Reviewed, UniProtKB/Swiss-Prot Q28156 (PDE5A_BOVIN)

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

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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.
Catalytic activity	Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.
Cofactor	Binds 2 divalent metal cations per subunit By similarity. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
Enzyme regulation	Most potently inhibited by zaprinast and dipyridamole.
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.
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	cGMP catabolic process Inferred from sequence or structural similarity. Source: AgBase signal transduction Inferred from electronic annotation. Source: InterPro
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Inferred from sequence or structural similarity. Source: AgBase cGMP binding Inferred from sequence or structural similarity. Source: AgBase magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW zinc 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_0000198821

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

Mutagenesis

276

1

N → A: Decreased cGMP-binding; no change in catalytic activity. Ref.4

Mutagenesis

277

1

K → A: Decreased cGMP-binding; no change in catalytic activity. Ref.4

Mutagenesis

277

1

K → R: Slight increase in cGMP-binding. Ref.4

Mutagenesis

289

1

D → A: Decreased cGMP-binding; no change in catalytic activity. Ref.4 Ref.3 Ref.5

Mutagenesis

289

1

D → N: Increased cGMP-binding; no change in catalytic activity. Ref.4 Ref.3 Ref.5

Mutagenesis

290

1

E → A: No change in cGMP-binding. Ref.4

Mutagenesis

478

1

D → A: Increased cGMP-binding; no change in catalytic activity. Phosphorylated at lower concentrations of cGMP. Ref.3 Ref.5

Secondary structure

1

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865

Helix Strand Turn

Details...

Turn

125 – 127

3

Helix

135 – 149

15

Turn

155 – 157

3

Helix

158 – 170

13

Beta strand

173 – 180

8

Turn

186 – 188

3

Beta strand

189 – 192

4

Beta strand

194 – 197

4

Beta strand

211 – 214

4

Helix

218 – 226

9

Beta strand

230 – 233

4

Beta strand

235 – 237

3

Beta strand

249 – 251

3

Beta strand

254 – 266

13

Beta strand

268 – 275

8

Helix

278 – 280

3

Helix

287 – 302

16

Sequences

	Sequence		Length	Mass (Da)
	Q28156-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 2FF7144B2990B4F7	FASTA	865	98,627
	10 20 30 40 50 60 MERAGPGSAR PQQQWDQDSV EAWLDDHWDF TFSYFVRKGT REMVNAWFAE RVHTIPVCKE 70 80 90 100 110 120 GIKGHTESCS CPLQPSPRAE SSVPGTPTRK ISASEFDRPL RPIVIKDSEG TVSFLSDSDK 130 140 150 160 170 180 KEQMPLTSPR FDNDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV 190 200 210 220 230 240 CEDSSNDKFL 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 IVDEDCSDSF SSVFHMECEE LEKSSDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD 430 440 450 460 470 480 KRFPWTNENM GNINQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEETTGK VKAFNRNDEQ 490 500 510 520 530 540 FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL QSLAAAVVPS 550 560 570 580 590 600 AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCKWIL SVKKNYRKNV 610 620 630 640 650 660 AYHNWRHAFN TAQCMFAALK AGKIQKRLTD LEILALLIAA LSHDLDHRGV NNSYIQRSEH 670 680 690 700 710 720 PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI LATDLALYIK 730 740 750 760 770 780 RRGEFFELIM KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE LVATEFFDQG 790 800 810 820 830 840 DRERKELNIE PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR 850 860 QKWQALAEQQ EKTLINGESS QTKRN

References

[1]	"The structure of a bovine lung cGMP-binding, cGMP-specific phosphodiesterase deduced from a cDNA clone." McAllister-Lucas L.M., Sonnenburg W.K., Kadlecek A., Seger D., Trong H.L., Colbran J.L., Thomas M.K., Walsh K.A., Francis S.H., Corbin J.D., Beavo J.A. J. Biol. Chem. 268:22863-22873(1993) [PubMed: 8226796] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 4-16; 39-55; 90-101; 127-138; 390-409 AND 531-539. Tissue: Lung.
[2]	"Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase." Francis S.H., Colbran J.L., McAllister-Lucas L.M., Corbin J.D. J. Biol. Chem. 269:22477-22480(1994) [PubMed: 8077192] [Abstract] Cited for: METAL-BINDING.
[3]	"An essential aspartic acid at each of two allosteric cGMP-binding sites of a cGMP-specific phosphodiesterase." McAllister-Lucas L.M., Haik T.L., Colbran J.L., Sonnenburg W.K., Seger D., Turko I.V., Beavo J.A., Francis S.H., Corbin J.D. J. Biol. Chem. 270:30671-30679(1995) [PubMed: 8530505] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-289 AND ASP-478.
[4]	"Identification of key amino acids in a conserved cGMP-binding site of cGMP-binding phosphodiesterases. A putative NKXnD motif for cGMP binding." Turko I.V., Haik T.L., McAllister-Lucas L.M., Burns F., Francis S.H., Corbin J.D. J. Biol. Chem. 271:22240-22244(1996) [PubMed: 8703039] [Abstract] Cited for: MUTAGENESIS OF ASN-276; LYS-277; ASP-289 AND GLU-290.
[5]	"Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation." Turko I.V., Francis S.H., Corbin J.D. Biochem. J. 329:505-510(1998) [PubMed: 9445376] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF ASP-289 AND ASP-478.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L16545 mRNA. Translation: AAB00990.1.

IPI

IPI00710965.

RefSeq

NP_776842.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FL4	model	-	A	118-309	[»]

SMR

Q28156. Positions 154-301, 525-850.

ModBase

Search...

Protein-protein interaction databases

STRING

Q28156.

Genome annotation databases

Ensembl

ENSBTAT00000014479; ENSBTAP00000014479; ENSBTAG00000024888; Bos taurus. [Genome view]

GeneID

281972.

KEGG

bta:281972.

Organism-specific databases

CTD

281972.

Phylogenomic databases

eggNOG

maNOG05677.

HOVERGEN

Q28156.

InParanoid

Q28156.

OMA

TPPRFDN.

OrthoDB

EOG9CVJSV.

Enzyme and pathway databases

BRENDA

3.1.4.35. 251.

Family and domain databases

InterPro

IPR003018. GAF.
IPR003607. Metal-dep_PHydrolase_HD_dom.
IPR002073. PDEase.
[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...

Entry information

Entry name

PDE5A_BOVIN

Accession

Primary (citable) accession number: Q28156

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)