O77746 (PDE5A_CANFA) 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

Canis familiaris (Dog) (Canis lupus familiaris)

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length	865 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.
Enzyme regulation	Inhibited by zaprinast.
Pathway	Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.
Subcellular location	Cytoplasm. Cytoplasm › cytosol. Note: PDE5A1 and PDE5A2 are located mostly to soluble cellular fractions and some to particulate cellular fractions.
Tissue specificity	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.
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.
Miscellaneous	cGMP-binding to the allosteric sites is stimulated by 3-isobutyl-1-methylxanthine (IBMX).
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. Contains 2 GAF domains.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Metal-binding Nucleotide-binding cGMP cGMP-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Inferred from electronic annotation. Source: EC cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform PDE5A1 (identifier: O77746-1)

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 PDE5A2 (identifier: O77746-2)

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

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_0000198822
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
Natural variations
	Alternative sequence	1 – 40	40	MERGS…VKKAT → MLPFGHQR in isoform PDE5A2.		VSP_004590

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE5A1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: F20BB37B71E93BB6	FASTA	865	98,294
	10 20 30 40 50 60 MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE RVHTIPVCKE 70 80 90 100 110 120 GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL RPIVVKDSEG TVSFLADSEK 130 140 150 160 170 180 KEQMPLTPPR FDNDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV 190 200 210 220 230 240 CEDSSNDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAALGEPL 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 LEKLPDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD 430 440 450 460 470 480 KRFPWTNENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ 490 500 510 520 530 540 FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETKEL QSLAAAVVPS 550 560 570 580 590 600 AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV 610 620 630 640 650 660 AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV NNSYIQRSEH 670 680 690 700 710 720 PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI LATDLALYIK 730 740 750 760 770 780 RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE LVATEFFDQG 790 800 810 820 830 840 DRERKELNIE PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR 850 860 QKWQALAEQQ EKTLINGESS QAKRN
	Isoform PDE5A2 [UniParc]. Checksum: AC03A9F087128BC3	FASTA	833	94,750
	10 20 30 40 50 60 MLPFGHQRRE MVNAWFAERV HTIPVCKEGI RGHAESCSCS SQQSSRADSS APGTPTRKIS 70 80 90 100 110 120 ASEFDRPLRP IVVKDSEGTV SFLADSEKKE QMPLTPPRFD NDEGDQCSRL LELVKDISSH 130 140 150 160 170 180 LDVTALCHKI FLHIHGLISA DRYSLFLVCE DSSNDKFLIS RLFDVAEGST LEEASNNCIR 190 200 210 220 230 240 LEWNKGIVGH VAALGEPLNI 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 DEDCSDSFSS VFHMECEELE KLPDTLTRER 370 380 390 400 410 420 DANRINYMYA QYVKNTMEPL NIPDVSKDKR FPWTNENTGN VNQQCIRSLL CTPIKNGKKN 430 440 450 460 470 480 KVIGVCQLVN KMEENTGKVK PFNRNDEQFL EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT 490 500 510 520 530 540 LEVLSYHASA AEEETKELQS LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL 550 560 570 580 590 600 NLVQNFQMKH EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE 610 620 630 640 650 660 ILALLIAALS HDLDHRGVNN SYIQRSEHPL AQLYCHSIME HHHFDQCLMI LNSPGNQILS 670 680 690 700 710 720 GLSIEEYKTT LKIIKQAILA TDLALYIKRR GEFFELIRKN QFNLEDPHQK ELFLAMLMTA 730 740 750 760 770 780 CDLSAITKPW PIQQRIAELV ATEFFDQGDR ERKELNIEPA DLMNREKKNK IPSMQVGFID 790 800 810 820 830 AICLQLYEAL THVSEDCFPL LDGCRKNRQK WQALAEQQEK TLINGESSQA KRN

References

[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: 9756948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE5A1 AND PDE5A2). Tissue: Lung.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB008467 mRNA. Translation: BAA33503.1. AB008468 mRNA. Translation: BAA33504.1.
RefSeq	NP_001003188.1. NM_001003188.1.
UniGene	Cfa.44716.
3D structure databases
ProteinModelPortal	O77746.
SMR	O77746. Positions 154-301, 525-850.
ModBase	Search...
Protein-protein interaction databases
STRING	O77746.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	403825.
KEGG	cfa:403825.
Organism-specific databases
CTD	8654.
Phylogenomic databases
eggNOG	maNOG05677.
GeneTree	ENSGT00550000074280.
HOVERGEN	HBG101207.
InParanoid	O77746.
OrthoDB	EOG4WSW90.
Family and domain databases
InterPro	IPR003018. GAF. IPR003607. Metal-dep_PHydrolase_HD_dom. IPR023088. PDEase. IPR002073. PDEase_catalytic_dom. IPR023174. PDEase_CS. [Graphical view]
Gene3D	G3DSA:1.10.1300.10. PDEase_catalytic_dom. 1 hit.
KO	K13762.
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_CANFA

Accession

Primary (citable) accession number: O77746
Secondary accession number(s): O77747

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program