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Protein

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

Gene

Pde10a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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.2 Publications

Catalytic activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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

Kineticsi

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

    Pathwayi: 3',5'-cyclic AMP degradation

    This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
    Proteins known to be involved in this subpathway in this organism are:
    1. cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (Pde8b), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (Pde8a), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (Pde7b)
    This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

    Pathwayi: 3',5'-cyclic GMP degradation

    This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
    Proteins known to be involved in this subpathway in this organism are:
    1. cGMP-specific 3',5'-cyclic phosphodiesterase (Pde5a), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (Pde9a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a)
    This subpathway is part of the pathway 3',5'-cyclic GMP degradation, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP degradation and in Purine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei368Allosteric effectorBy similarity1
    Binding sitei387Allosteric effectorBy similarity1
    Active sitei519Proton donorBy similarity1
    Binding sitei519SubstrateBy similarity1
    Metal bindingi523Divalent metal cation 1By similarity1
    Metal bindingi557Divalent metal cation 1By similarity1
    Metal bindingi558Divalent metal cation 1By similarity1
    Metal bindingi558Divalent metal cation 2By similarity1
    Metal bindingi668Divalent metal cation 1By similarity1
    Binding sitei720SubstrateBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • cAMP catabolic process Source: UniProtKB-UniPathway
    • cGMP catabolic process Source: UniProtKB-UniPathway
    • regulation of cAMP-mediated signaling Source: MGI
    • regulation of protein kinase A signaling Source: MGI
    • signal transduction Source: InterPro

    Keywordsi

    Molecular functionAllosteric enzyme, Hydrolase
    LigandcAMP, cAMP-binding, cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-418457 cGMP effects
    R-MMU-418555 G alpha (s) signalling events
    SABIO-RKiQ8CA95
    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 17

    Organism-specific databases

    MGIiMGI:1345143 Pde10a

    Subcellular locationi

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi101Y → C: Decreased protein abundance; decreased 3',5'-cyclic-nucleotide phosphodiesterase activity. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL1795126

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003555581 – 790cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AAdd BLAST790

    Proteomic databases

    PaxDbiQ8CA95
    PeptideAtlasiQ8CA95
    PRIDEiQ8CA95

    PTM databases

    iPTMnetiQ8CA95
    PhosphoSitePlusiQ8CA95
    SwissPalmiQ8CA95

    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

    BgeeiENSMUSG00000023868
    ExpressionAtlasiQ8CA95 baseline and differential
    GenevisibleiQ8CA95 MM

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi204836, 3 interactors
    IntActiQ8CA95, 1 interactor
    STRINGi10090.ENSMUSP00000086485

    Chemistry databases

    BindingDBiQ8CA95

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CA95
    SMRiQ8CA95
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini446 – 763PDEasePROSITE-ProRule annotationAdd BLAST318

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni290 – 291Allosteric effector bindingBy similarity2
    Regioni334 – 335Allosteric effector bindingBy similarity2

    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

    eggNOGiKOG3689 Eukaryota
    ENOG410XRI7 LUCA
    GeneTreeiENSGT00760000119066
    HOGENOMiHOG000007068
    HOVERGENiHBG082113
    InParanoidiQ8CA95
    KOiK18438
    OMAiLKACRNN
    OrthoDBiEOG091G037C
    TreeFamiTF316499

    Family and domain databases

    CDDicd00077 HDc, 1 hit
    Gene3Di1.10.1300.10, 1 hit
    3.30.450.40, 2 hits
    InterProiView protein in InterPro
    IPR003018 GAF
    IPR029016 GAF-like_dom_sf
    IPR003607 HD/PDEase_dom
    IPR023088 PDEase
    IPR002073 PDEase_catalytic_dom
    IPR036971 PDEase_catalytic_dom_sf
    IPR023174 PDEase_CS
    PfamiView protein in Pfam
    PF01590 GAF, 2 hits
    PF00233 PDEase_I, 1 hit
    PRINTSiPR00387 PDIESTERASE1
    SMARTiView protein in SMART
    SM00065 GAF, 2 hits
    SM00471 HDc, 1 hit
    PROSITEiView protein in PROSITE
    PS00126 PDEASE_I_1, 1 hit
    PS51845 PDEASE_I_2, 1 hit

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    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

            10         20         30         40         50
    MSNDSTEGTV GSCNATGLTD EKVKAYLSLH PQVLDEFVSE SVSAETVEKW
    60 70 80 90 100
    LKRKTNKAKD EPSPKEVSRY QDTNMQGVVY ELNSYIEQRL DTGGDNHLLL
    110 120 130 140 150
    YELSSIIRIA TKADGFALYF LGECNNSLCV FIPPGMKEGQ PRLIPAGPIT
    160 170 180 190 200
    QGTTISAYVA KSRKTLLVED ILGDERFPRG TGLESGTRIQ SVLCLPIVTA
    210 220 230 240 250
    IGDLIGILEL YRHWGKEAFC LSHQEVATAN LAWASVAIHQ VQVCRGLAKQ
    260 270 280 290 300
    TELNDFLLDV SKTYFDNIVA IDSLLEHIMI YAKNLVNADR CALFQVDHKN
    310 320 330 340 350
    KELYSDLFDI GEEKEGKPIF KKTKEIRFSI EKGIAGQVAR TGEVLNIPDA
    360 370 380 390 400
    YADPRFNREV DLYTGYTTRN ILCMPIVSRG SVIGVVQMVN KISGSAFSKT
    410 420 430 440 450
    DENNFKMFAV FCALALHCAN MYHRIRHSEC IYRVTMEKLS YHSICTSEEW
    460 470 480 490 500
    QGLMRFNLPA RICRDIELFH FDIGPFENMW PGIFVYMIHR SCGTSCFELE
    510 520 530 540 550
    KLCRFIMSVK KNYRRVPYHN WKHAVTVAHC MYAILQNNNG LFTDLERKGL
    560 570 580 590 600
    LIACLCHDLD HRGFSNSYLQ KFDHPLAALY STSTMEQHHF SQTVSILQLE
    610 620 630 640 650
    GHNIFSTLSS SEYEQVLEII RKAIIATDLA LYFGNRKQLE EMYQTGSLNL
    660 670 680 690 700
    HNQSHRDRVI GLMMTACDLC SVTKLWPVTK LTANDIYAEF WAEGDEMKKL
    710 720 730 740 750
    GIQPIPMMDR DKRDEVPQGQ LGFYNAVAIP CYTTLTQILP PTEPLLKACR
    760 770 780 790
    DNLNQWEKVI RGEETAMWIS GPGPAPSKST PEKLNVKVED
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti774P → Q in BAC30292 (PubMed:16141072).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0359151 – 60Missing in isoform 4. 1 PublicationAdd BLAST60
    Alternative sequenceiVSP_0359161 – 17MSNDS…CNATG → MEDGPSNNASCFRRLTECFL SPS in isoform 3. 1 PublicationAdd BLAST17
    Alternative sequenceiVSP_0359171 – 16MSNDS…SCNAT → MEKLY in isoform 2. 1 PublicationAdd BLAST16
    Alternative sequenceiVSP_03591861 – 69EPSPKEVSR → MPGPGQ in isoform 4. 1 Publication9

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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]
    CCDS84274.1 [Q8CA95-2]
    RefSeqiNP_001277636.1, NM_001290707.1
    NP_001334250.1, NM_001347321.1 [Q8CA95-2]
    NP_035996.2, NM_011866.2 [Q8CA95-3]
    XP_017172950.1, XM_017317461.1 [Q8CA95-1]
    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

    Similar proteinsi

    Entry informationi

    Entry nameiPDE10_MOUSE
    AccessioniPrimary (citable) accession number: Q8CA95
    Secondary accession number(s): Q3TLU6
    , Q3TRG6, Q69C21, Q9WVI1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 16, 2008
    Last sequence update: December 16, 2008
    Last modified: March 28, 2018
    This is version 112 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health