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Q8CA95 (PDE10_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 85. 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length790 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. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. Ref.1

Catalytic activity

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

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

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 By similarity.

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 By similarity.

Tissue specificity

Detected in striatum (at protein level). Detected in testis and brain. Ref.1 Ref.2

Induction

Down-regulated by the expression of a huntingtin (HD) gene with an expanded polyglutamine repeat prior to the onset of neurological symptoms related to Huntington disease. Ref.2

Domain

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

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 By similarity.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.05 µM for cAMP Ref.1

KM=3 µM for cGMP

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8CA95-1)

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: Q8CA95-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MSNDSTEGTVGSCNAT → MEKLY
Isoform 3 (identifier: Q8CA95-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MSNDSTEGTVGSCNATG → MEDGPSNNASCFRRLTECFLSPS
Isoform 4 (identifier: Q8CA95-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.
     61-69: EPSPKEVSR → MPGPGQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 790790cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
PRO_0000355558

Regions

Region290 – 2912Allosteric effector binding By similarity
Region334 – 3352Allosteric effector binding By similarity

Sites

Active site5191Proton donor By similarity
Metal binding5231Divalent metal cation 1 By similarity
Metal binding5571Divalent metal cation 1 By similarity
Metal binding5581Divalent metal cation 1 By similarity
Metal binding5581Divalent metal cation 2 By similarity
Metal binding6681Divalent metal cation 1 By similarity
Binding site3681Allosteric effector By similarity
Binding site3871Allosteric effector By similarity
Binding site5191Substrate By similarity
Binding site7201Substrate By similarity

Natural variations

Alternative sequence1 – 6060Missing in isoform 4.
VSP_035915
Alternative sequence1 – 1717MSNDS…CNATG → MEDGPSNNASCFRRLTECFL SPS in isoform 3.
VSP_035916
Alternative sequence1 – 1616MSNDS…SCNAT → MEKLY in isoform 2.
VSP_035917
Alternative sequence61 – 699EPSPKEVSR → MPGPGQ in isoform 4.
VSP_035918

Experimental info

Sequence conflict7741P → Q in BAC30292. Ref.3

Sequences

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

Last modified December 16, 2008. Version 2.
Checksum: 1B1D8111A5AD7B92

FASTA79089,408
        10         20         30         40         50         60 
MSNDSTEGTV GSCNATGLTD EKVKAYLSLH PQVLDEFVSE SVSAETVEKW LKRKTNKAKD 

        70         80         90        100        110        120 
EPSPKEVSRY QDTNMQGVVY ELNSYIEQRL DTGGDNHLLL YELSSIIRIA TKADGFALYF 

       130        140        150        160        170        180 
LGECNNSLCV FIPPGMKEGQ PRLIPAGPIT QGTTISAYVA KSRKTLLVED ILGDERFPRG 

       190        200        210        220        230        240 
TGLESGTRIQ SVLCLPIVTA IGDLIGILEL YRHWGKEAFC LSHQEVATAN LAWASVAIHQ 

       250        260        270        280        290        300 
VQVCRGLAKQ TELNDFLLDV SKTYFDNIVA IDSLLEHIMI YAKNLVNADR CALFQVDHKN 

       310        320        330        340        350        360 
KELYSDLFDI GEEKEGKPIF KKTKEIRFSI EKGIAGQVAR TGEVLNIPDA YADPRFNREV 

       370        380        390        400        410        420 
DLYTGYTTRN ILCMPIVSRG SVIGVVQMVN KISGSAFSKT DENNFKMFAV FCALALHCAN 

       430        440        450        460        470        480 
MYHRIRHSEC IYRVTMEKLS YHSICTSEEW QGLMRFNLPA RICRDIELFH FDIGPFENMW 

       490        500        510        520        530        540 
PGIFVYMIHR SCGTSCFELE KLCRFIMSVK KNYRRVPYHN WKHAVTVAHC MYAILQNNNG 

       550        560        570        580        590        600 
LFTDLERKGL LIACLCHDLD HRGFSNSYLQ KFDHPLAALY STSTMEQHHF SQTVSILQLE 

       610        620        630        640        650        660 
GHNIFSTLSS SEYEQVLEII RKAIIATDLA LYFGNRKQLE EMYQTGSLNL HNQSHRDRVI 

       670        680        690        700        710        720 
GLMMTACDLC SVTKLWPVTK LTANDIYAEF WAEGDEMKKL GIQPIPMMDR DKRDEVPQGQ 

       730        740        750        760        770        780 
LGFYNAVAIP CYTTLTQILP PTEPLLKACR DNLNQWEKVI RGEETAMWIS GPGPAPSKST 

       790 
PEKLNVKVED 

« Hide

Isoform 2 [UniParc].

Checksum: 83691B72F0D0EEAB
Show »

FASTA77988,517
Isoform 3 [UniParc].

Checksum: 4662D791B45E9EBA
Show »

FASTA79690,339
Isoform 4 [UniParc].

Checksum: 703F98A68850E67E
Show »

FASTA72782,409

References

« Hide 'large scale' references
[1]"Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A."
Soderling S.H., Bayuga S.J., Beavo J.A.
Proc. Natl. Acad. Sci. U.S.A. 96:7071-7076(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms."
Hebb A.L., Robertson H.A., Denovan-Wright E.M.
Neuroscience 123:967-981(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INDUCTION, TISSUE SPECIFICITY.
Strain: C57BL/6 X CBA.
Tissue: Corpus striatum.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
Strain: C57BL/6J.
Tissue: Mammary gland, Spinal cord and Thymus.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF110507 mRNA. Translation: AAD31544.1.
AY360383 mRNA. Translation: AAR12579.1.
AK039249 mRNA. Translation: BAC30292.1.
AK162804 mRNA. Translation: BAE37063.1.
AK166310 mRNA. Translation: BAE38696.1.
CH466619 Genomic DNA. Translation: EDL02097.1.
CH466619 Genomic DNA. Translation: EDL02099.1.
BC113201 mRNA. Translation: AAI13202.1.
CCDSCCDS28384.1. [Q8CA95-3]
RefSeqNP_001277636.1. NM_001290707.1.
NP_035996.2. NM_011866.2. [Q8CA95-3]
XP_006523385.1. XM_006523322.1. [Q8CA95-2]
UniGeneMm.87161.

3D structure databases

ProteinModelPortalQ8CA95.
SMRQ8CA95. Positions 159-761.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204836. 3 interactions.
IntActQ8CA95. 1 interaction.

Chemistry

ChEMBLCHEMBL1795126.

PTM databases

PhosphoSiteQ8CA95.

Proteomic databases

PaxDbQ8CA95.
PRIDEQ8CA95.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000089085; ENSMUSP00000086485; ENSMUSG00000023868. [Q8CA95-3]
ENSMUST00000115720; ENSMUSP00000111385; ENSMUSG00000023868. [Q8CA95-2]
ENSMUST00000115724; ENSMUSP00000111389; ENSMUSG00000023868. [Q8CA95-1]
ENSMUST00000149440; ENSMUSP00000123216; ENSMUSG00000023868. [Q8CA95-4]
GeneID23984.
KEGGmmu:23984.
UCSCuc008ajr.1. mouse. [Q8CA95-1]
uc008ajs.1. mouse. [Q8CA95-3]
uc008aju.1. mouse. [Q8CA95-2]

Organism-specific databases

CTD10846.
MGIMGI:1345143. Pde10a.

Phylogenomic databases

eggNOGNOG270709.
GeneTreeENSGT00750000117253.
HOGENOMHOG000007068.
HOVERGENHBG082113.
InParanoidQ3TLU6.
KOK01120.
OMACRFTMSV.
OrthoDBEOG7WQ7RN.
TreeFamTF316499.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.
UPA00763; UER00748.

Gene expression databases

BgeeQ8CA95.
GenevestigatorQ8CA95.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProIPR003018. GAF.
IPR029016. GAF_dom_like.
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]
SUPFAMSSF55781. SSF55781. 2 hits.
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDE10A. mouse.
NextBio303873.
PROQ8CA95.
SOURCESearch...

Entry information

Entry namePDE10_MOUSE
AccessionPrimary (citable) accession number: Q8CA95
Secondary accession number(s): Q3TLU6 expand/collapse secondary AC list , Q3TRG6, Q69C21, Q9WVI1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: December 16, 2008
Last modified: July 9, 2014
This is version 85 of the entry and version 2 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot