRU5;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase, isoforms N/G;
DE EC=3.1.4.53;
DE AltName: Full=Learning/memory process protein;
DE AltName: Full=Protein dunce;
GN Name=dnc {ECO:0000312|EMBL:AAF45863.2}; 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:AAF45863.2}
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:AAF45863.2}
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 170-479.
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).
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=N {ECO:0000303|PubMed:10731132};
CC IsoId=Q9W4S9-1; Sequence=Displayed;
CC Name=G {ECO:0000303|PubMed:10731132};
CC IsoId=Q9W4S9-2; Sequence=VSP_051775;
CC Name=F {ECO:0000303|PubMed:10731132};
CC IsoId=Q8IRU4-1; 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=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=CAB57995.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF45863.2; -; Genomic_DNA.
DR EMBL; AE014298; AAN09605.2; -; Genomic_DNA.
DR EMBL; AL121800; CAB57995.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_726856.1; NM_166968.3. [Q9W4S9-1]
DR RefSeq; NP_726858.2; NM_166970.2. [Q9W4S9-2]
DR AlphaFoldDB; Q9W4S9; -.
DR SMR; Q9W4S9; -.
DR BioGRID; 57834; 17.
DR IntAct; Q9W4S9; 1.
DR PRIDE; Q9W4S9; -.
DR DNASU; 31309; -.
DR EnsemblMetazoa; FBtr0070519; FBpp0070495; FBgn0000479. [Q9W4S9-1]
DR EnsemblMetazoa; FBtr0070520; FBpp0070496; FBgn0000479. [Q9W4S9-2]
DR GeneID; 31309; -.
DR UCSC; CG32498-RA; d. melanogaster. [Q9W4S9-1]
DR CTD; 31309; -.
DR FlyBase; FBgn0000479; dnc.
DR VEuPathDB; VectorBase:FBgn0000479; -.
DR GeneTree; ENSGT00940000155190; -.
DR HOGENOM; CLU_005940_3_0_1; -.
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; Q9W4S9; baseline and differential.
DR Genevisible; Q9W4S9; 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..983
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase,
FT isoforms N/G"
FT /id="PRO_0000198818"
FT DOMAIN 569..898
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 31..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 920..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..195
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..290
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 528..542
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..564
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..953
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 645
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 645..649
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 649
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 685
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 686
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 686
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 686
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 803
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 803
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 854
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT SITE 806
FT /note="Binds AMP, but not cAMP"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..169
FT /note="Missing (in isoform G)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_051775"
SQ SEQUENCE 983 AA; 107341 MW; 374785B501D6D73E CRC64;
MIATLFIIFA FIRAFPWSRK RGRPALALTL MPEGGEDHRG DLNQKGENNN RPRPSISLAN
NGEAMAPRTR RKSSKFHEVT FSGSVGGGDS DGGGEAINGG NLDVSPSKRH SLSTTTSNSS
SAPYRYLSGS SRSRGSRGDC HEYYQLQQHS SSLSNGNRGN RGLSQRSDTM ATEAEGEEFD
VDPMDEDDED QTYDRETEEF YSNIQDAAGT GSSSRSKRSS LFSRSDSSAT TTSSSGGGTF
TGGKRRSAAS ILSSSMCSDL MTSDRRSSTA TEYSVKSVTT GNTSQRRSSG RIRRYVSRMT
IAGARRRTTG SFDVENGQGA RSPLEGGSPS AGLVLQNLPQ RRESFLYRSD SDFEMSPKSM
SRNSSIASES HGEDLIVTPF AQILASLRSV RNNLLSLTNV PASNKSRRPN QSSSASRSGN
PPGAPLSQGE EAYTRLATDT IEELDWCLDQ LETIQTHRSV SDMASLKFKR MLNKELSHFS
ESSRSGNQIS EYICSTFLDK QQEFDLPSLR VEDNPELVAA NAAAGQQSAG QYARSRSPRG
PPMSQISGVK RPLSHTNSFT GERLPTFGVE TPRENELGTL LGELDTWGIQ IFSIGEFSVN
RPLTCVAYTI FQSRELLTSL MIPPKTFLNF MSTLEDHYVK DNPFHNSLHA ADVTQSTNVL
LNTPALEGVF TPLEVGGALF AACIHDVDHP GLTNQFLVNS SSELALMYND ESVLENHHLA
VAFKLLQNQG CDIFCNMQKK QRQTLRKMVI DIVLSTDMSK HMSLLADLKT MVETKKVAGS
GVLLLDNYTD RIQVLENLVH CADLSNPTKP LPLYKRWVAL LMEEFFLQGD KERESGMDIS
PMCDRHNATI EKSQVGFIDY IVHPLWETWA DLVHPDAQDI LDTLEENRDY YQSMIPPSPP
PSGVDENPQE DRIRFQVTLE ESDQENLAEL EEGDESGGES TTTGTTGTTA ASALSGAGGG
GGGGGGMAPR TGGCQNQPQH GGM
