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O77746 (PDE5A_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PDE5A
Synonyms:PDE5
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length865 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

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

Cofactor

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 regulation

Inhibited by zaprinast.

Pathway

Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.

Subcellular location

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

Tissue specificity

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.

Domain

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.

Post-translational modification

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

Miscellaneous

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

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Contains 2 GAF domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform PDE5A1 (identifier: O77746-1)

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.
Isoform PDE5A2 (identifier: O77746-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterase
PRO_0000198822

Regions

Domain154 – 304151GAF 1
Domain336 – 493158GAF 2
Region578 – 843266Catalytic By similarity

Sites

Active site6031Proton donor By similarity
Metal binding6071Divalent metal cation 1 By similarity
Metal binding6431Divalent metal cation 1 By similarity
Metal binding6441Divalent metal cation 1 By similarity
Metal binding6441Divalent metal cation 2 By similarity
Metal binding7541Divalent metal cation 1 By similarity
Binding site8071cGMP By similarity

Amino acid modifications

Modified residue921Phosphoserine Potential

Natural variations

Alternative sequence1 – 4040MERGS…VKKAT → MLPFGHQR in isoform PDE5A2.
VSP_004590

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE5A1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: F20BB37B71E93BB6

FASTA86598,294
        10         20         30         40         50         60 
MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE RVHTIPVCKE 

        70         80         90        100        110        120 
GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL RPIVVKDSEG TVSFLADSEK 

       130        140        150        160        170        180 
KEQMPLTPPR FDNDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV 

       190        200        210        220        230        240 
CEDSSNDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAALGEPL NIKDAYEDPR 

       250        260        270        280        290        300 
FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC 

       310        320        330        340        350        360 
GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS FMQVQKCTIF 

       370        380        390        400        410        420 
IVDEDCSDSF SSVFHMECEE LEKLPDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD 

       430        440        450        460        470        480 
KRFPWTNENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ 

       490        500        510        520        530        540 
FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETKEL QSLAAAVVPS 

       550        560        570        580        590        600 
AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV 

       610        620        630        640        650        660 
AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV NNSYIQRSEH 

       670        680        690        700        710        720 
PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI LATDLALYIK 

       730        740        750        760        770        780 
RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE LVATEFFDQG 

       790        800        810        820        830        840 
DRERKELNIE PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR 

       850        860 
QKWQALAEQQ EKTLINGESS QAKRN 

« Hide

Isoform PDE5A2 [UniParc].

Checksum: AC03A9F087128BC3
Show »

FASTA83394,750

References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB008467 mRNA. Translation: BAA33503.1.
AB008468 mRNA. Translation: BAA33504.1.
RefSeqNP_001003188.1. NM_001003188.1. [O77746-2]
XP_005639100.1. XM_005639043.1. [O77746-1]
UniGeneCfa.1752.

3D structure databases

ProteinModelPortalO77746.
SMRO77746. Positions 154-301, 525-850.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9615.ENSCAFP00000034752.

Chemistry

ChEMBLCHEMBL2304402.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSCAFT00000019808; ENSCAFP00000018375; ENSCAFG00000012472. [O77746-2]
ENSCAFT00000038959; ENSCAFP00000034752; ENSCAFG00000012472. [O77746-1]
GeneID403825.
KEGGcfa:403825.

Organism-specific databases

CTD8654.

Phylogenomic databases

eggNOGNOG270709.
GeneTreeENSGT00750000117528.
HOGENOMHOG000007068.
HOVERGENHBG101207.
InParanoidO77746.
KOK13762.
OMAHIRSLLC.
OrthoDBEOG7RRF69.
TreeFamTF316499.

Enzyme and pathway databases

UniPathwayUPA00763; UER00748.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProIPR003018. GAF.
IPR029016. GAF_dom_like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMSSF55781. SSF55781. 2 hits.
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20817321.

Entry information

Entry namePDE5A_CANFA
AccessionPrimary (citable) accession number: O77746
Secondary accession number(s): O77747
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways