PDE9A_DROME
ID PDE9A_DROME Reviewed; 1526 AA.
AC Q9I7S6;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A {ECO:0000305};
DE EC=3.1.4.35 {ECO:0000250|UniProtKB:O76083};
DE AltName: Full=Phosphodiesterase 9 {ECO:0000303|PubMed:15673286};
GN Name=Pde9 {ECO:0000312|FlyBase:FBgn0259171};
GN ORFNames=CG42276 {ECO:0000312|FlyBase:FBgn0259171};
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: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).
CC -!- FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a
CC key regulator of many important physiological processes. Highly
CC specific: compared to other members of the cyclic nucleotide
CC phosphodiesterase family, has the highest affinity and selectivity for
CC cGMP. {ECO:0000250|UniProtKB:O76083}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; EC=3.1.4.35;
CC Evidence={ECO:0000250|UniProtKB:O76083};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O76083};
CC Note=Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per
CC subunit: site 1 preferentially binds zinc, while site 2 has a
CC preference for magnesium. Tightly binds zinc.
CC {ECO:0000250|UniProtKB:O76083};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O76083};
CC Note=Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations
CC per subunit: site 1 preferentially binds zinc, while site 2 has a
CC preference for magnesium. Binds magnesium less tightly than zinc.
CC {ECO:0000250|UniProtKB:O76083};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC 3',5'-cyclic GMP: step 1/1. {ECO:0000250|UniProtKB:O76083}.
CC -!- TISSUE SPECIFICITY: Expressed in Malpighian tubules and adult fly head.
CC {ECO:0000269|PubMed:15673286}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE9 subfamily. {ECO:0000305}.
CC -!- CAUTION: No activity observed following immunoprecipitation from adult
CC head (PubMed:15673286). However, it is likely that the protein has
CC phosphodiesterase activity based on the conservation of the active site
CC as well as nucleotide-binding and metal-binding sites.
CC {ECO:0000269|PubMed:15673286, ECO:0000305}.
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DR EMBL; AE014298; AAG22348.2; -; Genomic_DNA.
DR EMBL; AE014298; AGB95337.1; -; Genomic_DNA.
DR EMBL; AE014298; AGB95338.1; -; Genomic_DNA.
DR RefSeq; NP_001259495.1; NM_001272566.1.
DR RefSeq; NP_001259496.1; NM_001272567.2.
DR RefSeq; NP_572834.2; NM_132606.5.
DR AlphaFoldDB; Q9I7S6; -.
DR SMR; Q9I7S6; -.
DR IntAct; Q9I7S6; 3.
DR STRING; 7227.FBpp0305705; -.
DR PRIDE; Q9I7S6; -.
DR EnsemblMetazoa; FBtr0299635; FBpp0288910; FBgn0259171.
DR EnsemblMetazoa; FBtr0333524; FBpp0305704; FBgn0259171.
DR EnsemblMetazoa; FBtr0333525; FBpp0305705; FBgn0259171.
DR GeneID; 32233; -.
DR KEGG; dme:Dmel_CG42276; -.
DR CTD; 32233; -.
DR FlyBase; FBgn0259171; Pde9.
DR VEuPathDB; VectorBase:FBgn0259171; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000165301; -.
DR HOGENOM; CLU_246554_0_0_1; -.
DR OMA; NWLCLSN; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q9I7S6; -.
DR UniPathway; UPA00763; UER00748.
DR BioGRID-ORCS; 32233; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32233; -.
DR PRO; PR:Q9I7S6; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0259171; Expressed in brain and 19 other tissues.
DR ExpressionAtlas; Q9I7S6; baseline and differential.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISM:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046069; P:cGMP catabolic process; IBA:GO_Central.
DR GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0009187; P:cyclic nucleotide metabolic process; ISM:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 2: Evidence at transcript level;
KW cGMP; Hydrolase; Magnesium; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..1526
FT /note="High affinity cGMP-specific 3',5'-cyclic
FT phosphodiesterase 9A"
FT /id="PRO_0000438863"
FT DOMAIN 664..985
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 986..1170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1265..1284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1314..1351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1372..1406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1469..1496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..348
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 988..1017
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1057..1096
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1121..1140
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1265..1281
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1314..1328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1372..1400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1469..1490
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 740
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 740..744
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 744
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 780
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 781
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 781
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 890
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 890
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O76083"
SQ SEQUENCE 1526 AA; 162819 MW; E3B5EA9223D6768B CRC64;
MYQDSGCSSS SSRRGSSSAA AATSTAATAA ETAAAAAATT TSSSDEETLE TLTIITTTIT
DSDIHATTTT TTVIASGTAT TAAAAATTAT LATLATLASN SDIEDSSPVE SEDSEECEYI
EIDCQTTAQE GTSPSGGSSS SGNAVLLQRS SNNLQQQQQQ QQQQQQHLQL QLQQADERLL
RKIGYIASRV RCLSKYYGDF RLVNPYSARR QRRQLQEILL RHSIFDPGKE HQRAIVLAAA
TAAIAGPLAA IDCVCGSSSI SLEAVSSRSR SSELEDDHHE QDQVQEEQEQ EQHQGDTEDN
EEEQEHPSEK PERTDIEEEP PPAIAVTTTT TATVRRKSSS SSTISGTATV SGSVSVSASA
SQSFCSNNIN LLEELLIQFY EEQDHRSNLT VIRHHHHQQH QQHQQQQRIT NNNNNNNNCN
SIQNNNNMSN PAATAAATAT PSVEQPATSG TTNIHLQPTS LPDGSDNPRR RRASDCSAVQ
AALQNQLHCI TLKNNNCGKA MPFHRGSCGA AGEHLLAANS IANRATIILS KSCSNVDGDA
TATAATALSS TVGGGIGGIG GSIKMRASAT DIETNALNGA RDAIVASNNG NNGNNGNNGN
NEYSILQLNN TIIQCHFNDD DFRALVKDLK RKVEYTERMN WLCLSKRPLG PPHRKSSLPK
HQEVKRRFLE ICDTTFSEEV RAALRLPAFD SYEWSDADVI HLMQTMFVEL GFIEKFSIPV
DTLREWLYEV YKHYNEVPFH NFRHCFCVAQ MMYAITRQAN LLSRLGDLEC LILLVSCICH
DLDHPGYNNI YQINARTELA LRYNDISPLE NHHCSIAFRL LEHPECNIFK NFSRDTFNNI
REGIIRCILA TDMARHNEIL TQFMEITPIF DYSNRAHINL LCMILIKVAD ISNEARPMDV
AEPWLDRLLQ EFFAQSAAEK SEGLPVTPFM DPDKVSKPGS QVRFIGLVLL PLFEALGELV
PELTELIIIP VRIALEYYRR LNDAQTKTRK SVADSNTSAT SDSNSGTIDS NAAMVSTPGG
ASDKLSLDKG QGNSQGSGGG GGGGGGGGAG GGTGSGCGSN AAGSVSPQMP RSGSGISVKS
RRSIPSQKSA SRTSVDEPGG MASELHDLPE GSESGDSETA TEVDVAEKTS KFKVDTEGSS
NRSKSSHSTS RKSSREKRPS MIGELCSSGG GQRIRNSYGN IHGYHSNRCH FGNNRAVSLD
QYSSAGNNRR LSDGLPQVIS DSNVFYGRHN RSSTETTVAV GNPQDTNANT NHPVGCQLKE
LLARTEADSD GEGDGNGRED KKIPLVIPSM PQLATSSNGN ISPTLVVTEQ ILPSNGSTRS
SASSGRGGSG VPGGSGGSGM PGPSAGSGSS WKSRLRQFSD YFSFSFDKSN KRFGSTRSSP
CPGSNSSSGR TNNNANGLGE NQDGLGAGGG IKPGMCCTTI TNSSGSTVKG ETRGGTAGAG
GGALTTMTTG NDAHQRHRAY SLDVPGMMRY SSNDSSRHPS NNTLQSAGGG AGLTTGLEVT
AQRVPPSLSV EMGLASGSSS EAGPKI
