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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

Pde5a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. 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. High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (Pde9a), cGMP-specific 3',5'-cyclic phosphodiesterase (Pde5a), 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 sitei571Proton donorBy similarity1
Metal bindingi575Zinc; via tele nitrogenBy similarity1
Metal bindingi611Zinc; via tele nitrogenBy similarity1
Metal bindingi612MagnesiumBy similarity1
Metal bindingi612ZincBy similarity1
Metal bindingi722ZincBy similarity1
Binding sitei775cGMPBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cGMP catabolic process Source: UniProtKB-UniPathway
  • nervous system development Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of chronic inflammatory response Source: RGD
  • positive regulation of vasoconstriction Source: RGD
  • regulation of the force of heart contraction Source: RGD
  • response to hypoxia Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to testosterone Source: RGD
  • short-term memory Source: RGD
  • signal transduction Source: InterPro
  • vasodilation Source: RGD
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. 5301.
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620995. Pde5a.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
Complete GO annotation...

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4567.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988251 – 833cGMP-specific 3',5'-cyclic phosphodiesteraseAdd BLAST833

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60PhosphoserineSequence 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

PaxDbiO54735.
PRIDEiO54735.

PTM databases

iPTMnetiO54735.
PhosphoSitePlusiO54735.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019637.

Chemistry databases

BindingDBiO54735.

Structurei

3D structure databases

ProteinModelPortaliO54735.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini122 – 272GAF 1Add BLAST151
Domaini304 – 461GAF 2Add BLAST158

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni546 – 811CatalyticBy 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.
HOGENOMiHOG000007068.
HOVERGENiHBG101207.
InParanoidiO54735.
KOiK13762.
PhylomeDBiO54735.

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. AlignAdd to basket

Isoform PDE5A2 (identifier: O54735-1) [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

        10         20         30         40         50
MLPFGDKTRD MVNAWFSERV HNIPVCKEGI RAHTESCSCS LPQSPHADNT
60 70 80 90 100
TPGAPARKIS ASEFDRPLRP IVVKDSEGTV SFLSDSGKKE QMPLTSPRFD
110 120 130 140 150
SDEGDQCSRL LELVKDISSH LDVTALCHKI FLHIHGLISA DRYSLFLVCE
160 170 180 190 200
DSSKDKFLVS RLFDVAEGST LEEASNNCIR LEWNKGIVGH VAAFGEPLNI
210 220 230 240 250
KDAYEDPRFN AEVDQITGYK TQSILCMPIK NHREEVVGVA QAINKKSGNG
260 270 280 290 300
GTFTEKDEKD FAAYLAFCGI VLHNAQLYET SLLENKRNQV LLDLASLIFE
310 320 330 340 350
EQQSLEVILK KIAATIISFM QVQKCTIFIV DEDCPDSFSR VFQMEWEEVG
360 370 380 390 400
KSSEPLTREH DANKINYMYA QYVKNTMEPL NIPDVTKDNR FPWTNENMGH
410 420 430 440 450
INTHCIRSLL CTPIKNGKKN KVIGVCQLVN KMEEKTGKIK AFNQNDEQFL
460 470 480 490 500
EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT LEVLSYHASA AEEETRELQA
510 520 530 540 550
LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL NLVQNFQMKH
560 570 580 590 600
EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE
610 620 630 640 650
TLALLIAALS HDLDHRGVNN SYIQRSEHPL AQLYCHSTME HHHFDQCLMV
660 670 680 690 700
LNSPGNQILS GLSIEEYKTT LKIIKQAILA TDLALYIKRR GEFFELIRKN
710 720 730 740 750
EFSFEDPLQK ELFLAMLMTA CDLSAITKPW PIQQRIAELV AAEFFDQGDR
760 770 780 790 800
ERKELNMEPA DLMNREKKNK IPSMQVGFID AICLQLYEAL THVSEDCLPL
810 820 830
LDGCRKNRQK WQALADQQEK TLLNGESGQA KRD
Length:833
Mass (Da):94,556
Last modified:June 1, 1998 - v1
Checksum:i712DC159C80CB09D
GO
Isoform PDE5A1 (identifier: O54735-2)
Sequence is not available
Length:
Mass (Da):

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89093 mRNA. Translation: BAA23672.1.
RefSeqiNP_598268.1. NM_133584.1. [O54735-1]
UniGeneiRn.10861.
Rn.133138.

Genome annotation databases

GeneIDi171115.
KEGGirno:171115.
UCSCiRGD:620995. rat. [O54735-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89093 mRNA. Translation: BAA23672.1.
RefSeqiNP_598268.1. NM_133584.1. [O54735-1]
UniGeneiRn.10861.
Rn.133138.

3D structure databases

ProteinModelPortaliO54735.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019637.

Chemistry databases

BindingDBiO54735.
ChEMBLiCHEMBL4567.

PTM databases

iPTMnetiO54735.
PhosphoSitePlusiO54735.

Proteomic databases

PaxDbiO54735.
PRIDEiO54735.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi171115.
KEGGirno:171115.
UCSCiRGD:620995. rat. [O54735-1]

Organism-specific databases

CTDi8654.
RGDi620995. Pde5a.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
HOGENOMiHOG000007068.
HOVERGENiHBG101207.
InParanoidiO54735.
KOiK13762.
PhylomeDBiO54735.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
BRENDAi3.1.4.35. 5301.

Miscellaneous databases

PROiO54735.

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_RAT
AccessioniPrimary (citable) accession number: O54735
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 2, 2016
This is version 119 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

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

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.