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Q28156 (PDE5A_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length865 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. Ref.3

Catalytic activity

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

Cofactor

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.

Enzyme regulation

Most potently inhibited by zaprinast and dipyridamole.

Pathway

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

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. Phosphorylation by PRKG1 leads to its activation By similarity.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Contains 2 GAF domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterase
PRO_0000198821

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

Experimental info

Mutagenesis2761N → A: Decreased cGMP-binding; no change in catalytic activity. Ref.4
Mutagenesis2771K → A: Decreased cGMP-binding; no change in catalytic activity. Ref.4
Mutagenesis2771K → R: Slight increase in cGMP-binding. Ref.4
Mutagenesis2891D → A: Decreased cGMP-binding; no change in catalytic activity. Ref.3 Ref.4 Ref.5
Mutagenesis2891D → N: Increased cGMP-binding; no change in catalytic activity. Ref.3 Ref.4 Ref.5
Mutagenesis2901E → A: No change in cGMP-binding. Ref.4
Mutagenesis4781D → A: Increased cGMP-binding; no change in catalytic activity. Phosphorylated at lower concentrations of cGMP. Ref.3 Ref.5

Secondary structure

................................. 865
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q28156 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 2FF7144B2990B4F7

FASTA86598,627
        10         20         30         40         50         60 
MERAGPGSAR PQQQWDQDSV EAWLDDHWDF TFSYFVRKGT REMVNAWFAE RVHTIPVCKE 

        70         80         90        100        110        120 
GIKGHTESCS CPLQPSPRAE SSVPGTPTRK ISASEFDRPL RPIVIKDSEG TVSFLSDSDK 

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

       190        200        210        220        230        240 
CEDSSNDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAAFGEPL 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 LEKSSDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD 

       430        440        450        460        470        480 
KRFPWTNENM GNINQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEETTGK VKAFNRNDEQ 

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

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

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

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

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

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

       850        860 
QKWQALAEQQ EKTLINGESS QTKRN 

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References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L16545 mRNA. Translation: AAB00990.1.
RefSeqNP_776842.1. NM_174417.2.
UniGeneBt.540.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FL4model-A118-309[»]
ProteinModelPortalQ28156.
SMRQ28156. Positions 154-301, 525-850.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000014479.

Chemistry

BindingDBQ28156.
ChEMBLCHEMBL3478.

Proteomic databases

PRIDEQ28156.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000014479; ENSBTAP00000014479; ENSBTAG00000024888.
GeneID281972.
KEGGbta:281972.

Organism-specific databases

CTD8654.

Phylogenomic databases

eggNOGNOG270709.
GeneTreeENSGT00750000117528.
HOGENOMHOG000007068.
HOVERGENHBG101207.
InParanoidQ28156.
KOK13762.
OMAREHDANK.
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

NextBio20805843.

Entry information

Entry namePDE5A_BOVIN
AccessionPrimary (citable) accession number: Q28156
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: June 11, 2014
This is version 108 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways