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O77746

- PDE5A_CANFA

UniProt

O77746 - PDE5A_CANFA

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Protein

cGMP-specific 3',5'-cyclic phosphodiesterase

Gene

PDE5A

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - 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.

Catalytic activityi

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

Cofactori

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions (By similarity).By similarity

Enzyme regulationi

Inhibited by zaprinast.

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: UniProtKB-EC
  2. cGMP binding Source: UniProtKB-KW
  3. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. cGMP catabolic process Source: UniProtKB-UniPathway
  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

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
OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
ProteomesiUP000002254: 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

  1. cytoplasm Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 865865cGMP-specific 3',5'-cyclic phosphodiesterasePRO_0000198822Add
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

Keywords - PTMi

Phosphoprotein

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.

Structurei

3D structure databases

ProteinModelPortaliO77746.
SMRiO77746. 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.
InParanoidiO77746.
KOiK13762.
OMAiHIRSLLC.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040MERGS…VKKAT → MLPFGHQR in isoform PDE5A2. 1 PublicationVSP_004590Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB008467 mRNA. Translation: BAA33503.1.
AB008468 mRNA. Translation: BAA33504.1.
RefSeqiNP_001003188.1. NM_001003188.1. [O77746-2]
XP_005639100.1. XM_005639043.1. [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:
EMBL
GenBank
DDBJ
Links Updated
AB008467 mRNA. Translation: BAA33503.1 .
AB008468 mRNA. Translation: BAA33504.1 .
RefSeqi NP_001003188.1. NM_001003188.1. [O77746-2 ]
XP_005639100.1. XM_005639043.1. [O77746-1 ]
UniGenei Cfa.1752.

3D structure databases

ProteinModelPortali O77746.
SMRi O77746. Positions 154-301, 525-850.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9615.ENSCAFP00000034752.

Chemistry

ChEMBLi CHEMBL2304402.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSCAFT00000019808 ; ENSCAFP00000018375 ; ENSCAFG00000012472 . [O77746-2 ]
ENSCAFT00000038959 ; ENSCAFP00000034752 ; ENSCAFG00000012472 . [O77746-1 ]
GeneIDi 403825.
KEGGi cfa:403825.

Organism-specific databases

CTDi 8654.

Phylogenomic databases

eggNOGi NOG270709.
GeneTreei ENSGT00760000119066.
HOGENOMi HOG000007068.
HOVERGENi HBG101207.
InParanoidi O77746.
KOi K13762.
OMAi HIRSLLC.
OrthoDBi EOG7RRF69.
TreeFami TF316499.

Enzyme and pathway databases

UniPathwayi UPA00763 ; UER00748 .

Miscellaneous databases

NextBioi 20817321.

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. "Novel alternative splice variants of cGMP-binding cGMP-specific phosphodiesterase."
    Kotera J., Fujishige K., Akatsuka H., Imai Y., Yanaka N., Omori K.
    J. Biol. Chem. 273:26982-26990(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE5A1 AND PDE5A2).
    Tissue: Lung.

Entry informationi

Entry nameiPDE5A_CANFA
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 29, 2014
This is version 99 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

External Data

Dasty 3