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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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

Enzyme regulationi

Inhibited by zaprinast.

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)
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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiR-CFA-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
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 32

Subcellular locationi

  • Cytoplasm
  • Cytoplasmcytosol

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2304402.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988221 – 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

PaxDbiO77746.

Expressioni

Tissue specificityi

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.

Interactioni

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000034752.

Chemistry databases

BindingDBiO77746.

Structurei

3D structure databases

ProteinModelPortaliO77746.
ModBaseiSearch...
MobiDBiSearch...

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.
InParanoidiO77746.
KOiK13762.
OMAiVDEDCSX.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PDE5A1 (identifier: O77746-1) [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
MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE
60 70 80 90 100
RVHTIPVCKE GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL
110 120 130 140 150
RPIVVKDSEG TVSFLADSEK KEQMPLTPPR FDNDEGDQCS RLLELVKDIS
160 170 180 190 200
SHLDVTALCH KIFLHIHGLI SADRYSLFLV CEDSSNDKFL ISRLFDVAEG
210 220 230 240 250
STLEEASNNC IRLEWNKGIV GHVAALGEPL 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 LEKLPDTLTR ERDANRINYM
410 420 430 440 450
YAQYVKNTME PLNIPDVSKD KRFPWTNENT GNVNQQCIRS LLCTPIKNGK
460 470 480 490 500
KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ FLEAFVIFCG LGIQNTQMYE
510 520 530 540 550
AVERAMAKQM VTLEVLSYHA SAAEEETKEL QSLAAAVVPS AQTLKITDFS
560 570 580 590 600
FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV
610 620 630 640 650
AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV
660 670 680 690 700
NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK
710 720 730 740 750
TTLKIIKQAI LATDLALYIK RRGEFFELIR KNQFNLEDPH QKELFLAMLM
760 770 780 790 800
TACDLSAITK PWPIQQRIAE LVATEFFDQG DRERKELNIE PADLMNREKK
810 820 830 840 850
NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR QKWQALAEQQ
860
EKTLINGESS QAKRN
Length:865
Mass (Da):98,294
Last modified:November 1, 1998 - v1
Checksum:iF20BB37B71E93BB6
GO
Isoform PDE5A2 (identifier: O77746-2) [UniParc]FASTAAdd to basket

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

Show »
Length:833
Mass (Da):94,750
Checksum:iAC03A9F087128BC3
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045901 – 40MERGS…VKKAT → MLPFGHQR in isoform PDE5A2. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB008467 mRNA. Translation: BAA33503.1.
AB008468 mRNA. Translation: BAA33504.1.
RefSeqiNP_001003188.1. NM_001003188.1. [O77746-2]
XP_005639100.1. XM_005639043.2. [O77746-1]
UniGeneiCfa.1752.

Genome annotation databases

EnsembliENSCAFT00000019808; ENSCAFP00000018375; ENSCAFG00000012472. [O77746-2]
ENSCAFT00000038959; ENSCAFP00000034752; ENSCAFG00000012472. [O77746-1]
GeneIDi403825.
KEGGicfa:403825.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB008467 mRNA. Translation: BAA33503.1.
AB008468 mRNA. Translation: BAA33504.1.
RefSeqiNP_001003188.1. NM_001003188.1. [O77746-2]
XP_005639100.1. XM_005639043.2. [O77746-1]
UniGeneiCfa.1752.

3D structure databases

ProteinModelPortaliO77746.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000034752.

Chemistry databases

BindingDBiO77746.
ChEMBLiCHEMBL2304402.

Proteomic databases

PaxDbiO77746.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000019808; ENSCAFP00000018375; ENSCAFG00000012472. [O77746-2]
ENSCAFT00000038959; ENSCAFP00000034752; ENSCAFG00000012472. [O77746-1]
GeneIDi403825.
KEGGicfa:403825.

Organism-specific databases

CTDi8654.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000007068.
HOVERGENiHBG101207.
InParanoidiO77746.
KOiK13762.
OMAiVDEDCSX.
OrthoDBiEOG091G04JU.
TreeFamiTF316499.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
ReactomeiR-CFA-418457. cGMP effects.

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_CANLF
AccessioniPrimary (citable) accession number: O77746
Secondary accession number(s): O77747
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: October 5, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

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.