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Q9QYJ6 (PDE10_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

EC=3.1.4.17
EC=3.1.4.35
Gene names
Name:Pde10a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length794 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. Ref.1

Catalytic activity

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate. Ref.2

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate. Ref.2

Cofactor

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.

Enzyme regulation

Inhibited by dipyridamole and moderately by IBMX, zaprinast and rolipram. Ref.1

Pathway

Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.

Subunit structure

Homodimer By similarity.

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Detected in striatum and testis (at protein level). Detected in whole brain, hippocampus, olfactory bulb, striatum neurons and testis. Ref.1 Ref.2

Induction

Up-regulated in brain after seizures. Up-regulated in the hippocampus one hour after induction of long-term potentiation. Ref.1 Ref.2

Domain

The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.

Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.26 µM for cAMP Ref.1

KM=9.3 µM for cGMP

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QYJ6-1)

Also known as: PDE10A2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9QYJ6-2)

Also known as: PDE10A3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MEDGPSNNASCFRRLTECFLSPS → MSNDSPEGAVGSCNATG
Isoform 3 (identifier: Q9QYJ6-3)

Also known as: PDE10A11;

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MEDGPSNNASCFRRLTECFLSPS → MSKKRKALEG...GAVGSCNATG
Isoform 4 (identifier: Q9QYJ6-4)

Also known as: PDE10A12;

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MEDGPSNNASCFRRLTECFLSPS → MSKKRKALEG...SDSRLALCMG
Isoform 5 (identifier: Q9QYJ6-5)

Also known as: PDE10A13;

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: Missing.
Isoform 6 (identifier: Q9QYJ6-6)

Also known as: PDE10A14;

The sequence of this isoform differs from the canonical sequence as follows:
     1-141: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 794794cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
PRO_0000355559

Regions

Region296 – 2972Allosteric effector binding By similarity
Region340 – 3412Allosteric effector binding By similarity

Sites

Active site5251Proton donor By similarity
Metal binding5291Divalent metal cation 1
Metal binding5631Divalent metal cation 1
Metal binding5641Divalent metal cation 1
Metal binding5641Divalent metal cation 2
Metal binding6741Divalent metal cation 1
Binding site3741Allosteric effector By similarity
Binding site3931Allosteric effector By similarity
Binding site5251Substrate By similarity
Binding site7261Substrate By similarity

Natural variations

Alternative sequence1 – 141141Missing in isoform 6.
VSP_035919
Alternative sequence1 – 8080Missing in isoform 5.
VSP_035920
Alternative sequence1 – 2323MEDGP…FLSPS → MSNDSPEGAVGSCNATG in isoform 2.
VSP_035921
Alternative sequence1 – 2323MEDGP…FLSPS → MSKKRKALEGGGGGGEPQLP EEEPTAWFGGSSEEPAGCLP ITFKGGSKGPALLALRNRTD SRGQMSNDSPEGAVGSCNAT G in isoform 3.
VSP_035922
Alternative sequence1 – 2323MEDGP…FLSPS → MSKKRKALEGGGGGGEPQLP EEEPTAWFGGSSEEPAGCLP ITFKGGSKGPALLALRNRTD SRGQMSNDSPEGAVGSCNAT GSTGSTGELGKEFHTPPRRK SASDSRLALCMG in isoform 4.
VSP_035923

Secondary structure

............................................... 794
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE10A2) [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: A36C4678B385846E

FASTA79490,161
        10         20         30         40         50         60 
MEDGPSNNAS CFRRLTECFL SPSLTDEKVK AYLSLHPQVL DEFVSESVSA ETVEKWLKRK 

        70         80         90        100        110        120 
NNKAEDEPSP KEVSRYQDTN MQGVVYELNS YIEQRLDTGG DNHLLLYELS SIIRIATKAD 

       130        140        150        160        170        180 
GFALYFLGEC NNSLCVFTPP GMKEGQPRLI PAGPITQGTT ISAYVAKSRK TLLVEDILGD 

       190        200        210        220        230        240 
ERFPRGTGLE SGTRIQSVLC LPIVTAIGDL IGILELYRHW GKEAFCLSHQ EVATANLAWA 

       250        260        270        280        290        300 
SVAIHQVQVC RGLAKQTELN DFLLDVSKTY FDNIVAIDSL LEHIMIYAKN LVNADRCALF 

       310        320        330        340        350        360 
QVDHKNKELY SDLFDIGEEK EGKPVFKKTK EIRFSIEKGI AGQVARTGEV LNIPDAYADP 

       370        380        390        400        410        420 
RFNREVDLYT GYTTRNILCM PIVSRGSVIG VVQMVNKISG SAFSKTDENN FKMFAVFCAL 

       430        440        450        460        470        480 
ALHCANMYHR IRHSECIYRV TMEKLSYHSI CTSEEWQGLM HFNLPARICR DIELFHFDIG 

       490        500        510        520        530        540 
PFENMWPGIF VYMIHRSCGT SCFELEKLCR FIMSVKKNYR RVPYHNWKHA VTVAHCMYAI 

