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P54748

- PDE4A_RAT

UniProt

P54748 - PDE4A_RAT

Protein

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

Gene

Pde4a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      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.

    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: RGD
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: RGD

    GO - Biological processi

    1. cAMP catabolic process Source: UniProtKB
    2. response to drug Source: RGD
    3. signal transduction Source: InterPro

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    UniPathwayiUPA00762; UER00747.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
    Alternative name(s):
    DPDE2
    Gene namesi
    Name:Pde4a
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3279. Pde4a.

    Subcellular locationi

    Cytoplasmperinuclear region By similarity

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. cytosol Source: RGD
    3. nucleus Source: RGD
    4. perinuclear region of cytoplasm Source: RGD

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi147 – 1471S → A: Abolishes phosphorylation by MAPKAPK2. 1 Publication
    Mutagenesisi161 – 1611S → A: Does not affect phosphorylation by MAPKAPK2. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4APRO_0000198808Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei147 – 1471Phosphoserine; by MAPKAPK21 Publication
    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.1 Publication

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP54748.
    PRIDEiP54748.

    PTM databases

    PhosphoSiteiP54748.

    Miscellaneous databases

    PMAP-CutDBP54748.

    Expressioni

    Tissue specificityi

    Isoform 2 is testis specific.

    Gene expression databases

    GenevestigatoriP54748.

    Interactioni

    Subunit structurei

    Interacts with LYN and ARRB2.By similarity

    Structurei

    Secondary structure

    1
    844
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 97
    Helixi16 – 194
    Helixi20 – 234

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LOINMR-A1-25[»]
    ProteinModelPortaliP54748.
    SMRiP54748. Positions 337-698.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP54748.

    Family & Domainsi

    Region

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

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG122287.
    HOGENOMiHOG000236297.
    HOVERGENiHBG108239.
    InParanoidiP54748.
    KOiK01120.
    PhylomeDBiP54748.

    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 (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P54748-1) [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 IRIQQRGYPD    50
    SAERSETERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS 100
    RRLEAENGPT PSPGRSPLDS QASPGLVLHA GATTSQRRES FLYRSDSDYD 150
    MSPKAVSRSS SVASEAHAED LIVTPFAQVL ASLRSVRSNF SLLTNVPIPS 200
    NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS 250
    EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP 300
    RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL 350
    LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT 400
    MMMYMLTLED 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 QSPSPPLEEE PGGLGHPSLP DKFQFELTLE 700
    EEEEEDSLEV PGLPTTEETF LAAEDARAQA VDWSKVKGPS TTVVEVAERL 750
    KQETASAYGA PQESMEAVGC SFSPGTPILP DVRTLSSSEE APGLLGLPST 800
    AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG GDPA 844
    Length:844
    Mass (Da):93,439
    Last modified:October 1, 1996 - v1
    Checksum:i1A5F5101E4DBF1B6
    GO
    Isoform 2 (identifier: P54748-2) [UniParc]FASTAAdd to Basket

    Also known as: PDE4A8

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

    Show »
    Length:763
    Mass (Da):84,647
    Checksum:i9E1E33481260566A
    GO
    Isoform 3 (identifier: P54748-3) [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):68,161
    Checksum:iFE439ACE95E1D1AC
    GO
    Isoform 4 (identifier: P54748-4) [UniParc]FASTAAdd to Basket

    Also known as: Medium

    The sequence of this isoform differs from the canonical sequence as follows:
         1-259: Missing.

    Show »
    Length:585
    Mass (Da):65,059
    Checksum:i3A188A286A28E174
    GO
    Isoform 5 (identifier: P54748-5) [UniParc]FASTAAdd to Basket

    Also known as: Short

    The sequence of this isoform differs from the canonical sequence as follows:
         1-318: Missing.
         354-386: Missing.

    Show »
    Length:493
    Mass (Da):54,526
    Checksum:i53735B34F1122F97
    GO
    Isoform 6 (identifier: P54748-6) [UniParc]FASTAAdd to Basket

    Also known as: PDE4A10

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

    Note: Incomplete sequence.

    Show »
    Length:771
    Mass (Da):85,344
    Checksum:iC1DB345199B5D59C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti130 – 1301A → R in AAF14352. (PubMed:11306681)Curated
    Sequence conflicti465 – 4662GV → AL in AAA41848. (PubMed:2546153)Curated
    Sequence conflicti465 – 4662GV → AL in AAA41823. (PubMed:2546153)Curated
    Sequence conflicti603 – 6042GD → AH in AAA41848. (PubMed:2546153)Curated
    Sequence conflicti603 – 6042GD → AH in AAA41823. (PubMed:2546153)Curated
    Sequence conflicti833 – 8331A → T in AAC37699. (PubMed:2542942)Curated
    Sequence conflicti833 – 8331A → T in AAA41101. (PubMed:2542942)Curated
    Sequence conflicti833 – 8331A → T in AAA41102. (PubMed:2542942)Curated
    Sequence conflicti833 – 8331A → T in AAF14352. (PubMed:11306681)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 318318Missing in isoform 5. 2 PublicationsVSP_004569Add
    BLAST
    Alternative sequencei1 – 259259Missing in isoform 4. 2 PublicationsVSP_004568Add
    BLAST
    Alternative sequencei1 – 234234Missing in isoform 3. 2 PublicationsVSP_004566Add
    BLAST
    Alternative sequencei1 – 102102MEPPA…GSSRR → MPSRKRLTLPRIFIVRKNGN S in isoform 2. 1 PublicationVSP_004565Add
    BLAST
    Alternative sequencei1 – 102102MEPPA…GSSRR → ALPLGPESLTHFSFSEEDTL RHPPGRCVS in isoform 6. CuratedVSP_038187Add
    BLAST
    Alternative sequencei235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 3. 2 PublicationsVSP_004567Add
    BLAST
    Alternative sequencei354 – 38633Missing in isoform 5. 2 PublicationsVSP_004570Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27057 mRNA. Translation: AAC27098.1.
    L36467 mRNA. Translation: AAB00357.1.
    L27062 mRNA. Translation: AAA56859.1.
    M25348 mRNA. Translation: AAA41848.1.
    M28411 mRNA. Translation: AAA41823.1.
    M26715 mRNA. Translation: AAC37699.1.
    M26716 mRNA. Translation: AAA41101.1.
    M26717 mRNA. Translation: AAA41102.1.
    AF110461 mRNA. Translation: AAF14352.2.
    PIRiI53865.
    I67946.
    RefSeqiNP_037233.3. NM_013101.3. [P54748-1]
    UniGeneiRn.91357.

    Genome annotation databases

    GeneIDi25638.
    KEGGirno:25638.
    UCSCiRGD:3279. rat. [P54748-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27057 mRNA. Translation: AAC27098.1 .
    L36467 mRNA. Translation: AAB00357.1 .
    L27062 mRNA. Translation: AAA56859.1 .
    M25348 mRNA. Translation: AAA41848.1 .
    M28411 mRNA. Translation: AAA41823.1 .
    M26715 mRNA. Translation: AAC37699.1 .
    M26716 mRNA. Translation: AAA41101.1 .
    M26717 mRNA. Translation: AAA41102.1 .
    AF110461 mRNA. Translation: AAF14352.2 .
    PIRi I53865.
    I67946.
    RefSeqi NP_037233.3. NM_013101.3. [P54748-1 ]
    UniGenei Rn.91357.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1LOI NMR - A 1-25 [» ]
    ProteinModelPortali P54748.
    SMRi P54748. Positions 337-698.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P54748.
    ChEMBLi CHEMBL2094267.

    PTM databases

    PhosphoSitei P54748.

    Proteomic databases

    PaxDbi P54748.
    PRIDEi P54748.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25638.
    KEGGi rno:25638.
    UCSCi RGD:3279. rat. [P54748-1 ]

    Organism-specific databases

    CTDi 5141.
    RGDi 3279. Pde4a.

    Phylogenomic databases

    eggNOGi NOG122287.
    HOGENOMi HOG000236297.
    HOVERGENi HBG108239.
    InParanoidi P54748.
    KOi K01120.
    PhylomeDBi P54748.

    Enzyme and pathway databases

    UniPathwayi UPA00762 ; UER00747 .

    Miscellaneous databases

    EvolutionaryTracei P54748.
    NextBioi 607467.
    PMAP-CutDB P54748.

    Gene expression databases

    Genevestigatori P54748.

    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. "Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene."
      Davis R.L., Takayasu H., Eberwine M., Myres J.
      Proc. Natl. Acad. Sci. U.S.A. 86:3604-3608(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5).
    2. "Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases."
      Bolger G.B., Rodgers L., Riggs M.
      Gene 149:237-244(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
      Tissue: Brain.
    3. "Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts. Characterization of a novel tissue-specific isoform, RNPDE4A8."
      Bolger G.B., McPhee I., Houslay M.D.
      J. Biol. Chem. 271:1065-1071(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Strain: Sprague-Dawley.
      Tissue: Testis.
    4. "Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes."
      Swinnen J.V., Joseph D.R., Conti M.
      Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 319-677 (ISOFORMS 3/4).
      Tissue: Testis.
    5. "Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic AMP-specific phosphodiesterase PDE4A10."
      Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E., Sullivan M., Houslay M.D.
      Mol. Pharmacol. 59:996-1011(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
    6. "Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation."
      MacKenzie K.F., Wallace D.A., Hill E.V., Anthony D.F., Henderson D.J., Houslay D.M., Arthur J.S., Baillie G.S., Houslay M.D.
      Biochem. J. 435:755-769(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-147, MUTAGENESIS OF SER-147 AND SER-161.
    7. "Determination of the structure of the N-terminal splice region of the cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and identification of the membrane association domain using chimeric constructs."
      Smith K.J., Scotland G., Beattie J., Trayer I.P., Houslay M.D.
      J. Biol. Chem. 271:16703-16711(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-26 OF ISOFORM 3.

    Entry informationi

    Entry nameiPDE4A_RAT
    AccessioniPrimary (citable) accession number: P54748
    Secondary accession number(s): P14645, Q9EQR7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 114 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3