PDE8_DROME
ID PDE8_DROME Reviewed; 914 AA.
AC Q6NNF2; E1JGU3; Q5BI98; Q8MLR0; Q95T53; Q9W1L9;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 {ECO:0000305};
DE EC=3.1.4.53 {ECO:0000250|UniProtKB:O95263};
DE AltName: Full=Phosphodiesterase 8 {ECO:0000312|FlyBase:FBgn0266377};
GN Name=Pde8 {ECO:0000312|FlyBase:FBgn0266377};
GN ORFNames=CG45019 {ECO:0000312|FlyBase:FBgn0266377},
GN CG5411 {ECO:0000312|EMBL:AAR96128.1};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAL25366.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL25366.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL25366.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000312|EMBL:AAR96128.1, ECO:0000312|EMBL:AAX33474.1, ECO:0000312|EMBL:AEX98031.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A; B AND E).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAR96128.1, ECO:0000312|EMBL:AAX33474.1,
RC ECO:0000312|EMBL:AEX98031.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAR96128.1, ECO:0000312|EMBL:AAX33474.1};
RA Stapleton M., Carlson J., Chavez C., George R., Pacleb J., Rubin G.M.,
RA Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JAN-2012) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=15673286; DOI=10.1042/bj20050057;
RA Day J.P., Dow J.A.T., Houslay M.D., Davies S.A.;
RT "Cyclic nucleotide phosphodiesterases in Drosophila melanogaster.";
RL Biochem. J. 388:333-342(2005).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23509299; DOI=10.1073/pnas.1303004110;
RA Brown K.M., Day J.P., Huston E., Zimmermann B., Hampel K., Christian F.,
RA Romano D., Terhzaz S., Lee L.C., Willis M.J., Morton D.B., Beavo J.A.,
RA Shimizu-Albergine M., Davies S.A., Kolch W., Houslay M.D., Baillie G.S.;
RT "Phosphodiesterase-8A binds to and regulates Raf-1 kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1533-E1542(2013).
CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key
CC regulator of many important physiological processes (By similarity).
CC Involved in the positive regulation of MAP kinase signaling and in
CC inhibiting oxidative stress-induced cell death (PubMed:23509299).
CC {ECO:0000250|UniProtKB:O60658, ECO:0000269|PubMed:23509299}.
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:O95263};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250|UniProtKB:O60658};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000250|UniProtKB:O60658}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=A {ECO:0000312|FlyBase:FBgn0266377};
CC IsoId=Q6NNF2-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0266377};
CC IsoId=Q6NNF2-2; Sequence=VSP_058755;
CC Name=C {ECO:0000312|FlyBase:FBgn0266377};
CC IsoId=Q6NNF2-3; Sequence=VSP_058753;
CC Name=E {ECO:0000312|FlyBase:FBgn0266377};
CC IsoId=Q6NNF2-4; Sequence=VSP_058756;
CC Name=O {ECO:0000312|FlyBase:FBgn0266377};
CC IsoId=Q6NNF2-5; Sequence=VSP_058754;
CC -!- TISSUE SPECIFICITY: Expressed in Malpighian tubules and head.
CC {ECO:0000269|PubMed:15673286}.
CC -!- DISRUPTION PHENOTYPE: Basal levels of phosphorylated kinase p38a/ERK2
CC are decreased significantly. Increased sensitivity to oxidative stress-
CC induced death. {ECO:0000269|PubMed:23509299}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE8 subfamily. {ECO:0000305}.
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DR EMBL; AE013599; AAF47038.3; -; Genomic_DNA.
DR EMBL; AE013599; AAM68263.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68265.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68266.1; -; Genomic_DNA.
DR EMBL; AE013599; ACZ94546.1; -; Genomic_DNA.
DR EMBL; AE013599; ACZ94547.2; -; Genomic_DNA.
DR EMBL; AE013599; ACZ94548.1; -; Genomic_DNA.
DR EMBL; AY060327; AAL25366.1; -; mRNA.
DR EMBL; BT021326; AAX33474.1; -; mRNA.
DR EMBL; BT011336; AAR96128.1; -; mRNA.
