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O89084

- PDE4A_MOUSE

UniProt

O89084 - PDE4A_MOUSE

Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Gene

Pde4a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (01 Mar 2002)
      Previous versions | rss
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    Functioni

    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.By similarity

    Catalytic activityi

    Adenosine 3',5'-cyclic phosphate + H2O = adenosine 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

    Enzyme regulationi

    Inhibited by rolipram and diazepam.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei69 – 702Cleavage; by caspase-3By similarity
    Active sitei419 – 4191Proton donorBy similarity
    Metal bindingi423 – 4231Divalent metal cation 1By similarity
    Metal bindingi459 – 4591Divalent metal cation 1By similarity
    Metal bindingi460 – 4601Divalent metal cation 1By similarity
    Metal bindingi460 – 4601Divalent metal cation 2By similarity
    Binding sitei460 – 4601cAMPBy similarity
    Metal bindingi577 – 5771Divalent metal cation 1By similarity
    Binding sitei577 – 5771cAMPBy similarity
    Sitei580 – 5801Binds AMP, but not cAMPBy similarity
    Binding sitei628 – 6281cAMPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi419 – 4235cAMPBy similarity

    GO - Molecular functioni

    1. 3',5'-cyclic-AMP phosphodiesterase activity Source: MGI
    2. 3',5'-cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
    3. cAMP binding Source: Ensembl
    4. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. cAMP catabolic process Source: BHF-UCL
    2. cellular response to drug Source: MGI
    3. regulation of cAMP-mediated signaling Source: MGI
    4. regulation of protein kinase A signaling Source: MGI
    5. sensory perception of smell Source: MGI
    6. signal transduction Source: InterPro

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_203795. DARPP-32 events.
    UniPathwayiUPA00762; UER00747.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
    Gene namesi
    Name:Pde4a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:99558. Pde4a.

    Subcellular locationi

    Cytoplasmperinuclear region By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4APRO_0000198807Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei147 – 1471Phosphoserine; by MAPKAPK2By similarity
    Modified residuei160 – 1601PhosphoserineBy similarity
    Cross-linki344 – 344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Post-translational modificationi

    Proteolytically cleaved by caspase-3.By similarity
    Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO89084.
    PaxDbiO89084.
    PRIDEiO89084.

    PTM databases

    PhosphoSiteiO89084.

    Expressioni

    Gene expression databases

    ArrayExpressiO89084.
    BgeeiO89084.
    CleanExiMM_PDE4A.
    GenevestigatoriO89084.

    Interactioni

    Subunit structurei

    Interacts with LYN and ARRB2.By similarity

    Protein-protein interaction databases

    MINTiMINT-4996302.

    Structurei

    3D structure databases

    ProteinModelPortaliO89084.
    SMRiO89084. Positions 254-696.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni317 – 710394CatalyticBy similarityAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG122287.
    GeneTreeiENSGT00740000115148.
    HOGENOMiHOG000236297.
    HOVERGENiHBG108239.
    InParanoidiO89084.
    KOiK01120.
    OMAiPSPTMKD.
    OrthoDBiEOG7HQNBC.
    PhylomeDBiO89084.
    TreeFamiTF314638.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    InterProiIPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00471. HDc. 1 hit.
    [Graphical view]
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: O89084-1) [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

    MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD    50
    SAERSEPERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS 100
    RRLEAENGPT PSPGRSPLDS QASPGLMLHA GAATSQRRES FLYRSDSDYD 150
    MSPKTMSRNS SVASEAHGED LIVTPFAQVL ASLRNVRSNF SLLTNVPIPS 200
    NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS 250
    EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTP 300
    RQRPFQQPPP AAVQQAQPMS QITGLKKLVH TGSLNINVPR FGVKTDQEDL 350
    LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT 400
    MMTYMLTLED HYHADVAYHN SLHAADVLQS THVLLATPAL DAVFTDLEIL 450
    AALFAAAIHD VDHPGVSNQF LINTNSELAL MYNDESVLEN HHLAVGFKLL 500
    QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA DLKTMVETKK 550
    VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF 600
    QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD 650
    AQDILDTLED NRDWYHSAIR QSPSPTLEEE PGVLSDPALP DKFQFELTLE 700
    EEDEEDSLEV PGLPCTEETL LAPHDTRAQA MEQSKVKGQS PAVVEVAESL 750
    KQETASAHGA PEESAEAVGH SFSLETSILP DLRTLSPSEE AQGLLGLPSM 800
    AAEVEAPRDH LAAMRACSAC SGTSGDNSAV ISAPGRWGSG GDPA 844
    Length:844
    Mass (Da):93,558
    Last modified:March 1, 2002 - v2
    Checksum:i632396C9F70E0F61
    GO
    Isoform 2 (identifier: O89084-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-234: Missing.
         235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ

    Show »
    Length:610
    Mass (Da):68,190
    Checksum:i280D59FE2DFD67A5
    GO
    Isoform 3 (identifier: O89084-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-102: MEPPAAPSER...TGTGGGSSRR → MRSSAAPRAR...LRHPPGRCVS

    Show »
    Length:787
    Mass (Da):87,193
    Checksum:i703D813F13AB5E03
    GO

    Sequence cautioni

    The sequence AAH27224.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti516 – 5161R → K in AAF19201. (PubMed:11267656)Curated
    Sequence conflicti685 – 6851S → G in AAH27224. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 234234Missing in isoform 2. 2 PublicationsVSP_004563Add
    BLAST
    Alternative sequencei1 – 102102MEPPA…GSSRR → MRSSAAPRARPRPPALALPL GPESLTHFSFSEEDTLRHPP GRCVS in isoform 3. 1 PublicationVSP_004562Add
    BLAST
    Alternative sequencei235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 2. 2 PublicationsVSP_004564Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF142646
    , AF142643, AF142644, AF142645 Genomic DNA. Translation: AAF14519.1.
    AF142646, AF142644, AF142645 Genomic DNA. Translation: AAF14520.1.
    AF208021 mRNA. Translation: AAF19201.2.
    AJ297396 mRNA. Translation: CAB96769.1.
    BC027224 mRNA. Translation: AAH27224.2. Different initiation.
    U97586 mRNA. Translation: AAC25681.1.
    CCDSiCCDS22895.1. [O89084-1]
    CCDS22896.1. [O89084-2]
    RefSeqiNP_062772.3. NM_019798.5. [O89084-2]
    NP_899668.1. NM_183408.3. [O89084-1]
    XP_006510155.1. XM_006510092.1. [O89084-3]
    UniGeneiMm.191749.

    Genome annotation databases

    EnsembliENSMUST00000003395; ENSMUSP00000003395; ENSMUSG00000032177. [O89084-2]
    ENSMUST00000039413; ENSMUSP00000037025; ENSMUSG00000032177. [O89084-1]
    ENSMUST00000115458; ENSMUSP00000111118; ENSMUSG00000032177. [O89084-3]
    GeneIDi18577.
    KEGGimmu:18577.
    UCSCiuc009oki.2. mouse. [O89084-1]
    uc009okl.2. mouse. [O89084-3]
    uc009okm.2. mouse. [O89084-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF142646
    , AF142643 , AF142644 , AF142645 Genomic DNA. Translation: AAF14519.1 .
    AF142646 , AF142644 , AF142645 Genomic DNA. Translation: AAF14520.1 .
    AF208021 mRNA. Translation: AAF19201.2 .
    AJ297396 mRNA. Translation: CAB96769.1 .
    BC027224 mRNA. Translation: AAH27224.2 . Different initiation.
    U97586 mRNA. Translation: AAC25681.1 .
    CCDSi CCDS22895.1. [O89084-1 ]
    CCDS22896.1. [O89084-2 ]
    RefSeqi NP_062772.3. NM_019798.5. [O89084-2 ]
    NP_899668.1. NM_183408.3. [O89084-1 ]
    XP_006510155.1. XM_006510092.1. [O89084-3 ]
    UniGenei Mm.191749.

    3D structure databases

    ProteinModelPortali O89084.
    SMRi O89084. Positions 254-696.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4996302.

    Chemistry

    BindingDBi O89084.
    ChEMBLi CHEMBL2111373.

    PTM databases

    PhosphoSitei O89084.

    Proteomic databases

    MaxQBi O89084.
    PaxDbi O89084.
    PRIDEi O89084.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000003395 ; ENSMUSP00000003395 ; ENSMUSG00000032177 . [O89084-2 ]
    ENSMUST00000039413 ; ENSMUSP00000037025 ; ENSMUSG00000032177 . [O89084-1 ]
    ENSMUST00000115458 ; ENSMUSP00000111118 ; ENSMUSG00000032177 . [O89084-3 ]
    GeneIDi 18577.
    KEGGi mmu:18577.
    UCSCi uc009oki.2. mouse. [O89084-1 ]
    uc009okl.2. mouse. [O89084-3 ]
    uc009okm.2. mouse. [O89084-2 ]

    Organism-specific databases

    CTDi 5141.
    MGIi MGI:99558. Pde4a.

    Phylogenomic databases

    eggNOGi NOG122287.
    GeneTreei ENSGT00740000115148.
    HOGENOMi HOG000236297.
    HOVERGENi HBG108239.
    InParanoidi O89084.
    KOi K01120.
    OMAi PSPTMKD.
    OrthoDBi EOG7HQNBC.
    PhylomeDBi O89084.
    TreeFami TF314638.

    Enzyme and pathway databases

    UniPathwayi UPA00762 ; UER00747 .
    Reactomei REACT_203795. DARPP-32 events.

    Miscellaneous databases

    NextBioi 294438.
    PROi O89084.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O89084.
    Bgeei O89084.
    CleanExi MM_PDE4A.
    Genevestigatori O89084.

    Family and domain databases

    Gene3Di 1.10.1300.10. 1 hit.
    InterProi IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view ]
    Pfami PF00233. PDEase_I. 1 hit.
    [Graphical view ]
    PRINTSi PR00387. PDIESTERASE1.
    SMARTi SM00471. HDc. 1 hit.
    [Graphical view ]
    PROSITEi PS00126. PDEASE_I. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Physical mapping and promoter structure of the murine cAMP-specific phosphodiesterase pde4a gene."
      Olsen A.E., Bolger G.B.
      Mamm. Genome 11:41-45(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
      Tissue: Embryonic stem cell.
    2. "Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse."
      Cherry J.A., Thompson B.E., Pho V.
      Biochim. Biophys. Acta 1518:27-35(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ENZYME REGULATION.
      Strain: Swiss Webster.
      Tissue: Brain.
    3. "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 3).
      Strain: FVB/N.
      Tissue: Salivary gland.
    4. "Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2."
      Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.
      Biochem. J. 333:693-703(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 248-355 (ISOFORM 2).
      Tissue: Brain.

    Entry informationi

    Entry nameiPDE4A_MOUSE
    AccessioniPrimary (citable) accession number: O89084
    Secondary accession number(s): Q8R078
    , Q9JHQ4, Q9QX48, Q9QX49, Q9QXI8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 19, 2002
    Last sequence update: March 1, 2002
    Last modified: October 1, 2014
    This is version 114 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

    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