       550        560        570        580        590        600 
LQNNNGLFTD LERKGLLIAC LCHDLDHRGF SNSYLQKFDH PLAALYSTST MEQHHFSQTV 

       610        620        630        640        650        660 
SILQLEGHNI FSTLSSSEYE QVLEIIRKAI IATDLALYFG NRKQLEEMYQ TGSLNLHNQS 

       670        680        690        700        710        720 
HRDRVIGLMM TACDLCSVTK LWPVTKLTAN DIYAEFWAEG DEMKKLGIQP IPMMDRDKRD 

       730        740        750        760        770        780 
EVPQGQLGFY NAVAIPCYTT LTQILPPTEP LLKACRDNLN QWEKVIRGEE TAMWISGPAT 

       790 
SKSTSEKPTR KVDD 

« Hide

Isoform 2 (PDE10A3) [UniParc].

Checksum: 44F421DF1CC8FBA0
Show »

FASTA78889,196
Isoform 3 (PDE10A11) [UniParc].

Checksum: 31F6E5D4DDB8F60B
Show »

FASTA85295,777
Isoform 4 (PDE10A12) [UniParc].

Checksum: 86527DFF337E4B4F
Show »

FASTA88399,036
Isoform 5 (PDE10A13) [UniParc].

Checksum: 5AFBCD366955F8F6
Show »

FASTA71481,028
Isoform 6 (PDE10A14) [UniParc].

Checksum: C712183FC1CFA76F
Show »

FASTA65374,275

References

« Hide 'large scale' references
[1]"Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A."
Fujishige K., Kotera J., Omori K.
Eur. J. Biochem. 266:1118-1127(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Differential amplification of intron-containing transcripts reveals long term potentiation-associated up-regulation of specific Pde10A phosphodiesterase splice variants."
O'Connor V., Genin A., Davis S., Karishma K.K., Doyere V., De Zeeuw C.I., Sanger G., Hunt S.P., Richter-Levin G., Mallet J., Laroche S., Bliss T.V.P., French P.J.
J. Biol. Chem. 279:15841-15849(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5 AND 6), TISSUE SPECIFICITY, CATALYTIC ACTIVITY, INDUCTION.
Strain: Wistar.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors."
Chappie T.A., Humphrey J.M., Allen M.P., Estep K.G., Fox C.B., Lebel L.A., Liras S., Marr E.S., Menniti F.S., Pandit J., Schmidt C.J., Tu M., Williams R.D., Yang F.V.
J. Med. Chem. 50:182-185(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 452-794 IN COMPLEXES WITH ZINC; MAGNESIUM AND A SYNTHETIC INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB027155 mRNA. Translation: BAA88996.1.
AB027156 mRNA. Translation: BAA88997.1.
AY462091 mRNA. Translation: AAS21243.1.
AY462092 mRNA. Translation: AAS21244.1.
AY462093 mRNA. Translation: AAS21245.1.
AY462094 mRNA. Translation: AAS21246.1.
AY462095 mRNA. Translation: AAS21247.1.
CH474059 Genomic DNA. Translation: EDL83106.1.
RefSeqNP_071572.1. NM_022236.1.
UniGeneRn.44869.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2O8HX-ray1.80A452-794[»]
2OVVX-ray2.00A452-794[»]
2OVYX-ray1.80A452-794[»]
3HQWX-ray1.70A452-794[»]
3HQYX-ray2.00A452-794[»]
3HQZX-ray1.70A452-794[»]
3HR1X-ray1.53A452-794[»]
3LXGX-ray2.30A463-770[»]
3QPNX-ray2.00A452-794[»]
3QPOX-ray1.80A452-794[»]
3QPPX-ray1.80A452-794[»]
ProteinModelPortalQ9QYJ6.
SMRQ9QYJ6. Positions 256-432, 464-770.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ9QYJ6.
ChEMBLCHEMBL6140.

Proteomic databases

PaxDbQ9QYJ6.
PRIDEQ9QYJ6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000043474; ENSRNOP00000042134; ENSRNOG00000011310. [Q9QYJ6-1]
GeneID63885.
KEGGrno:63885.

Organism-specific databases

CTD10846.
RGD68434. Pde10a.

Phylogenomic databases

eggNOGNOG270709.
GeneTreeENSGT00750000117253.
HOGENOMHOG000007068.
HOVERGENHBG082113.
InParanoidQ6S9E8.
KOK01120.
TreeFamTF316499.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.
UPA00763; UER00748.

Gene expression databases

GenevestigatorQ9QYJ6.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003018. GAF.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9QYJ6.
NextBio612518.
PMAP-CutDBQ9QYJ6.
PROQ9QYJ6.

Entry information

Entry namePDE10_RAT
AccessionPrimary (citable) accession number: Q9QYJ6
Secondary accession number(s): Q6S9E6 expand/collapse secondary AC list , Q6S9E7, Q6S9E8, Q6S9E9, Q9QYJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways