Reviewed, UniProtKB/Swiss-Prot O54735 (PDE5A_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	833 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. 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.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. Contains 2 GAF domains.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Metal-binding Nucleotide-binding cGMP cGMP-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Allosteric enzyme
Gene Ontology (GO)
Biological process	nervous system development Ref.1 Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD signal transduction Inferred from electronic annotation. Source: InterPro vasodilation Inferred from expression pattern. Source: RGD
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Ref.1 Inferred from direct assay. Source: RGD cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]

Isoform PDE5A2 (identifier: O54735-1)

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.

Isoform PDE5A1 (identifier: O54735-2)

The sequence of this isoform is not available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 833	833	cGMP-specific 3',5'-cyclic phosphodiesterase		PRO_0000198825
Regions
	Domain	122 – 272	151	GAF 1
	Domain	304 – 461	158	GAF 2
	Region	546 – 811	266	Catalytic By similarity
Sites
	Active site	571	1	Proton donor By similarity
	Metal binding	575	1	Divalent metal cation 1 By similarity
	Metal binding	611	1	Divalent metal cation 1 By similarity
	Metal binding	612	1	Divalent metal cation 1 By similarity
	Metal binding	612	1	Divalent metal cation 2 By similarity
	Metal binding	722	1	Divalent metal cation 1 By similarity
	Binding site	775	1	cGMP By similarity
Amino acid modifications
	Modified residue	60	1	Phosphoserine Potential

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE5A2 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 712DC159C80CB09D	FASTA	833	94,556
	10 20 30 40 50 60 MLPFGDKTRD MVNAWFSERV HNIPVCKEGI RAHTESCSCS LPQSPHADNT TPGAPARKIS 70 80 90 100 110 120 ASEFDRPLRP IVVKDSEGTV SFLSDSGKKE QMPLTSPRFD SDEGDQCSRL LELVKDISSH 130 140 150 160 170 180 LDVTALCHKI FLHIHGLISA DRYSLFLVCE DSSKDKFLVS RLFDVAEGST LEEASNNCIR 190 200 210 220 230 240 LEWNKGIVGH VAAFGEPLNI KDAYEDPRFN AEVDQITGYK TQSILCMPIK NHREEVVGVA 250 260 270 280 290 300 QAINKKSGNG GTFTEKDEKD FAAYLAFCGI VLHNAQLYET SLLENKRNQV LLDLASLIFE 310 320 330 340 350 360 EQQSLEVILK KIAATIISFM QVQKCTIFIV DEDCPDSFSR VFQMEWEEVG KSSEPLTREH 370 380 390 400 410 420 DANKINYMYA QYVKNTMEPL NIPDVTKDNR FPWTNENMGH INTHCIRSLL CTPIKNGKKN 430 440 450 460 470 480 KVIGVCQLVN KMEEKTGKIK AFNQNDEQFL EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT 490 500 510 520 530 540 LEVLSYHASA AEEETRELQA LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL 550 560 570 580 590 600 NLVQNFQMKH EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE 610 620 630 640 650 660 TLALLIAALS HDLDHRGVNN SYIQRSEHPL AQLYCHSTME HHHFDQCLMV LNSPGNQILS 670 680 690 700 710 720 GLSIEEYKTT LKIIKQAILA TDLALYIKRR GEFFELIRKN EFSFEDPLQK ELFLAMLMTA 730 740 750 760 770 780 CDLSAITKPW PIQQRIAELV AAEFFDQGDR ERKELNMEPA DLMNREKKNK IPSMQVGFID 790 800 810 820 830 AICLQLYEAL THVSEDCLPL LDGCRKNRQK WQALADQQEK TLLNGESGQA KRD
	Isoform PDE5A1 (Sequence not available).	FASTA	–	–

References

[1]	"Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development." Kotera J., Yanaka N., Fujishige K., Imai Y., Akatsuka H., Ishizuka T., Kawashima K., Omori K. Eur. J. Biochem. 249:434-442(1997) [PubMed: 9370351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Lung.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D89093 mRNA. Translation: BAA23672.1.
IPI	IPI00328073.
RefSeq	NP_598268.1.
UniGene	Rn.10861 Rn.133138
3D structure databases
SMR	O54735. Positions 122-269, 493-818.
ModBase	Search...
Protein-protein interaction databases
STRING	O54735.
PTM databases
PhosphoSite	O54735.
Genome annotation databases
Ensembl	ENSRNOT00000019638; ENSRNOP00000019637; ENSRNOG00000014443; Rattus norvegicus. [Genome view]
GeneID	171115.
KEGG	rno:171115.
UCSC	NM_133584. rat.
Organism-specific databases
CTD	171115.
RGD	620995. Pde5a.
Phylogenomic databases
eggNOG	maNOG05677.
HOVERGEN	O54735.
InParanoid	O54735.
Enzyme and pathway databases
BRENDA	3.1.4.35. 248.
Gene expression databases
ArrayExpress	O54735.
Genevestigator	O54735.
GermOnline	ENSRNOG00000014443. Rattus norvegicus.
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...
Other Resources
NextBio	621836.

Entry information

Entry name

PDE5A_RAT

Accession

Primary (citable) accession number: O54735

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 1, 1998
Last modified:	January 19, 2010
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)