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Database: UniProt
Entry: Q9QYJ6
LinkDB: Q9QYJ6
Original site: Q9QYJ6 
ID   PDE10_RAT               Reviewed;         794 AA.
AC   Q9QYJ6; Q6S9E6; Q6S9E7; Q6S9E8; Q6S9E9; Q9QYJ5;
DT   16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   29-SEP-2021, entry version 124.
DE   RecName: Full=cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A;
DE            EC=3.1.4.17 {ECO:0000269|PubMed:10583409, ECO:0000269|PubMed:14752115};
GN   Name=Pde10a;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING,
RP   FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP   REGULATION, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=10583409; DOI=10.1046/j.1432-1327.1999.00963.x;
RA   Fujishige K., Kotera J., Omori K.;
RT   "Striatum- and testis-specific phosphodiesterase PDE10A isolation and
RT   characterization of a rat PDE10A.";
RL   Eur. J. Biochem. 266:1118-1127(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5 AND 6), TISSUE SPECIFICITY,
RP   CATALYTIC ACTIVITY, AND INDUCTION.
RC   STRAIN=Wistar;
RX   PubMed=14752115; DOI=10.1074/jbc.m312500200;
RA   O'Connor V., Genin A., Davis S., Karishma K.K., Doyere V., De Zeeuw C.I.,
RA   Sanger G., Hunt S.P., Richter-Levin G., Mallet J., Laroche S.,
RA   Bliss T.V.P., French P.J.;
RT   "Differential amplification of intron-containing transcripts reveals long
RT   term potentiation-associated up-regulation of specific Pde10A
RT   phosphodiesterase splice variants.";
RL   J. Biol. Chem. 279:15841-15849(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 452-794 IN COMPLEXES WITH ZINC;
RP   MAGNESIUM AND A SYNTHETIC INHIBITOR.
RX   PubMed=17228859; DOI=10.1021/jm060653b;
RA   Chappie T.A., Humphrey J.M., Allen M.P., Estep K.G., Fox C.B., Lebel L.A.,
RA   Liras S., Marr E.S., Menniti F.S., Pandit J., Schmidt C.J., Tu M.,
RA   Williams R.D., Yang F.V.;
RT   "Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A
RT   inhibitors.";
RL   J. Med. Chem. 50:182-185(2007).
CC   -!- FUNCTION: Plays a role in signal transduction by regulating the
CC       intracellular concentration of cyclic nucleotides. Can hydrolyze both
CC       cAMP and cGMP, but has higher affinity for cAMP and is more efficient
CC       with cAMP as substrate. {ECO:0000269|PubMed:10583409}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-
CC         phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
CC         Evidence={ECO:0000269|PubMed:10583409, ECO:0000269|PubMed:14752115};
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; Evidence={ECO:0000269|PubMed:10583409};
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; Evidence={ECO:0000269|PubMed:10583409,
CC         ECO:0000269|PubMed:14752115};
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
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.;
CC   -!- ACTIVITY REGULATION: Inhibited by dipyridamole and moderately by IBMX,
CC       zaprinast and rolipram. {ECO:0000269|PubMed:10583409}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.26 uM for cAMP {ECO:0000269|PubMed:10583409};
CC         KM=9.3 uM for cGMP {ECO:0000269|PubMed:10583409};
CC   -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC       3',5'-cyclic AMP: step 1/1.
CC   -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC       3',5'-cyclic GMP: step 1/1.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10583409}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1; Synonyms=PDE10A2;
CC         IsoId=Q9QYJ6-1; Sequence=Displayed;
CC       Name=2; Synonyms=PDE10A3;
CC         IsoId=Q9QYJ6-2; Sequence=VSP_035921;
CC       Name=3; Synonyms=PDE10A11;
CC         IsoId=Q9QYJ6-3; Sequence=VSP_035922;
CC       Name=4; Synonyms=PDE10A12;
CC         IsoId=Q9QYJ6-4; Sequence=VSP_035923;
CC       Name=5; Synonyms=PDE10A13;
CC         IsoId=Q9QYJ6-5; Sequence=VSP_035920;
CC       Name=6; Synonyms=PDE10A14;
CC         IsoId=Q9QYJ6-6; Sequence=VSP_035919;
CC   -!- TISSUE SPECIFICITY: Detected in striatum and testis (at protein level).
