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Q28156

- PDE5A_BOVIN

UniProt

Q28156 - PDE5A_BOVIN

Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.1 Publication

    Catalytic activityi

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

    Cofactori

    Binds 2 divalent metal cations per subunit By similarity. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.By similarity

    Enzyme regulationi

    Most potently inhibited by zaprinast and dipyridamole.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei603 – 6031Proton donorBy similarity
    Metal bindingi607 – 6071Divalent metal cation 1By similarity
    Metal bindingi643 – 6431Divalent metal cation 1By similarity
    Metal bindingi644 – 6441Divalent metal cation 1By similarity
    Metal bindingi644 – 6441Divalent metal cation 2By similarity
    Metal bindingi754 – 7541Divalent metal cation 1By similarity
    Binding sitei807 – 8071cGMPBy similarity

    GO - Molecular functioni

    1. 3',5'-cyclic-GMP phosphodiesterase activity Source: AgBase
    2. cGMP binding Source: AgBase
    3. cyclic-nucleotide phosphodiesterase activity Source: AgBase
    4. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. cGMP catabolic process Source: AgBase
    2. negative regulation of cardiac muscle contraction Source: Ensembl
    3. negative regulation of T cell proliferation Source: Ensembl
    4. positive regulation of cardiac muscle hypertrophy Source: Ensembl
    5. positive regulation of MAP kinase activity Source: Ensembl
    6. positive regulation of oocyte development Source: Ensembl
    7. relaxation of cardiac muscle Source: Ensembl
    8. signal transduction Source: InterPro

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

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

    Enzyme and pathway databases

    ReactomeiREACT_205403. cGMP effects.
    UniPathwayiUPA00763; UER00748.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cGMP-specific 3',5'-cyclic phosphodiesterase (EC:3.1.4.35)
    Alternative name(s):
    cGMP-binding cGMP-specific phosphodiesterase
    Short name:
    CGB-PDE
    Gene namesi
    Name:PDE5A
    Synonyms:PDE5
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 6

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi276 – 2761N → A: Decreased cGMP-binding; no change in catalytic activity. 1 Publication
    Mutagenesisi277 – 2771K → A: Decreased cGMP-binding; no change in catalytic activity. 1 Publication
    Mutagenesisi277 – 2771K → R: Slight increase in cGMP-binding. 1 Publication
    Mutagenesisi289 – 2891D → A: Decreased cGMP-binding; no change in catalytic activity. 3 Publications
    Mutagenesisi289 – 2891D → N: Increased cGMP-binding; no change in catalytic activity. 3 Publications
    Mutagenesisi290 – 2901E → A: No change in cGMP-binding. 1 Publication
    Mutagenesisi478 – 4781D → A: Increased cGMP-binding; no change in catalytic activity. Phosphorylated at lower concentrations of cGMP. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterasePRO_0000198821Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei92 – 921PhosphoserineSequence Analysis

    Post-translational modificationi

    Phosphorylation is regulated by binding of cGMP to the two allosteric sites. Phosphorylation by PRKG1 leads to its activation By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ28156.

    Interactioni

    Protein-protein interaction databases

    STRINGi9913.ENSBTAP00000014479.

    Structurei

    Secondary structure

    1
    865
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni125 – 1273
    Helixi135 – 14915
    Turni155 – 1573
    Helixi158 – 17013
    Beta strandi173 – 1808
    Turni186 – 1883
    Beta strandi189 – 1924
    Beta strandi194 – 1974
    Beta strandi211 – 2144
    Helixi218 – 2269
    Beta strandi230 – 2334
    Beta strandi235 – 2373
    Beta strandi249 – 2513
    Beta strandi254 – 26613
    Beta strandi268 – 2758
    Helixi278 – 2803
    Helixi287 – 30216

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FL4model-A118-309[»]
    ProteinModelPortaliQ28156.
    SMRiQ28156. Positions 154-301, 525-850.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini154 – 304151GAF 1Add
    BLAST
    Domaini336 – 493158GAF 2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni578 – 843266CatalyticBy similarityAdd
    BLAST

    Domaini

    Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.

    Sequence similaritiesi

    Contains 2 GAF domains.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG270709.
    GeneTreeiENSGT00750000117528.
    HOGENOMiHOG000007068.
    HOVERGENiHBG101207.
    InParanoidiQ28156.
    KOiK13762.
    OMAiREHDANK.
    OrthoDBiEOG7RRF69.
    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]

    Sequencei

    Sequence statusi: Complete.

    Q28156-1 [UniParc]FASTAAdd to Basket

    « Hide

    MERAGPGSAR PQQQWDQDSV EAWLDDHWDF TFSYFVRKGT REMVNAWFAE    50
    RVHTIPVCKE GIKGHTESCS CPLQPSPRAE SSVPGTPTRK ISASEFDRPL 100
    RPIVIKDSEG TVSFLSDSDK KEQMPLTSPR FDNDEGDQCS RLLELVKDIS 150
    SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSNDKFL ISRLFDVAEG 200
    STLEEASNNC IRLEWNKGIV GHVAAFGEPL NIKDAYEDPR FNAEVDQITG 250
    YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC 300
    GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS 350
    FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR ERDANRINYM 400
    YAQYVKNTME PLNIPDVSKD KRFPWTNENM GNINQQCIRS LLCTPIKNGK 450
    KNKVIGVCQL VNKMEETTGK VKAFNRNDEQ FLEAFVIFCG LGIQNTQMYE 500
    AVERAMAKQM VTLEVLSYHA SAAEEETREL QSLAAAVVPS AQTLKITDFS 550
    FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCKWIL SVKKNYRKNV 600
    AYHNWRHAFN TAQCMFAALK AGKIQKRLTD LEILALLIAA LSHDLDHRGV 650
    NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK 700
    TTLKIIKQAI LATDLALYIK RRGEFFELIM KNQFNLEDPH QKELFLAMLM 750
    TACDLSAITK PWPIQQRIAE LVATEFFDQG DRERKELNIE PADLMNREKK 800
    NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR QKWQALAEQQ 850
    EKTLINGESS QTKRN 865
    Length:865
    Mass (Da):98,627
    Last modified:November 1, 1996 - v1
    Checksum:i2FF7144B2990B4F7
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L16545 mRNA. Translation: AAB00990.1.
    RefSeqiNP_776842.1. NM_174417.2.
    UniGeneiBt.540.

    Genome annotation databases

    EnsembliENSBTAT00000014479; ENSBTAP00000014479; ENSBTAG00000024888.
    GeneIDi281972.
    KEGGibta:281972.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L16545 mRNA. Translation: AAB00990.1 .
    RefSeqi NP_776842.1. NM_174417.2.
    UniGenei Bt.540.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FL4 model - A 118-309 [» ]
    ProteinModelPortali Q28156.
    SMRi Q28156. Positions 154-301, 525-850.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9913.ENSBTAP00000014479.

    Chemistry

    BindingDBi Q28156.
    ChEMBLi CHEMBL3478.

    Proteomic databases

    PRIDEi Q28156.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000014479 ; ENSBTAP00000014479 ; ENSBTAG00000024888 .
    GeneIDi 281972.
    KEGGi bta:281972.

    Organism-specific databases

    CTDi 8654.

    Phylogenomic databases

    eggNOGi NOG270709.
    GeneTreei ENSGT00750000117528.
    HOGENOMi HOG000007068.
    HOVERGENi HBG101207.
    InParanoidi Q28156.
    KOi K13762.
    OMAi REHDANK.
    OrthoDBi EOG7RRF69.
    TreeFami TF316499.

    Enzyme and pathway databases

    UniPathwayi UPA00763 ; UER00748 .
    Reactomei REACT_205403. cGMP effects.

    Miscellaneous databases

    NextBioi 20805843.

    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. "The structure of a bovine lung cGMP-binding, cGMP-specific phosphodiesterase deduced from a cDNA clone."
      McAllister-Lucas L.M., Sonnenburg W.K., Kadlecek A., Seger D., Trong H.L., Colbran J.L., Thomas M.K., Walsh K.A., Francis S.H., Corbin J.D., Beavo J.A.
      J. Biol. Chem. 268:22863-22873(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 4-16; 39-55; 90-101; 127-138; 390-409 AND 531-539.
      Tissue: Lung.
    2. "Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase."
      Francis S.H., Colbran J.L., McAllister-Lucas L.M., Corbin J.D.
      J. Biol. Chem. 269:22477-22480(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: METAL-BINDING.
    3. "An essential aspartic acid at each of two allosteric cGMP-binding sites of a cGMP-specific phosphodiesterase."
      McAllister-Lucas L.M., Haik T.L., Colbran J.L., Sonnenburg W.K., Seger D., Turko I.V., Beavo J.A., Francis S.H., Corbin J.D.
      J. Biol. Chem. 270:30671-30679(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-289 AND ASP-478.
    4. "Identification of key amino acids in a conserved cGMP-binding site of cGMP-binding phosphodiesterases. A putative NKXnD motif for cGMP binding."
      Turko I.V., Haik T.L., McAllister-Lucas L.M., Burns F., Francis S.H., Corbin J.D.
      J. Biol. Chem. 271:22240-22244(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASN-276; LYS-277; ASP-289 AND GLU-290.
    5. "Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation."
      Turko I.V., Francis S.H., Corbin J.D.
      Biochem. J. 329:505-510(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, MUTAGENESIS OF ASP-289 AND ASP-478.

    Entry informationi

    Entry nameiPDE5A_BOVIN
    AccessioniPrimary (citable) accession number: Q28156
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 110 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, Allosteric enzyme, Complete proteome, Direct protein sequencing, 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