Q8CG03 (PDE5A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Pde5a
Synonyms:	Pde5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	865 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Catalytic activity	Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.
Cofactor	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.
Pathway	Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.
Domain	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.
Post-translational modification	Phosphorylation is regulated by binding of cGMP to the two allosteric sites By similarity. Phosphorylation by PRKG1 leads to its activation By similarity.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. Contains 2 GAF domains.

Ontologies

Keywords
Domain	Repeat
Ligand	Metal-binding Nucleotide-binding cGMP cGMP-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cGMP catabolic process Inferred from direct assay PubMed 12554648. Source: MGI negative regulation of T cell proliferation Inferred from mutant phenotype PubMed 17101732. Source: MGI negative regulation of cardiac muscle contraction Inferred from mutant phenotype PubMed 19127022. Source: BHF-UCL positive regulation of G-protein coupled receptor protein signaling pathway Inferred by curator PubMed 19127022. Source: BHF-UCL positive regulation of MAP kinase activity Inferred from mutant phenotype PubMed 19127022. Source: BHF-UCL positive regulation of cardiac muscle hypertrophy Inferred from mutant phenotype PubMed 19127022. Source: BHF-UCL positive regulation of oocyte development Inferred from mutant phenotype PubMed 19474061. Source: MGI relaxation of cardiac muscle Inferred from mutant phenotype PubMed 19127022. Source: BHF-UCL signal transduction Inferred from electronic annotation. Source: InterPro
Molecular_function	3',5'-cyclic-GMP phosphodiesterase activity Inferred from electronic annotation. Source: EC 3',5'-cyclic-nucleotide phosphodiesterase activity Inferred from mutant phenotype PubMed 19474061. Source: MGI cGMP binding Inferred from direct assay PubMed 12554648PubMed 18534985. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 865

865

cGMP-specific 3',5'-cyclic phosphodiesterase

PRO_0000198824

Regions

Domain

154 – 304

151

GAF 1

Domain

336 – 493

158

GAF 2

Region

578 – 843

266

Catalytic By similarity

Sites

Active site

603

1

Proton donor By similarity

Metal binding

607

1

Divalent metal cation 1 By similarity

Metal binding

643

1

Divalent metal cation 1 By similarity

Metal binding

644

1

Divalent metal cation 1 By similarity

Metal binding

644

1

Divalent metal cation 2 By similarity

Metal binding

754

1

Divalent metal cation 1 By similarity

Binding site

807

1

cGMP By similarity

Amino acid modifications

Modified residue

92

1

Phosphoserine Potential

Experimental info

Sequence conflict

176

1

S → T in AAN17330. Ref.1

Secondary structure

1

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865

Helix Strand Turn

Details...

Helix

158 – 166

9

Turn

167 – 171

5

Beta strand

173 – 183

11

Turn

184 – 186

3

Beta strand

187 – 197

11

Turn

204 – 206

3

Beta strand

207 – 209

3

Beta strand

212 – 214

3

Turn

215 – 217

3

Helix

219 – 226

8

Beta strand

230 – 233

4

Beta strand

238 – 240

3

Helix

245 – 249

5

Beta strand

256 – 263

8

Turn

264 – 266

3

Beta strand

267 – 275

9

Helix

287 – 300

14

Sequences

	Sequence		Length	Mass (Da)
	Q8CG03 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: BADD21CC6B62045E	FASTA	865	98,407
	10 20 30 40 50 60 MERAGPNSVR SQQQRDPDWV EAWLDDHRDF TFSYFIRKAT RDMVNAWFSE RVHNIPVCKE 70 80 90 100 110 120 GIRAHTESCS CSLQQSPHAD NTTPGAPARK ISASEFDRPL RPIVVKDSEG TVSFLSDSGK 130 140 150 160 170 180 KEQMPLTPPR FDSDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV 190 200 210 220 230 240 CEDSSKDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAAFGEPL NIKDAYEDPR 250 260 270 280 290 300 FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC 310 320 330 340 350 360 GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS FMQVQKCTIF 370 380 390 400 410 420 IVDEDCPDSF SRVFHMECEE VGKPSDPLTR EQDANKINYM YAQYVKNTME PLNIPDVTKD 430 440 450 460 470 480 KRFPWTNENM GHVNTPCIGS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK IKAFNQNDEQ 490 500 510 520 530 540 FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL QALSAAVVPS 550 560 570 580 590 600 AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV 610 620 630 640 650 660 AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LETLALLIAA LSHDLDHRGV NNSYIQRSEH 670 680 690 700 710 720 PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIDEYK TTLKIIKQAI LATDLALYIK 730 740 750 760 770 780 RRGEFFELIR KNQFSFEDPL QKELFLAMLM TACDLSAITK PWPIQQRIAE LVAAEFFDQG 790 800 810 820 830 840 DRERKELNME PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCL PLLDGCRKNR 850 860 QKWQALAEQQ EKMLLNGESS QGKRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Burns F., Sonnenburg W.K., Rybalkin S.D., Beavo J.A. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF541937 mRNA. Translation: AAN17330.1.
CH466532 Genomic DNA. Translation: EDL12317.1.
BC119137 mRNA. Translation: AAI19138.1.
BC120486 mRNA. Translation: AAI20487.1.

IPI

IPI00229355.

RefSeq

NP_700471.2. NM_153422.2.

UniGene

Mm.134911.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K31	NMR	-	A	154-320	[»]

ProteinModelPortal

Q8CG03.

SMR

Q8CG03. Positions 89-850.

ModBase

Search...

PTM databases

PhosphoSite

Q8CG03.

Proteomic databases

PaxDb

Q8CG03.

PRIDE

Q8CG03.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000066728; ENSMUSP00000069011; ENSMUSG00000053965.

GeneID

242202.

KEGG

mmu:242202.

Organism-specific databases

CTD

8654.

MGI

MGI:2651499. Pde5a.

Phylogenomic databases

eggNOG

NOG270709.

GeneTree

ENSGT00690000102141.

HOGENOM

HOG000007068.

HOVERGEN

HBG101207.

InParanoid

Q0VBW0.

KO

K13762.

OMA

REHDANK.

OrthoDB

EOG4WSW90.

Enzyme and pathway databases

UniPathway

UPA00763; UER00748.

Gene expression databases

Bgee

Q8CG03.

CleanEx

MM_PDE5A.

Genevestigator

Q8CG03.

Family and domain databases

Gene3D

1.10.1300.10. 1 hit.

InterPro

IPR003018. GAF.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]

Pfam

PF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]

PRINTS

PR00387. PDIESTERASE1.

SMART

SM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]

PROSITE

PS00126. PDEASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PDE5A. mouse.

EvolutionaryTrace

Q8CG03.

NextBio

385258.

SOURCE

Search...

Entry information

Entry name

PDE5A_MOUSE

Accession

Primary (citable) accession number: Q8CG03
Secondary accession number(s): Q0VBW0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program