ID   PDE4_CAEEL              Reviewed;         674 AA.
AC   Q22000; Q86NE7; Q86NE8; Q86NE9; Q8IFZ3; Q95ZQ6;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 2.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Probable 3',5'-cyclic-AMP phosphodiesterase pde-4 {ECO:0000305};
DE            EC=3.1.4.53 {ECO:0000250|UniProtKB:P27815};
GN   Name=pde-4; ORFNames=R153.1;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=29033363; DOI=10.1016/j.devcel.2017.09.013;
RA   Yu B., Wang X., Wei S., Fu T., Dzakah E.E., Waqas A., Walthall W.W.,
RA   Shan G.;
RT   "Convergent Transcriptional Programs Regulate cAMP Levels in C. elegans
RT   GABAergic Motor Neurons.";
RL   Dev. Cell 43:212-226(2017).
CC   -!- FUNCTION: Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP),
CC       which is a key regulator of many important physiological processes (By
CC       similarity). Antagonizes dorsal D (DD) motor neuron respecification by
CC       reducing levels of cAMP (PubMed:29033363).
CC       {ECO:0000250|UniProtKB:P27815, ECO:0000269|PubMed:29033363}.
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:P27815};
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   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=d;
CC         IsoId=Q22000-1; Sequence=Displayed;
CC       Name=a;
CC         IsoId=Q22000-2; Sequence=VSP_014345, VSP_014352;
CC       Name=b;
CC         IsoId=Q22000-3; Sequence=VSP_014347, VSP_014350;
CC       Name=c;
CC         IsoId=Q22000-4; Sequence=VSP_014346, VSP_014351;
CC       Name=e;
CC         IsoId=Q22000-5; Sequence=VSP_014348, VSP_014349;
CC       Name=f;
CC         IsoId=Q22000-6; Sequence=VSP_014353, VSP_014354;
CC   -!- TISSUE SPECIFICITY: Expressed in dorsal D (DD) motor neurons and
CC       several other neurons at the L1 stage. Expression in DD neurons
CC       decreases gradually beginning in the late L1 stage. Highly expressed in
CC       adult ventral D (VD) motor neurons, but diminished in adult DD motor
CC       neurons. {ECO:0000269|PubMed:29033363}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       {ECO:0000305}.
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DR   EMBL; FO081170; CCD69643.1; -; Genomic_DNA.
DR   EMBL; FO081170; CCD69647.1; -; Genomic_DNA.
DR   EMBL; FO081170; CCD69649.1; -; Genomic_DNA.
DR   EMBL; FO081170; CCD69644.1; -; Genomic_DNA.
DR   EMBL; FO081170; CCD69648.1; -; Genomic_DNA.
DR   EMBL; FO081170; CCD69645.1; -; Genomic_DNA.
DR   PIR; T16769; T16769.
DR   RefSeq; NP_495600.1; NM_063199.3. [Q22000-5]
DR   RefSeq; NP_495601.1; NM_063200.1. [Q22000-2]
DR   RefSeq; NP_871944.1; NM_182144.3.
DR   RefSeq; NP_871945.1; NM_182145.3. [Q22000-1]
DR   RefSeq; NP_871946.1; NM_182146.3.
DR   RefSeq; NP_871947.1; NM_182147.3. [Q22000-6]
DR   AlphaFoldDB; Q22000; -.
DR   SMR; Q22000; -.
DR   BioGRID; 39569; 2.
DR   STRING; 6239.R153.1d.1; -.
DR   EPD; Q22000; -.
DR   PaxDb; 6239-R153-1d; -.
DR   PeptideAtlas; Q22000; -.
DR   EnsemblMetazoa; R153.1a.1; R153.1a.1; WBGene00020114. [Q22000-2]
DR   EnsemblMetazoa; R153.1b.1; R153.1b.1; WBGene00020114. [Q22000-5]
DR   EnsemblMetazoa; R153.1c.1; R153.1c.1; WBGene00020114. [Q22000-4]
DR   EnsemblMetazoa; R153.1d.1; R153.1d.1; WBGene00020114. [Q22000-1]
DR   EnsemblMetazoa; R153.1e.1; R153.1e.1; WBGene00020114. [Q22000-3]
DR   EnsemblMetazoa; R153.1e.2; R153.1e.2; WBGene00020114. [Q22000-3]
DR   EnsemblMetazoa; R153.1f.1; R153.1f.1; WBGene00020114. [Q22000-6]
DR   GeneID; 174235; -.
DR   UCSC; R153.1b; c. elegans. [Q22000-1]
DR   AGR; WB:WBGene00020114; -.
DR   WormBase; R153.1a; CE02038; WBGene00020114; pde-4. [Q22000-2]
DR   WormBase; R153.1b; CE28641; WBGene00020114; pde-4. [Q22000-5]
DR   WormBase; R153.1c; CE32060; WBGene00020114; pde-4. [Q22000-4]
DR   WormBase; R153.1d; CE33438; WBGene00020114; pde-4. [Q22000-1]
DR   WormBase; R153.1e; CE33439; WBGene00020114; pde-4. [Q22000-3]
DR   WormBase; R153.1f; CE33440; WBGene00020114; pde-4. [Q22000-6]
DR   eggNOG; KOG3689; Eukaryota.
