Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A

Gene

Pde9a

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

Functioni

Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes (PubMed:9624145). Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (PubMed:22328573, PubMed:24746365).Curated4 Publications

Catalytic activityi

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 Zn2+ ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.By similarity
  • Mg2+By similarityNote: Binds 1 Mg2+ ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.By similarity

Activity regulationi

Inhibited by SCH 51866 and moderately, by zaprinast. Specifically inhibited by PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) (PubMed:22328573).2 Publications

Kineticsi

  1. KM=0.07 mM for cGMP1 Publication

    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), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (Pde9a)
    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
    Active sitei251Proton donorBy similarity1
    Metal bindingi255Zinc; via tele nitrogenBy similarity1
    Metal bindingi291Zinc; via tele nitrogenBy similarity1
    Metal bindingi292MagnesiumBy similarity1
    Metal bindingi292ZincBy similarity1
    Binding sitei292cGMPBy similarity1
    Metal bindingi401ZincBy similarity1
    Binding sitei401cGMPBy similarity1
    Binding sitei423cGMPBy similarity1
    Binding sitei423Inhibitor specific to Pde9aBy similarity1
    Binding sitei452InhibitorBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi251 – 255cGMPBy similarity5
    Nucleotide bindingi451 – 452cGMPBy similarity2

    GO - Molecular functioni

    GO - Biological processi

    • cGMP catabolic process Source: UniProtKB
    • cGMP-mediated signaling Source: Ensembl
    • cGMP metabolic process Source: MGI
    • positive regulation of cardiac muscle hypertrophy Source: UniProtKB

    Keywordsi

    Molecular functionHydrolase
    LigandcGMP, Magnesium, Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.1.4.35 3474
    ReactomeiR-MMU-418457 cGMP effects
    UniPathwayi
    UPA00763;UER00748

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9ACurated (EC:3.1.4.351 Publication)
    Gene namesi
    Name:Pde9a
    Synonyms:Pde8b
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 17

    Organism-specific databases

    MGIiMGI:1277179 Pde9a

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice hearts develop less dilation and dysfunction when exposed to sustained pressure overload.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001988421 – 534High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AAdd BLAST534

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei318PhosphoserineBy similarity1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO70628
    PaxDbiO70628
    PRIDEiO70628

    PTM databases

    iPTMnetiO70628
    PhosphoSitePlusiO70628

    Expressioni

    Tissue specificityi

    Highly expressed in kidney. Lower levels in liver, lung and brain (PubMed:9624145). Widely expressed in brain, with highest expression in cerebellar Purkinje cells (PubMed:14501210). Present in heart (at protein level) (PubMed:25799991).3 Publications

    Gene expression databases

    BgeeiENSMUSG00000041119 Expressed in 280 organ(s), highest expression level in intestinal villus
    CleanExiMM_PDE9A
    ExpressionAtlasiO70628 baseline and differential
    GenevisibleiO70628 MM

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    GO - Molecular functioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000038005

    Structurei

    3D structure databases

    ProteinModelPortaliO70628
    SMRiO70628
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini175 – 496PDEasePROSITE-ProRule annotationAdd BLAST322

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3689 Eukaryota
    ENOG410XRI7 LUCA
    GeneTreeiENSGT00760000119066
    HOGENOMiHOG000008058
    HOVERGENiHBG053545
    InParanoidiO70628
    KOiK13761
    OrthoDBiEOG091G082I
    PhylomeDBiO70628
    TreeFamiTF314638

    Family and domain databases

    CDDicd00077 HDc, 1 hit
    Gene3Di1.10.1300.10, 1 hit
    InterProiView protein in InterPro
    IPR003607 HD/PDEase_dom
    IPR023088 PDEase
    IPR002073 PDEase_catalytic_dom
    IPR036971 PDEase_catalytic_dom_sf
    IPR023174 PDEase_CS
    PfamiView protein in Pfam
    PF00233 PDEase_I, 1 hit
    PRINTSiPR00387 PDIESTERASE1
    SMARTiView protein in SMART
    SM00471 HDc, 1 hit
    PROSITEiView protein in PROSITE
    PS00126 PDEASE_I_1, 1 hit
    PS51845 PDEASE_I_2, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket
    Note: A number of isoforms are produced.

    This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: O70628-1) [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
    MGAGSSSYRP KAIYLDIDGR IQKVVFSKYC NSSDIMDLFC IATGLPRNTT
    60 70 80 90 100
    ISLLTTDDAM VSIDPTMPAN SERTPYKVRP VAVKQVSERE ELIQGVLAQV
    110 120 130 140 150
    AEQFSRAFKI NELKAEVANH LAVLEKRVEL EGLKVVEIEK CKSDIKKMRE
    160 170 180 190 200
    ELAARNSRTN CPCKYSFLDN KKLTPRRDVP TYPKYLLSPE TIEALRKPTF
    210 220 230 240 250
    DVWLWEPNEM LSCLEHMYHD LGLVRDFSIN PITLRRWLLC VHDNYRNNPF
    260 270 280 290 300
    HNFRHCFCVT QMMYSMVWLC GLQEKFSQMD ILVLMTAAIC HDLDHPGYNN
    310 320 330 340 350
    TYQINARTEL AVRYNDISPL ENHHCAIAFQ ILARPECNIF ASVPPEGFRQ
    360 370 380 390 400
    IRQGMITLIL ATDMARHAEI MDSFKEKMEN FDYSNEEHLT LLKMILIKCC
    410 420 430 440 450
    DISNEVRPME VAEPWVDCLL EEYFMQSDRE KSEGLPVAPF MDRDKVTKAT
    460 470 480 490 500
    AQIGFIKFVL IPMFETVTKL FPVVEETMLR PLWESREHYE ELKQLDDAMK
    510 520 530
    ELQKKTESLT SGAPENTTEK NRDAKDSEGH SPPN
    Length:534
    Mass (Da):61,636
    Last modified:August 1, 1998 - v1
    Checksum:i28126C7BB7375241
    GO

    Computationally mapped potential isoform sequencesi

    There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    D3YTQ4D3YTQ4_MOUSE
    Phosphodiesterase
    Pde9a
    508Annotation score:
    F6ZAU1F6ZAU1_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    180Annotation score:
    D3Z408D3Z408_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    80Annotation score:
    D6RH57D6RH57_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    102Annotation score:
    D6RGP8D6RGP8_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    63Annotation score:
    D6RFN9D6RFN9_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    37Annotation score:
    D6REE8D6REE8_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    51Annotation score:
    F7APE3F7APE3_MOUSE
    High affinity cGMP-specific 3',5'-c...
    Pde9a
    91Annotation score:

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF031147 mRNA Translation: AAC24344.1
    AF068247 mRNA Translation: AAC23996.1
    BC061163 mRNA Translation: AAH61163.1
    CCDSiCCDS28605.1 [O70628-1]
    RefSeqiNP_001157220.1, NM_001163748.1 [O70628-1]
    NP_032830.3, NM_008804.4 [O70628-1]
    UniGeneiMm.10812

    Genome annotation databases

    EnsembliENSMUST00000047168; ENSMUSP00000038005; ENSMUSG00000041119 [O70628-1]
    ENSMUST00000127929; ENSMUSP00000117611; ENSMUSG00000041119 [O70628-1]
    GeneIDi18585
    KEGGimmu:18585
    UCSCiuc008buz.2 mouse [O70628-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF031147 mRNA Translation: AAC24344.1
    AF068247 mRNA Translation: AAC23996.1
    BC061163 mRNA Translation: AAH61163.1
    CCDSiCCDS28605.1 [O70628-1]
    RefSeqiNP_001157220.1, NM_001163748.1 [O70628-1]
    NP_032830.3, NM_008804.4 [O70628-1]
    UniGeneiMm.10812

    3D structure databases

    ProteinModelPortaliO70628
    SMRiO70628
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000038005

    PTM databases

    iPTMnetiO70628
    PhosphoSitePlusiO70628

    Proteomic databases

    MaxQBiO70628
    PaxDbiO70628
    PRIDEiO70628

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000047168; ENSMUSP00000038005; ENSMUSG00000041119 [O70628-1]
    ENSMUST00000127929; ENSMUSP00000117611; ENSMUSG00000041119 [O70628-1]
    GeneIDi18585
    KEGGimmu:18585
    UCSCiuc008buz.2 mouse [O70628-1]

    Organism-specific databases

    CTDi5152
    MGIiMGI:1277179 Pde9a

    Phylogenomic databases

    eggNOGiKOG3689 Eukaryota
    ENOG410XRI7 LUCA
    GeneTreeiENSGT00760000119066
    HOGENOMiHOG000008058
    HOVERGENiHBG053545
    InParanoidiO70628
    KOiK13761
    OrthoDBiEOG091G082I
    PhylomeDBiO70628
    TreeFamiTF314638

    Enzyme and pathway databases

    UniPathwayi
    UPA00763;UER00748

    BRENDAi3.1.4.35 3474
    ReactomeiR-MMU-418457 cGMP effects

    Miscellaneous databases

    ChiTaRSiPde9a mouse
    PROiPR:O70628
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000041119 Expressed in 280 organ(s), highest expression level in intestinal villus
    CleanExiMM_PDE9A
    ExpressionAtlasiO70628 baseline and differential
    GenevisibleiO70628 MM

    Family and domain databases

    CDDicd00077 HDc, 1 hit
    Gene3Di1.10.1300.10, 1 hit
    InterProiView protein in InterPro
    IPR003607 HD/PDEase_dom
    IPR023088 PDEase
    IPR002073 PDEase_catalytic_dom
    IPR036971 PDEase_catalytic_dom_sf
    IPR023174 PDEase_CS
    PfamiView protein in Pfam
    PF00233 PDEase_I, 1 hit
    PRINTSiPR00387 PDIESTERASE1
    SMARTiView protein in SMART
    SM00471 HDc, 1 hit
    PROSITEiView protein in PROSITE
    PS00126 PDEASE_I_1, 1 hit
    PS51845 PDEASE_I_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPDE9A_MOUSE
    AccessioniPrimary (citable) accession number: O70628
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: August 1, 1998
    Last modified: November 7, 2018
    This is version 144 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again