CC       Detected in whole brain, hippocampus, olfactory bulb, striatum neurons
CC       and testis. {ECO:0000269|PubMed:10583409, ECO:0000269|PubMed:14752115}.
CC   -!- INDUCTION: Up-regulated in brain after seizures. Up-regulated in the
CC       hippocampus one hour after induction of long-term potentiation.
CC       {ECO:0000269|PubMed:14752115}.
CC   -!- DOMAIN: The tandem GAF domains bind cAMP, and regulate enzyme activity.
CC       The binding of cAMP stimulates enzyme activity.
CC   -!- DOMAIN: Composed of a C-terminal catalytic domain containing two
CC       divalent metal sites and an N-terminal regulatory domain which contains
CC       one cyclic nucleotide-binding region.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       {ECO:0000305}.
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DR   EMBL; AB027155; BAA88996.1; -; mRNA.
DR   EMBL; AB027156; BAA88997.1; -; mRNA.
DR   EMBL; AY462091; AAS21243.1; -; mRNA.
DR   EMBL; AY462092; AAS21244.1; -; mRNA.
DR   EMBL; AY462093; AAS21245.1; -; mRNA.
DR   EMBL; AY462094; AAS21246.1; -; mRNA.
DR   EMBL; AY462095; AAS21247.1; -; mRNA.
DR   EMBL; CH474059; EDL83106.1; -; Genomic_DNA.
DR   RefSeq; NP_071572.1; NM_022236.1. [Q9QYJ6-1]
DR   PDB; 2O8H; X-ray; 1.80 A; A=452-794.
DR   PDB; 2OVV; X-ray; 2.00 A; A=452-794.
DR   PDB; 2OVY; X-ray; 1.80 A; A=452-794.
DR   PDB; 3HQW; X-ray; 1.70 A; A=452-794.
DR   PDB; 3HQY; X-ray; 2.00 A; A=452-794.
DR   PDB; 3HQZ; X-ray; 1.70 A; A=452-794.
DR   PDB; 3HR1; X-ray; 1.53 A; A=452-794.
DR   PDB; 3LXG; X-ray; 2.30 A; A=463-770.
DR   PDB; 3QPN; X-ray; 2.00 A; A=452-794.
DR   PDB; 3QPO; X-ray; 1.80 A; A=452-794.
DR   PDB; 3QPP; X-ray; 1.80 A; A=452-794.
DR   PDB; 6K9U; X-ray; 2.35 A; A=463-770.
DR   PDBsum; 2O8H; -.
DR   PDBsum; 2OVV; -.
DR   PDBsum; 2OVY; -.
DR   PDBsum; 3HQW; -.
DR   PDBsum; 3HQY; -.
DR   PDBsum; 3HQZ; -.
DR   PDBsum; 3HR1; -.
DR   PDBsum; 3LXG; -.
DR   PDBsum; 3QPN; -.
DR   PDBsum; 3QPO; -.
DR   PDBsum; 3QPP; -.
DR   PDBsum; 6K9U; -.
DR   SMR; Q9QYJ6; -.
DR   BioGRID; 248919; 1.
DR   STRING; 10116.ENSRNOP00000060834; -.
DR   BindingDB; Q9QYJ6; -.
DR   ChEMBL; CHEMBL6140; -.
DR   DrugCentral; Q9QYJ6; -.
DR   iPTMnet; Q9QYJ6; -.
DR   SwissPalm; Q9QYJ6; -.
DR   PaxDb; Q9QYJ6; -.
DR   Ensembl; ENSRNOT00000043474; ENSRNOP00000042134; ENSRNOG00000011310. [Q9QYJ6-1]
DR   GeneID; 63885; -.
DR   KEGG; rno:63885; -.
DR   CTD; 10846; -.
DR   RGD; 68434; Pde10a.
DR   eggNOG; KOG3689; Eukaryota.
DR   GeneTree; ENSGT00940000156543; -.
DR   InParanoid; Q9QYJ6; -.
DR   OMA; QIYARIF; -.
DR   OrthoDB; 904682at2759; -.
DR   TreeFam; TF316499; -.
DR   Reactome; R-RNO-418457; cGMP effects.
DR   Reactome; R-RNO-418555; G alpha (s) signalling events.
DR   SABIO-RK; Q9QYJ6; -.
DR   UniPathway; UPA00762; UER00747.
DR   UniPathway; UPA00763; UER00748.
DR   EvolutionaryTrace; Q9QYJ6; -.
DR   PRO; PR:Q9QYJ6; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Proteomes; UP000234681; Chromosome 1.
DR   Proteomes; UP000234681; Unassembled WGS sequence.
DR   Bgee; ENSRNOG00000011310; Expressed in frontal cortex and 21 other tissues.
DR   ExpressionAtlas; Q9QYJ6; baseline and differential.
DR   Genevisible; Q9QYJ6; RN.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0043204; C:perikaryon; IDA:RGD.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:RHEA.
DR   GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:RHEA.
DR   GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; ISO:RGD.
DR   GO; GO:0030552; F:cAMP binding; ISO:RGD.
DR   GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB.
DR   GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:RGD.
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:0046069; P:cGMP catabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:RGD.
DR   GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IDA:RGD.
DR   GO; GO:0043949; P:regulation of cAMP-mediated signaling; ISO:RGD.
DR   GO; GO:0010738; P:regulation of protein kinase A signaling; ISO:RGD.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 1.10.1300.10; -; 1.
DR   Gene3D; 3.30.450.40; -; 2.
DR   InterPro; IPR003018; GAF.
DR   InterPro; IPR029016; GAF-like_dom_sf.
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; PF01590; GAF; 2.
DR   Pfam; PF00233; PDEase_I; 1.
DR   PRINTS; PR00387; PDIESTERASE1.
DR   SMART; SM00065; GAF; 2.
DR   SMART; SM00471; HDc; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Allosteric enzyme; Alternative splicing; cAMP; cAMP-binding;
KW   cGMP; cGMP-binding; Cytoplasm; Hydrolase; Metal-binding;
KW   Nucleotide-binding; Reference proteome; Repeat.
FT   CHAIN           1..794
FT                   /note="cAMP and cAMP-inhibited cGMP 3',5'-cyclic
FT                   phosphodiesterase 10A"
FT                   /id="PRO_0000355559"
FT   DOMAIN          452..769
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          296..297
FT                   /note="3',5'-cAMP binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y233"
FT   REGION          340..341
FT                   /note="3',5'-cAMP binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y233"
FT   ACT_SITE        525
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   METAL           529
FT                   /note="Divalent metal cation 1"
FT   METAL           563
FT                   /note="Divalent metal cation 1"
FT   METAL           564
FT                   /note="Divalent metal cation 1"
FT   METAL           564
FT                   /note="Divalent metal cation 2"
FT   METAL           674
FT                   /note="Divalent metal cation 1"
FT   BINDING         374
FT                   /note="3',5'-cAMP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y233"
FT   BINDING         393
FT                   /note="3',5'-cAMP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y233"
FT   BINDING         525
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         726
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..141
FT                   /note="Missing (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:14752115"
FT                   /id="VSP_035919"
FT   VAR_SEQ         1..80
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:14752115"
FT                   /id="VSP_035920"
FT   VAR_SEQ         1..23
FT                   /note="MEDGPSNNASCFRRLTECFLSPS -> MSNDSPEGAVGSCNATG (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10583409,
FT                   ECO:0000303|PubMed:14752115"
FT                   /id="VSP_035921"
FT   VAR_SEQ         1..23
FT                   /note="MEDGPSNNASCFRRLTECFLSPS -> MSKKRKALEGGGGGGEPQLPEEEPT
FT                   AWFGGSSEEPAGCLPITFKGGSKGPALLALRNRTDSRGQMSNDSPEGAVGSCNATG
FT                   (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14752115"
FT                   /id="VSP_035922"
FT   VAR_SEQ         1..23
FT                   /note="MEDGPSNNASCFRRLTECFLSPS -> MSKKRKALEGGGGGGEPQLPEEEPT
FT                   AWFGGSSEEPAGCLPITFKGGSKGPALLALRNRTDSRGQMSNDSPEGAVGSCNATGSTG
FT                   STGELGKEFHTPPRRKSASDSRLALCMG (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14752115"
FT                   /id="VSP_035923"
FT   HELIX           466..471
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           483..485
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           486..498
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           500..502
FT                   /evidence="ECO:0007829|PDB:3HQW"
FT   HELIX           505..517
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   STRAND          523..526
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           527..542
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   TURN            545..547
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           550..562
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   TURN            563..566
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           572..578
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           581..585
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   STRAND          587..589
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           590..603
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   TURN            610..613
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           616..632
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           635..650
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           659..674
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           676..679
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           682..705
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           712..714
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           716..721
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           722..732
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           734..744
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           746..748
FT                   /evidence="ECO:0007829|PDB:3HR1"
FT   HELIX           749..766
FT                   /evidence="ECO:0007829|PDB:3HR1"
SQ   SEQUENCE   794 AA;  90161 MW;  A36C4678B385846E CRC64;
     MEDGPSNNAS CFRRLTECFL SPSLTDEKVK AYLSLHPQVL DEFVSESVSA ETVEKWLKRK
     NNKAEDEPSP KEVSRYQDTN MQGVVYELNS YIEQRLDTGG DNHLLLYELS SIIRIATKAD
     GFALYFLGEC NNSLCVFTPP GMKEGQPRLI PAGPITQGTT ISAYVAKSRK TLLVEDILGD
     ERFPRGTGLE SGTRIQSVLC LPIVTAIGDL IGILELYRHW GKEAFCLSHQ EVATANLAWA
     SVAIHQVQVC RGLAKQTELN DFLLDVSKTY FDNIVAIDSL LEHIMIYAKN LVNADRCALF
     QVDHKNKELY SDLFDIGEEK EGKPVFKKTK EIRFSIEKGI AGQVARTGEV LNIPDAYADP
     RFNREVDLYT GYTTRNILCM PIVSRGSVIG VVQMVNKISG SAFSKTDENN FKMFAVFCAL
     ALHCANMYHR IRHSECIYRV TMEKLSYHSI CTSEEWQGLM HFNLPARICR DIELFHFDIG
     PFENMWPGIF VYMIHRSCGT SCFELEKLCR FIMSVKKNYR RVPYHNWKHA VTVAHCMYAI
     LQNNNGLFTD LERKGLLIAC LCHDLDHRGF SNSYLQKFDH PLAALYSTST MEQHHFSQTV
     SILQLEGHNI FSTLSSSEYE QVLEIIRKAI IATDLALYFG NRKQLEEMYQ TGSLNLHNQS
     HRDRVIGLMM TACDLCSVTK LWPVTKLTAN DIYAEFWAEG DEMKKLGIQP IPMMDRDKRD
     EVPQGQLGFY NAVAIPCYTT LTQILPPTEP LLKACRDNLN QWEKVIRGEE TAMWISGPAT
     SKSTSEKPTR KVDD
//
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