DR   HOGENOM; CLU_005940_8_0_1; -.
DR   InParanoid; Q22000; -.
DR   OMA; WTERVMA; -.
DR   OrthoDB; 240889at2759; -.
DR   PhylomeDB; Q22000; -.
DR   Reactome; R-CEL-180024; DARPP-32 events.
DR   Reactome; R-CEL-418555; G alpha (s) signalling events.
DR   PRO; PR:Q22000; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00020114; Expressed in larva and 3 other cell types or tissues.
DR   ExpressionAtlas; Q22000; baseline and differential.
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; IDA:WormBase.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISS:WormBase.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0006198; P:cAMP catabolic process; ISS:WormBase.
DR   GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IGI:WormBase.
DR   GO; GO:0040013; P:negative regulation of locomotion; IMP:WormBase.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0030431; P:sleep; IMP:WormBase.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 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   PANTHER; PTHR11347:SF219; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE, ISOFORM I; 1.
DR   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   Pfam; PF18100; PDE4_UCR; 1.
DR   Pfam; PF00233; PDEase_I; 1.
DR   PRINTS; PR00387; PDIESTERASE1.
DR   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; cAMP; Hydrolase; Metal-binding; Reference proteome.
FT   CHAIN           1..674
FT                   /note="Probable 3',5'-cyclic-AMP phosphodiesterase pde-4"
FT                   /id="PRO_0000198847"
FT   DOMAIN          328..660
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          1..82
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..16
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        37..55
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        62..82
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        407
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         411
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         447
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         448
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         448
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         565
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..125
FT                   /note="Missing (in isoform a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014345"
FT   VAR_SEQ         1..75
FT                   /note="Missing (in isoform c)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014346"
FT   VAR_SEQ         1..62
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014347"
FT   VAR_SEQ         1..48
FT                   /note="Missing (in isoform e)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014348"
FT   VAR_SEQ         49..91
FT                   /note="SRTPPAALPPRTSAVTIPGSNHKLTSSASSYHPPRELTVSTFS -> MCGSR
FT                   RHLRRNEDGMNGVARRKQFKLRPWQSTALPSRHDHYSC (in isoform e)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014349"
FT   VAR_SEQ         63..91
FT                   /note="VTIPGSNHKLTSSASSYHPPRELTVSTFS -> MNGVARRKQFKLRPWQSTA
FT                   LPSRHDHYSC (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014350"
FT   VAR_SEQ         76..90
FT                   /note="ASSYHPPRELTVSTF -> MTSRRHTVWFVPGSR (in isoform c)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014351"
FT   VAR_SEQ         126..150
FT                   /note="SDDLREASSLRPVSRASSIASNEHG -> MSISLINNNNRSVRRKFGESGFT
FT                   LR (in isoform a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014352"
FT   VAR_SEQ         151..158
FT                   /note="HGDDLIVT -> YVILYIFL (in isoform f)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014353"
FT   VAR_SEQ         159..674
FT                   /note="Missing (in isoform f)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_014354"
SQ   SEQUENCE   674 AA;  75389 MW;  87BA310BE45DBD30 CRC64;
     MPRRRGSSSS SSAAGGSGGG GGFGFSSLRR ELHLHNFFRT SSPSASSTSR TPPAALPPRT
     SAVTIPGSNH KLTSSASSYH PPRELTVSTF SAGSATAADG LGGAHLTPSL SSSVHARRES
     FLYRASDDLR EASSLRPVSR ASSIASNEHG HGDDLIVTPF AQLLASLRNV RSNLISITNI
     QNSDDSRHAN RSAKRPPLHN IELPDDVVHC AHDTLEELDW CLDQLETIQT HRSVSEMASS
     KFRKMLNKEL SHFAESSKSG TQVSKFLITT YMDKEEDEPS IEIEVPTEVQ GPSTSGPMTL
     SILKKAQTAA MNKISGVRKL RAPSHDGHVP EYGVNCAREI AVHMQRLDDW GPDVFKIDEL
     SKNHSLTVVT FSLLRQRNLF KTFEIHQSTL VTYLLNLEHH YRNNHYHNFI HAADVAQSMH
     VLLMSPVLTE VFTDLEVLAA IFAGAVHDVD HPGFTNQYLI NSNNELAIMY NDESVLEQHH
     LAVAFKLLQD SNCDFLANLS RKQRLQFRKI VIDMVLATDM SKHMSLLADL KTMVEAKKVA
     GNNVIVLDKY NDKIQVLQSM IHLADLSNPT KPIELYQQWN QRIMEEYWRQ GDKEKELGLE
     ISPMCDRGNV TIEKSQVGFI DYIVHPLYET WADLVYPDAQ NILDQLEENR EWYQSRIPEE
     PDTARTVTED DEHK
//