Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q28156

- PDE5A_BOVIN

UniProt

Q28156 - PDE5A_BOVIN

(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)

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

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
Complete GO annotation...

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.
GeneTreeiENSGT00760000119066.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MERAGPGSAR PQQQWDQDSV EAWLDDHWDF TFSYFVRKGT REMVNAWFAE
60 70 80 90 100
RVHTIPVCKE GIKGHTESCS CPLQPSPRAE SSVPGTPTRK ISASEFDRPL
110 120 130 140 150
RPIVIKDSEG TVSFLSDSDK KEQMPLTSPR FDNDEGDQCS RLLELVKDIS
160 170 180 190 200
SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSNDKFL ISRLFDVAEG
210 220 230 240 250
STLEEASNNC IRLEWNKGIV GHVAAFGEPL NIKDAYEDPR FNAEVDQITG
260 270 280 290 300
YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC
310 320 330 340 350
GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS
360 370 380 390 400
FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR ERDANRINYM
410 420 430 440 450
YAQYVKNTME PLNIPDVSKD KRFPWTNENM GNINQQCIRS LLCTPIKNGK
460 470 480 490 500
KNKVIGVCQL VNKMEETTGK VKAFNRNDEQ FLEAFVIFCG LGIQNTQMYE
510 520 530 540 550
AVERAMAKQM VTLEVLSYHA SAAEEETREL QSLAAAVVPS AQTLKITDFS
560 570 580 590 600
FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCKWIL SVKKNYRKNV
610 620 630 640 650
AYHNWRHAFN TAQCMFAALK AGKIQKRLTD LEILALLIAA LSHDLDHRGV
660 670 680 690 700
NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK
710 720 730 740 750
TTLKIIKQAI LATDLALYIK RRGEFFELIM KNQFNLEDPH QKELFLAMLM
760 770 780 790 800
TACDLSAITK PWPIQQRIAE LVATEFFDQG DRERKELNIE PADLMNREKK
810 820 830 840 850
NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR QKWQALAEQQ
860
EKTLINGESS QTKRN
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 ENSGT00760000119066.
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 29, 2014
This is version 111 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