DR EMBL; BT133111; AEX98031.1; -; mRNA.
DR RefSeq; NP_001163274.1; NM_001169803.2. [Q6NNF2-1]
DR RefSeq; NP_001163275.2; NM_001169804.2. [Q6NNF2-5]
DR RefSeq; NP_001163276.1; NM_001169805.2. [Q6NNF2-1]
DR RefSeq; NP_611814.3; NM_137970.5. [Q6NNF2-4]
DR RefSeq; NP_726350.1; NM_166616.3. [Q6NNF2-1]
DR RefSeq; NP_726352.1; NM_166618.3. [Q6NNF2-2]
DR RefSeq; NP_726353.1; NM_166619.2. [Q6NNF2-3]
DR AlphaFoldDB; Q6NNF2; -.
DR SMR; Q6NNF2; -.
DR IntAct; Q6NNF2; 1.
DR STRING; 7227.FBpp0291341; -.
DR PRIDE; Q6NNF2; -.
DR DNASU; 37741; -.
DR EnsemblMetazoa; FBtr0344176; FBpp0310588; FBgn0266377. [Q6NNF2-3]
DR EnsemblMetazoa; FBtr0344178; FBpp0310590; FBgn0266377. [Q6NNF2-4]
DR EnsemblMetazoa; FBtr0344179; FBpp0310591; FBgn0266377. [Q6NNF2-2]
DR EnsemblMetazoa; FBtr0344180; FBpp0310592; FBgn0266377. [Q6NNF2-1]
DR EnsemblMetazoa; FBtr0344182; FBpp0310594; FBgn0266377. [Q6NNF2-1]
DR EnsemblMetazoa; FBtr0344183; FBpp0310595; FBgn0266377. [Q6NNF2-1]
DR EnsemblMetazoa; FBtr0344184; FBpp0310596; FBgn0266377. [Q6NNF2-5]
DR GeneID; 37741; -.
DR KEGG; dme:Dmel_CG45019; -.
DR UCSC; CG5411-RA; d. melanogaster. [Q6NNF2-1]
DR UCSC; CG5411-RB; d. melanogaster.
DR UCSC; CG5411-RC; d. melanogaster.
DR UCSC; CG5411-RE; d. melanogaster.
DR CTD; 37741; -.
DR FlyBase; FBgn0266377; Pde8.
DR VEuPathDB; VectorBase:FBgn0266377; -.
DR eggNOG; KOG1229; Eukaryota.
DR GeneTree; ENSGT00940000168652; -.
DR InParanoid; Q6NNF2; -.
DR PhylomeDB; Q6NNF2; -.
DR Reactome; R-DME-418555; G alpha (s) signalling events.
DR UniPathway; UPA00762; UER00747.
DR BioGRID-ORCS; 37741; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Pde8; fly.
DR GenomeRNAi; 37741; -.
DR PRO; PR:Q6NNF2; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0266377; Expressed in seminal fluid secreting gland and 25 other tissues.
DR ExpressionAtlas; Q6NNF2; baseline and differential.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISM: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:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046058; P:cAMP metabolic process; ISM:FlyBase.
DR GO; GO:0007498; P:mesoderm development; IEP:FlyBase.
DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR Pfam; PF13426; PAS_9; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50112; PAS; 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..914
FT /note="High affinity cAMP-specific and IBMX-insensitive
FT 3',5'-cyclic phosphodiesterase 8"
FT /id="PRO_0000438862"
FT DOMAIN 312..359
FT /note="PAS"
FT /evidence="ECO:0000305"
FT DOMAIN 558..893
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 113..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 113..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 640
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 644
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60658"
FT BINDING 682
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60658"
FT BINDING 683
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60658"
FT BINDING 683
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60658"
FT BINDING 799
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60658"
FT VAR_SEQ 1..514
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_058753"
FT VAR_SEQ 1..154
FT /note="MGCSPSTLPPAPSAGQTGERGSLPLDASEKDESRLFCIKLRRSRLRRCSCGG
FT VTLQPPSDGNGSTAGDNLCGQVLLNPLQTKSEADYEKLSTGKKDSIVTVAALGNFTHSV
FT VRRATGSTGTSGTSSSGGNSRPGHRKSSLALALTPEDEPMDVY -> MRNCLPKFSKVF
FT RRKSSAKSSSSSAGRENPSSEPDSDTEPYAIAIAAISDRSGDNRNERPRPLPDDDSIRS
FT RLISAAHLDLDVGLELASDSTAVPANGGIRPKSEGACPEMKVETISAATSPPPPRPLHG
FT TSGPVAISLPFVGRNSSKTPEEMELEYEANVEAESRDIMTPLRRNTRPLSVSFGGGGGR
FT SALQPEIVEAIRSLDVPALRLNNLSFDGSTDPKGERNHAEEEPLTPGHDHEDSVVLRRK
FT VNCLERKAHSLYERRLPRVPKLHLLVAGKKNPPTEEEEFRTF (in isoform O)"
FT /evidence="ECO:0000305"
FT /id="VSP_058754"
FT VAR_SEQ 1..118
FT /note="MGCSPSTLPPAPSAGQTGERGSLPLDASEKDESRLFCIKLRRSRLRRCSCGG
FT VTLQPPSDGNGSTAGDNLCGQVLLNPLQTKSEADYEKLSTGKKDSIVTVAALGNFTHSV
FT VRRATGS -> MIISSQPNLAGSATTTTTTTISSAHVSQEGTMPLPLPIPVTMPLPNAG
FT TCNCGAVGVGVGVGMGMALGARQCPSPAVDPTTATATPTSTTPGRDSLTRPASESELNV
FT G (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_058755"
FT VAR_SEQ 479..487
FT /note="Missing (in isoform E)"
FT /evidence="ECO:0000305"
FT /id="VSP_058756"
SQ SEQUENCE 914 AA; 102052 MW; F18DED7AC544B0EC CRC64;
MGCSPSTLPP APSAGQTGER GSLPLDASEK DESRLFCIKL RRSRLRRCSC GGVTLQPPSD
GNGSTAGDNL CGQVLLNPLQ TKSEADYEKL STGKKDSIVT VAALGNFTHS VVRRATGSTG
TSGTSSSGGN SRPGHRKSSL ALALTPEDEP MDVYQRNLMD LKYPTVLPPN PPLKALLVFH
KSDSICEAIT AACQRHQLDV TLVKSKEEAL DTLQKSYATA QCYHLIIIDA RSSKNLDAEH
IARTIRHTHG HHLTTIIAVC KKSFFEKDDV LIALLDAGVN RCVAETTNLA MCSVELKQIL
HSIIRPHNVM STQQALYTAL HRLKEVVLIT DDLLRIQYAN RATERLLNMR LDEIISKQLE
DIFVSDLSTI SEQCKNIKEF DGILTVRRKS QEGIPMHVRV VPVACIGSAP THLIFNFDVP
GGQMDFIATL PQPKEAPRGS LHSVRRCSFD VRSIASDGLR RTSLAKLTSL PLEAPITKII
NLLSQVQENC SADEARLIDK VLEFLKREGL YSPQMKEIRT DDPIATDLIG ALLTGPSVYS
SRRSSNDSII RTGSSTRTAA IVPAKMKSNP IIMELLDESL SWDFDIFKLE EITDYHPLLY
LGMEMFRRFD VFATLNIDEN VCKAWLAVIE AHYRKSNTYH NSTHAADVMQ ATGAFITQLT
NKDMLVMDRM EEATALIAAA AHDVDHPGRS SAFLCNSNDA LAVLYNDLTV LENHHAAITF
KLTLGDDKIN IFKNLDKETY KSARSTIIDM ILATEMTRHF EHLAKFVSVF GGEEPRDHNP
QTDEETSILM RRMLIKVADV SNPARPMQFC IEWARRIAEE YFMQTDEEKQ RHLPIVMPMF
DRATCSIPKS QIGFIEYIIQ DMMHAWESFI DMPQLITYMQ INYSQWKKYD EQGVNTLAEI
MAKQPPVGKM ANSK
