Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O77746

- PDE5A_CANFA

UniProt

O77746 - PDE5A_CANFA

Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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.

    Catalytic activityi

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

    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: UniProtKB-EC
    2. cGMP binding Source: UniProtKB-KW
    3. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. cGMP catabolic process Source: UniProtKB-UniPathway
    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

    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
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Chromosome 32

    Subcellular locationi

    Cytoplasm. Cytoplasmcytosol
    Note: PDE5A1 and PDE5A2 are located mostly to soluble cellular fractions and some to particulate cellular fractions.

    GO - Cellular componenti

    1. cytosol Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterasePRO_0000198822Add
    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

    Keywords - PTMi

    Phosphoprotein

    Expressioni

    Tissue specificityi

    Isoform PDE5A1 and isoform PDE5A2 are highly expressed in the cerebellum, hippocampus, retina, lung, heart, spleen, and thoracic artery. Isoform PDE5A1, but not isoform PDE5A2, is also abundantly expressed in the pylorus.

    Interactioni

    Protein-protein interaction databases

    STRINGi9615.ENSCAFP00000034752.

    Structurei

    3D structure databases

    ProteinModelPortaliO77746.
    SMRiO77746. 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.
    InParanoidiO77746.
    KOiK13762.
    OMAiHIRSLLC.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform PDE5A1 (identifier: O77746-1) [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

    MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE    50
    RVHTIPVCKE GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL 100
    RPIVVKDSEG TVSFLADSEK KEQMPLTPPR FDNDEGDQCS RLLELVKDIS 150
    SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSNDKFL ISRLFDVAEG 200
    STLEEASNNC IRLEWNKGIV GHVAALGEPL NIKDAYEDPR FNAEVDQITG 250
    YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC 300
    GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS 350
    FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKLPDTLTR ERDANRINYM 400
    YAQYVKNTME PLNIPDVSKD KRFPWTNENT GNVNQQCIRS LLCTPIKNGK 450
    KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ FLEAFVIFCG LGIQNTQMYE 500
    AVERAMAKQM VTLEVLSYHA SAAEEETKEL QSLAAAVVPS AQTLKITDFS 550
    FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV 600
    AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV 650
    NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK 700
    TTLKIIKQAI LATDLALYIK RRGEFFELIR KNQFNLEDPH QKELFLAMLM 750
    TACDLSAITK PWPIQQRIAE LVATEFFDQG DRERKELNIE PADLMNREKK 800
    NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR QKWQALAEQQ 850
    EKTLINGESS QAKRN 865
    Length:865
    Mass (Da):98,294
    Last modified:November 1, 1998 - v1
    Checksum:iF20BB37B71E93BB6
    GO
    Isoform PDE5A2 (identifier: O77746-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-40: MERGSPGAGAARLPRDQDSVEAWLDDHRDFTFSYFVKKAT → MLPFGHQR

    Show »
    Length:833
    Mass (Da):94,750
    Checksum:iAC03A9F087128BC3
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4040MERGS…VKKAT → MLPFGHQR in isoform PDE5A2. 1 PublicationVSP_004590Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB008467 mRNA. Translation: BAA33503.1.
    AB008468 mRNA. Translation: BAA33504.1.
    RefSeqiNP_001003188.1. NM_001003188.1. [O77746-2]
    XP_005639100.1. XM_005639043.1. [O77746-1]
    UniGeneiCfa.1752.

    Genome annotation databases

    EnsembliENSCAFT00000019808; ENSCAFP00000018375; ENSCAFG00000012472. [O77746-2]
    ENSCAFT00000038959; ENSCAFP00000034752; ENSCAFG00000012472. [O77746-1]
    GeneIDi403825.
    KEGGicfa:403825.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB008467 mRNA. Translation: BAA33503.1 .
    AB008468 mRNA. Translation: BAA33504.1 .
    RefSeqi NP_001003188.1. NM_001003188.1. [O77746-2 ]
    XP_005639100.1. XM_005639043.1. [O77746-1 ]
    UniGenei Cfa.1752.

    3D structure databases

    ProteinModelPortali O77746.
    SMRi O77746. Positions 154-301, 525-850.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9615.ENSCAFP00000034752.

    Chemistry

    ChEMBLi CHEMBL2304402.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSCAFT00000019808 ; ENSCAFP00000018375 ; ENSCAFG00000012472 . [O77746-2 ]
    ENSCAFT00000038959 ; ENSCAFP00000034752 ; ENSCAFG00000012472 . [O77746-1 ]
    GeneIDi 403825.
    KEGGi cfa:403825.

    Organism-specific databases

    CTDi 8654.

    Phylogenomic databases

    eggNOGi NOG270709.
    GeneTreei ENSGT00750000117528.
    HOGENOMi HOG000007068.
    HOVERGENi HBG101207.
    InParanoidi O77746.
    KOi K13762.
    OMAi HIRSLLC.
    OrthoDBi EOG7RRF69.
    TreeFami TF316499.

    Enzyme and pathway databases

    UniPathwayi UPA00763 ; UER00748 .

    Miscellaneous databases

    NextBioi 20817321.

    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. "Novel alternative splice variants of cGMP-binding cGMP-specific phosphodiesterase."
      Kotera J., Fujishige K., Akatsuka H., Imai Y., Yanaka N., Omori K.
      J. Biol. Chem. 273:26982-26990(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE5A1 AND PDE5A2).
      Tissue: Lung.

    Entry informationi

    Entry nameiPDE5A_CANFA
    AccessioniPrimary (citable) accession number: O77746
    Secondary accession number(s): O77747
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 98 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    cGMP-binding to the allosteric sites is stimulated by 3-isobutyl-1-methylxanthine (IBMX).

    Keywords - Technical termi

    Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3