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O77746

- PDE5A_CANFA

UniProt

O77746 - PDE5A_CANFA

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Protein
cGMP-specific 3',5'-cyclic phosphodiesterase
Gene
PDE5A, PDE5
Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.

Enzyme regulationi

Inhibited by zaprinast.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei603 – 6031Proton donor By similarity
Metal bindingi607 – 6071Divalent metal cation 1 By similarity
Metal bindingi643 – 6431Divalent metal cation 1 By similarity
Metal bindingi644 – 6441Divalent metal cation 1 By similarity
Metal bindingi644 – 6441Divalent metal cation 2 By similarity
Metal bindingi754 – 7541Divalent metal cation 1 By similarity
Binding sitei807 – 8071cGMP By 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 T cell proliferation Source: Ensembl
  3. negative regulation of cardiac muscle contraction Source: Ensembl
  4. positive regulation of MAP kinase activity Source: Ensembl
  5. positive regulation of cardiac muscle hypertrophy Source: Ensembl
  6. positive regulation of oocyte development Source: Ensembl
  7. relaxation of cardiac muscle Source: Ensembl
  8. signal transduction Source: InterPro
Complete GO annotation...

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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterase
PRO_0000198822Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei92 – 921Phosphoserine Reviewed prediction

Post-translational modificationi

Phosphorylation is regulated by binding of cGMP to the two allosteric sites By similarity. 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.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni578 – 843266Catalytic By similarity
Add
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.

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.
VSP_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: June 11, 2014
This is version 97 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

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