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Q8CA95

- PDE10_MOUSE

UniProt

Q8CA95 - PDE10_MOUSE

Protein

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Gene

Pde10a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 2 (16 Dec 2008)
      Previous versions | rss
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    Functioni

    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.1 Publication

    Catalytic activityi

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

    Cofactori

    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.By similarity

    Kineticsi

    1. KM=0.05 µM for cAMP1 Publication
    2. KM=3 µM for cGMP1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei368 – 3681Allosteric effectorBy similarity
    Binding sitei387 – 3871Allosteric effectorBy similarity
    Active sitei519 – 5191Proton donorBy similarity
    Binding sitei519 – 5191SubstrateBy similarity
    Metal bindingi523 – 5231Divalent metal cation 1By similarity
    Metal bindingi557 – 5571Divalent metal cation 1By similarity
    Metal bindingi558 – 5581Divalent metal cation 1By similarity
    Metal bindingi558 – 5581Divalent metal cation 2By similarity
    Metal bindingi668 – 6681Divalent metal cation 1By similarity
    Binding sitei720 – 7201SubstrateBy similarity

    GO - Molecular functioni

    1. 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC
    2. 3',5'-cyclic-nucleotide phosphodiesterase activity Source: MGI
    3. cAMP binding Source: UniProtKB
    4. cGMP binding Source: UniProtKB-KW
    5. cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
    6. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. cAMP catabolic process Source: UniProtKB-UniPathway
    2. cGMP catabolic process Source: UniProtKB-UniPathway
    3. regulation of cAMP-mediated signaling Source: MGI
    4. regulation of protein kinase A signaling Source: MGI
    5. signal transduction Source: InterPro

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, cAMP-binding, cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    UniPathwayiUPA00762; UER00747.
    UPA00763; UER00748.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (EC:3.1.4.17, EC:3.1.4.35)
    Gene namesi
    Name:Pde10a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:1345143. Pde10a.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 790790cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10APRO_0000355558Add
    BLAST

    Proteomic databases

    PaxDbiQ8CA95.
    PRIDEiQ8CA95.

    PTM databases

    PhosphoSiteiQ8CA95.

    Expressioni

    Tissue specificityi

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

    Inductioni

    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.1 Publication

    Gene expression databases

    BgeeiQ8CA95.
    GenevestigatoriQ8CA95.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi204836. 3 interactions.
    IntActiQ8CA95. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CA95.
    SMRiQ8CA95. Positions 159-761.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni290 – 2912Allosteric effector bindingBy similarity
    Regioni334 – 3352Allosteric effector bindingBy similarity

    Domaini

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

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG270709.
    GeneTreeiENSGT00750000117253.
    HOGENOMiHOG000007068.
    HOVERGENiHBG082113.
    InParanoidiQ3TLU6.
    KOiK01120.
    OMAiCRFTMSV.
    OrthoDBiEOG7WQ7RN.
    TreeFamiTF316499.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    3.30.450.40. 2 hits.
    InterProiIPR003018. GAF.
    IPR029016. GAF_dom_like.
    IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF01590. GAF. 2 hits.
    PF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00065. GAF. 2 hits.
    SM00471. HDc. 1 hit.
    [Graphical view]
    SUPFAMiSSF55781. SSF55781. 2 hits.
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8CA95-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSNDSTEGTV GSCNATGLTD EKVKAYLSLH PQVLDEFVSE SVSAETVEKW    50
    LKRKTNKAKD EPSPKEVSRY QDTNMQGVVY ELNSYIEQRL DTGGDNHLLL 100
    YELSSIIRIA TKADGFALYF LGECNNSLCV FIPPGMKEGQ PRLIPAGPIT 150
    QGTTISAYVA KSRKTLLVED ILGDERFPRG TGLESGTRIQ SVLCLPIVTA 200
    IGDLIGILEL YRHWGKEAFC LSHQEVATAN LAWASVAIHQ VQVCRGLAKQ 250
    TELNDFLLDV SKTYFDNIVA IDSLLEHIMI YAKNLVNADR CALFQVDHKN 300
    KELYSDLFDI GEEKEGKPIF KKTKEIRFSI EKGIAGQVAR TGEVLNIPDA 350
    YADPRFNREV DLYTGYTTRN ILCMPIVSRG SVIGVVQMVN KISGSAFSKT 400
    DENNFKMFAV FCALALHCAN MYHRIRHSEC IYRVTMEKLS YHSICTSEEW 450
    QGLMRFNLPA RICRDIELFH FDIGPFENMW PGIFVYMIHR SCGTSCFELE 500
    KLCRFIMSVK KNYRRVPYHN WKHAVTVAHC MYAILQNNNG LFTDLERKGL 550
    LIACLCHDLD HRGFSNSYLQ KFDHPLAALY STSTMEQHHF SQTVSILQLE 600
    GHNIFSTLSS SEYEQVLEII RKAIIATDLA LYFGNRKQLE EMYQTGSLNL 650
    HNQSHRDRVI GLMMTACDLC SVTKLWPVTK LTANDIYAEF WAEGDEMKKL 700
    GIQPIPMMDR DKRDEVPQGQ LGFYNAVAIP CYTTLTQILP PTEPLLKACR 750
    DNLNQWEKVI RGEETAMWIS GPGPAPSKST PEKLNVKVED 790
    Length:790
    Mass (Da):89,408
    Last modified:December 16, 2008 - v2
    Checksum:i1B1D8111A5AD7B92
    GO
    Isoform 2 (identifier: Q8CA95-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-16: MSNDSTEGTVGSCNAT → MEKLY

    Show »
    Length:779
    Mass (Da):88,517
    Checksum:i83691B72F0D0EEAB
    GO
    Isoform 3 (identifier: Q8CA95-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-17: MSNDSTEGTVGSCNATG → MEDGPSNNASCFRRLTECFLSPS

    Show »
    Length:796
    Mass (Da):90,339
    Checksum:i4662D791B45E9EBA
    GO
    Isoform 4 (identifier: Q8CA95-4) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:727
    Mass (Da):82,409
    Checksum:i703F98A68850E67E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti774 – 7741P → Q in BAC30292. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6060Missing in isoform 4. 1 PublicationVSP_035915Add
    BLAST
    Alternative sequencei1 – 1717MSNDS…CNATG → MEDGPSNNASCFRRLTECFL SPS in isoform 3. 1 PublicationVSP_035916Add
    BLAST
    Alternative sequencei1 – 1616MSNDS…SCNAT → MEKLY in isoform 2. 1 PublicationVSP_035917Add
    BLAST
    Alternative sequencei61 – 699EPSPKEVSR → MPGPGQ in isoform 4. 1 PublicationVSP_035918

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS28384.1. [Q8CA95-3]
    RefSeqiNP_001277636.1. NM_001290707.1.
    NP_035996.2. NM_011866.2. [Q8CA95-3]
    XP_006523385.1. XM_006523322.1. [Q8CA95-2]
    UniGeneiMm.87161.

    Genome annotation databases

    EnsembliENSMUST00000089085; ENSMUSP00000086485; ENSMUSG00000023868. [Q8CA95-3]
    ENSMUST00000115720; ENSMUSP00000111385; ENSMUSG00000023868. [Q8CA95-2]
    ENSMUST00000115724; ENSMUSP00000111389; ENSMUSG00000023868. [Q8CA95-1]
    ENSMUST00000149440; ENSMUSP00000123216; ENSMUSG00000023868. [Q8CA95-4]
    GeneIDi23984.
    KEGGimmu:23984.
    UCSCiuc008ajr.1. mouse. [Q8CA95-1]
    uc008ajs.1. mouse. [Q8CA95-3]
    uc008aju.1. mouse. [Q8CA95-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS28384.1. [Q8CA95-3 ]
    RefSeqi NP_001277636.1. NM_001290707.1.
    NP_035996.2. NM_011866.2. [Q8CA95-3 ]
    XP_006523385.1. XM_006523322.1. [Q8CA95-2 ]
    UniGenei Mm.87161.

    3D structure databases

    ProteinModelPortali Q8CA95.
    SMRi Q8CA95. Positions 159-761.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204836. 3 interactions.
    IntActi Q8CA95. 1 interaction.

    Chemistry

    ChEMBLi CHEMBL1795126.

    PTM databases

    PhosphoSitei Q8CA95.

    Proteomic databases

    PaxDbi Q8CA95.
    PRIDEi Q8CA95.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000089085 ; ENSMUSP00000086485 ; ENSMUSG00000023868 . [Q8CA95-3 ]
    ENSMUST00000115720 ; ENSMUSP00000111385 ; ENSMUSG00000023868 . [Q8CA95-2 ]
    ENSMUST00000115724 ; ENSMUSP00000111389 ; ENSMUSG00000023868 . [Q8CA95-1 ]
    ENSMUST00000149440 ; ENSMUSP00000123216 ; ENSMUSG00000023868 . [Q8CA95-4 ]
    GeneIDi 23984.
    KEGGi mmu:23984.
    UCSCi uc008ajr.1. mouse. [Q8CA95-1 ]
    uc008ajs.1. mouse. [Q8CA95-3 ]
    uc008aju.1. mouse. [Q8CA95-2 ]

    Organism-specific databases

    CTDi 10846.
    MGIi MGI:1345143. Pde10a.

    Phylogenomic databases

    eggNOGi NOG270709.
    GeneTreei ENSGT00750000117253.
    HOGENOMi HOG000007068.
    HOVERGENi HBG082113.
    InParanoidi Q3TLU6.
    KOi K01120.
    OMAi CRFTMSV.
    OrthoDBi EOG7WQ7RN.
    TreeFami TF316499.

    Enzyme and pathway databases

    UniPathwayi UPA00762 ; UER00747 .
    UPA00763 ; UER00748 .

    Miscellaneous databases

    ChiTaRSi PDE10A. mouse.
    NextBioi 303873.
    PROi Q8CA95.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8CA95.
    Genevestigatori Q8CA95.

    Family and domain databases

    Gene3Di 1.10.1300.10. 1 hit.
    3.30.450.40. 2 hits.
    InterProi IPR003018. GAF.
    IPR029016. GAF_dom_like.
    IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view ]
    Pfami PF01590. GAF. 2 hits.
    PF00233. PDEase_I. 1 hit.
    [Graphical view ]
    PRINTSi PR00387. PDIESTERASE1.
    SMARTi SM00065. GAF. 2 hits.
    SM00471. HDc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55781. SSF55781. 2 hits.
    PROSITEi PS00126. PDEASE_I. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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).

    Entry informationi

    Entry nameiPDE10_MOUSE
    AccessioniPrimary (citable) accession number: Q8CA95
    Secondary accession number(s): Q3TLU6
    , Q3TRG6, Q69C21, Q9WVI1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 16, 2008
    Last sequence update: December 16, 2008
    Last modified: October 1, 2014
    This is version 86 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3