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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

Pde5a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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. Specifically regulates nitric-oxide-generated cGMP.By similarity

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 Zn2+ ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.By similarity
  • Mg2+By similarityNote: Binds 1 Mg2+ ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.By similarity

Pathwayi: 3',5'-cyclic GMP degradation

This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cGMP-specific 3',5'-cyclic phosphodiesterase (Pde5a), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (Pde9a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a)
This subpathway is part of the pathway 3',5'-cyclic GMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei603Proton donorBy similarity1
Metal bindingi607Zinc; via tele nitrogenBy similarity1
Metal bindingi643Zinc; via tele nitrogenBy similarity1
Metal bindingi644MagnesiumBy similarity1
Metal bindingi644ZincBy similarity1
Metal bindingi754ZincBy similarity1
Binding sitei807cGMPBy similarity1

GO - Molecular functioni

  • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC
  • 3',5'-cyclic-nucleotide phosphodiesterase activity Source: MGI
  • cGMP binding Source: MGI
  • cyclic-nucleotide phosphodiesterase activity Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cGMP catabolic process Source: MGI
  • cGMP metabolic process Source: MGI
  • negative regulation of cardiac muscle contraction Source: BHF-UCL
  • negative regulation of T cell proliferation Source: MGI
  • positive regulation of cardiac muscle hypertrophy Source: BHF-UCL
  • positive regulation of G-protein coupled receptor protein signaling pathway Source: BHF-UCL
  • positive regulation of MAP kinase activity Source: BHF-UCL
  • positive regulation of oocyte development Source: MGI
  • regulation of cGMP metabolic process Source: MGI
  • relaxation of cardiac muscle Source: BHF-UCL
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cGMP, cGMP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.4.35. 3474.
ReactomeiR-MMU-418457. cGMP effects.
UniPathwayiUPA00763; UER00748.

Names & Taxonomyi

Protein namesi
Recommended name:
cGMP-specific 3',5'-cyclic phosphodiesterase (EC:3.1.4.35By similarity)
Alternative name(s):
cGMP-binding cGMP-specific phosphodiesterase
Short name:
CGB-PDE
Gene namesi
Name:Pde5a
Synonyms:Pde5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2651499. Pde5a.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988241 – 865cGMP-specific 3',5'-cyclic phosphodiesteraseAdd BLAST865

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei92PhosphoserineSequence analysis1

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

Proteomic databases

MaxQBiQ8CG03.
PaxDbiQ8CG03.
PeptideAtlasiQ8CG03.
PRIDEiQ8CG03.

PTM databases

iPTMnetiQ8CG03.
PhosphoSitePlusiQ8CG03.

Expressioni

Gene expression databases

BgeeiENSMUSG00000053965.
CleanExiMM_PDE5A.
ExpressionAtlasiQ8CG03. baseline and differential.
GenevisibleiQ8CG03. MM.

Interactioni

Protein-protein interaction databases

IntActiQ8CG03. 1 interactor.
MINTiMINT-4106875.
STRINGi10090.ENSMUSP00000069011.

Structurei

Secondary structure

1865
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi158 – 166Combined sources9
Turni167 – 171Combined sources5
Beta strandi173 – 183Combined sources11
Turni184 – 186Combined sources3
Beta strandi187 – 197Combined sources11
Turni204 – 206Combined sources3
Beta strandi207 – 209Combined sources3
Beta strandi212 – 214Combined sources3
Turni215 – 217Combined sources3
Helixi219 – 226Combined sources8
Beta strandi230 – 233Combined sources4
Beta strandi238 – 240Combined sources3
Helixi245 – 249Combined sources5
Beta strandi256 – 263Combined sources8
Turni264 – 266Combined sources3
Beta strandi267 – 275Combined sources9
Helixi287 – 300Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K31NMR-A154-320[»]
ProteinModelPortaliQ8CG03.
SMRiQ8CG03.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8CG03.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini154 – 304GAF 1Add BLAST151
Domaini336 – 493GAF 2Add BLAST158

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni578 – 843CatalyticBy similarityAdd BLAST266

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

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000007068.
HOVERGENiHBG101207.
InParanoidiQ8CG03.
KOiK13762.
OMAiTREHDAN.
OrthoDBiEOG091G04JU.
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.

Q8CG03-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERAGPNSVR SQQQRDPDWV EAWLDDHRDF TFSYFIRKAT RDMVNAWFSE
60 70 80 90 100
RVHNIPVCKE GIRAHTESCS CSLQQSPHAD NTTPGAPARK ISASEFDRPL
110 120 130 140 150
RPIVVKDSEG TVSFLSDSGK KEQMPLTPPR FDSDEGDQCS RLLELVKDIS
160 170 180 190 200
SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSKDKFL 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 IVDEDCPDSF SRVFHMECEE VGKPSDPLTR EQDANKINYM
410 420 430 440 450
YAQYVKNTME PLNIPDVTKD KRFPWTNENM GHVNTPCIGS LLCTPIKNGK
460 470 480 490 500
KNKVIGVCQL VNKMEENTGK IKAFNQNDEQ FLEAFVIFCG LGIQNTQMYE
510 520 530 540 550
AVERAMAKQM VTLEVLSYHA SAAEEETREL QALSAAVVPS AQTLKITDFS
560 570 580 590 600
FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV
610 620 630 640 650
AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LETLALLIAA LSHDLDHRGV
660 670 680 690 700
NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIDEYK
710 720 730 740 750
TTLKIIKQAI LATDLALYIK RRGEFFELIR KNQFSFEDPL QKELFLAMLM
760 770 780 790 800
TACDLSAITK PWPIQQRIAE LVAAEFFDQG DRERKELNME PADLMNREKK
810 820 830 840 850
NKIPSMQVGF IDAICLQLYE ALTHVSEDCL PLLDGCRKNR QKWQALAEQQ
860
EKMLLNGESS QGKRD
Length:865
Mass (Da):98,407
Last modified:July 27, 2011 - v2
Checksum:iBADD21CC6B62045E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti176S → T in AAN17330 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF541937 mRNA. Translation: AAN17330.1.
CH466532 Genomic DNA. Translation: EDL12317.1.
BC119137 mRNA. Translation: AAI19138.1.
BC120486 mRNA. Translation: AAI20487.1.
CCDSiCCDS17812.1.
RefSeqiNP_700471.2. NM_153422.2.
UniGeneiMm.134911.

Genome annotation databases

EnsembliENSMUST00000066728; ENSMUSP00000069011; ENSMUSG00000053965.
GeneIDi242202.
KEGGimmu:242202.
UCSCiuc008ret.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF541937 mRNA. Translation: AAN17330.1.
CH466532 Genomic DNA. Translation: EDL12317.1.
BC119137 mRNA. Translation: AAI19138.1.
BC120486 mRNA. Translation: AAI20487.1.
CCDSiCCDS17812.1.
RefSeqiNP_700471.2. NM_153422.2.
UniGeneiMm.134911.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K31NMR-A154-320[»]
ProteinModelPortaliQ8CG03.
SMRiQ8CG03.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8CG03. 1 interactor.
MINTiMINT-4106875.
STRINGi10090.ENSMUSP00000069011.

PTM databases

iPTMnetiQ8CG03.
PhosphoSitePlusiQ8CG03.

Proteomic databases

MaxQBiQ8CG03.
PaxDbiQ8CG03.
PeptideAtlasiQ8CG03.
PRIDEiQ8CG03.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000066728; ENSMUSP00000069011; ENSMUSG00000053965.
GeneIDi242202.
KEGGimmu:242202.
UCSCiuc008ret.2. mouse.

Organism-specific databases

CTDi8654.
MGIiMGI:2651499. Pde5a.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000007068.
HOVERGENiHBG101207.
InParanoidiQ8CG03.
KOiK13762.
OMAiTREHDAN.
OrthoDBiEOG091G04JU.
TreeFamiTF316499.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
BRENDAi3.1.4.35. 3474.
ReactomeiR-MMU-418457. cGMP effects.

Miscellaneous databases

ChiTaRSiPde5a. mouse.
EvolutionaryTraceiQ8CG03.
PROiQ8CG03.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000053965.
CleanExiMM_PDE5A.
ExpressionAtlasiQ8CG03. baseline and differential.
GenevisibleiQ8CG03. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE5A_MOUSE
AccessioniPrimary (citable) accession number: Q8CG03
Secondary accession number(s): Q0VBW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 112 of the entry and version 2 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, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.