cGMP-dependent 3',5'-cyclic phosphodiesterase

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P14099 (PDE2A_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 98. History...

Clusters with 100%, 90%, 50% identity |

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Third-party data

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
cGMP-dependent 3',5'-cyclic phosphodiesterase
EC=3.1.4.17

Alternative name(s):
Cyclic GMP-stimulated phosphodiesterase
Short name=CGS-PDE
Short name=cGSPDE

Gene names

Name:

PDE2A

Organism

Bos taurus (Bovine) [Reference proteome]

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	921 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes By similarity.
Catalytic activity	Nucleoside 3',5'-cyclic phosphate + H₂O = nucleoside 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.
Subunit structure	Homodimer.
Subcellular location	Membrane; Peripheral membrane protein Potential.
Domain	GAF 1 functions as a dimerization domain, whereas GAF 2 binds cGMP, which causes activation of the catalytic activity of the enzyme By similarity.
Miscellaneous	cGMP binds at an allosteric activator site By similarity.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE2 subfamily. Contains 2 GAF domains.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Metal-binding Nucleotide-binding cAMP cGMP cGMP-binding
Molecular function	Hydrolase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	GMP catabolic process Traceable author statement Ref.1. Source: AgBase cAMP catabolic process Inferred from sequence or structural similarity. Source: UniProtKB cAMP-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB cGMP catabolic process Inferred from sequence or structural similarity. Source: UniProtKB cGMP-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB cellular response to cGMP Inferred from sequence or structural similarity. Source: UniProtKB cellular response to drug Inferred from sequence or structural similarity. Source: UniProtKB cellular response to granulocyte macrophage colony-stimulating factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB cellular response to mechanical stimulus Inferred from sequence or structural similarity. Source: UniProtKB establishment of endothelial barrier Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cAMP biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein import into nucleus, translocation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of vascular permeability Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of vascular permeability Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial matrix Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB presynaptic membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	cGMP binding Inferred from sequence or structural similarity. Source: UniProtKB cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Inferred from direct assay PubMed 15210692. Source: UniProtKB drug binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist.

Isoform PDE2A1 (identifier: P14099-1) 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 PDE2A2 (identifier: P14099-3) The sequence of this isoform is not available.

Isoform PDE2A3 (identifier: P14099-2) The sequence of this isoform differs from the canonical sequence as follows: 1-25: MRRQPAASRDLFAQEPVPPGSGDGA → MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPPPQPCADS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 921

921

cGMP-dependent 3',5'-cyclic phosphodiesterase

PRO_0000198795

Regions

Domain

220 – 357

138

GAF 1

Domain

389 – 528

140

GAF 2

Region

613 – 871

259

Catalytic

Region

636 – 640

Substrate binding By similarity

Sites

Active site

636

Proton donor By similarity

Metal binding

640

Divalent metal cation 1 By similarity

Metal binding

676

Divalent metal cation 1 By similarity

Metal binding

677

Divalent metal cation 1 By similarity

Metal binding

677

Divalent metal cation 2 By similarity

Metal binding

788

Divalent metal cation 1 By similarity

Binding site

411

cGMP By similarity

Binding site

426

cGMP By similarity

Binding site

479

cGMP By similarity

Binding site

677

Substrate By similarity

Binding site

788

Substrate By similarity

Amino acid modifications

Modified residue

N-acetylmethionine Ref.3

Natural variations

Alternative sequence

1 – 25

MRRQP…SGDGA → MGQACGHSILCRSQQYPAAR PAEPRGQQVFLKPDEPPPPP QPCADS in isoform PDE2A3.

VSP_004555

Experimental info

Sequence conflict

204

N → D in AAA87353. Ref.2

Sequence conflict

633

P → L AA sequence Ref.4

Sequences

Sequence

Length

Mass (Da)

Tools

Isoform PDE2A1 [UniParc].

Last modified December 1, 1992. Version 2.
Checksum: E29F4C9875E83640
Show »

FASTA

921

103,228

        10         20         30         40         50         60 
MRRQPAASRD LFAQEPVPPG SGDGALQDAL LSLGSVIDVA GLQQAVKEAL SAVLPKVETV 

        70         80         90        100        110        120 
YTYLLDGESR LVCEEPPHEL PQEGKVREAV ISRKRLGCNG LGPSDLPGKP LARLVAPLAP 

       130        140        150        160        170        180 
DTQVLVIPLV DKEAGAVAAV ILVHCGQLSD NEEWSLQAVE KHTLVALKRV QALQQRESSV 

       190        200        210        220        230        240 
APEATQNPPE EAAGDQKGGV AYTNQDRKIL QLCGELYDLD ASSLQLKVLQ YLQQETQASR 

       250        260        270        280        290        300 
CCLLLVSEDN LQLSCKVIGD KVLEEEISFP LTTGRLGQVV EDKKSIQLKD LTSEDMQQLQ 

       310        320        330        340        350        360 
SMLGCEVQAM LCVPVISRAT DQVVALACAF NKLGGDLFTD QDEHVIQHCF HYTSTVLTST 

       370        380        390        400        410        420 
LAFQKEQKLK CECQALLQVA KNLFTHLDDV SVLLQEIITE ARNLSNAEIC SVFLLDQNEL 

       430        440        450        460        470        480 
VAKVFDGGVV EDESYEIRIP ADQGIAGHVA TTGQILNIPD AYAHPLFYRG VDDSTGFRTR 

       490        500        510        520        530        540 
NILCFPIKNE NQEVIGVAEL VNKINGPWFS KFDEDLATAF SIYCGISIAH SLLYKKVNEA 

       550        560        570        580        590        600 
QYRSHLANEM MMYHMKVSDD EYTKLLHDGI QPVAAIDSNF ASFTYTPRSL PEDDTSMAIL 

       610        620        630        640        650        660 
SMLQDMNFIN NYKIDCPTLA RFCLMVKKGY RDPPYHNWMH AFSVSHFCYL LYKNLELTNY 

       670        680        690        700        710        720 
LEDMEIFALF ISCMCHDLDH RGTNNSFQVA SKSVLAALYS SEGSVMERHH FAQAIAILNT 

       730        740        750        760        770        780 
HGCNIFDHFS RKDYQRMLDL MRDIILATDL AHHLRIFKDL QKMAEVGYDR TNKQHHSLLL 

       790        800        810        820        830        840 
CLLMTSCDLS DQTKGWKTTR KIAELIYKEF FSQGDLEKAM GNRPMEMMDR EKAYIPELQI 

       850        860        870        880        890        900 
SFMEHIAMPI YKLLQDLFPK AAELYERVAS NREHWTKVSH KFTIRGLPSN NSLDFLDEEY 

       910        920 
EVPDLDGARA PINGCCSLDA E

« Hide

Isoform PDE2A2 (Sequence not available).

–

Isoform PDE2A3 [UniParc].

Checksum: C2EC7D62C1C3F993
Show »

FASTA

942

105,575

        10         20         30         40         50         60 
MGQACGHSIL CRSQQYPAAR PAEPRGQQVF LKPDEPPPPP QPCADSLQDA LLSLGSVIDV 

        70         80         90        100        110        120 
AGLQQAVKEA LSAVLPKVET VYTYLLDGES RLVCEEPPHE LPQEGKVREA VISRKRLGCN 

       130        140        150        160        170        180 
GLGPSDLPGK PLARLVAPLA PDTQVLVIPL VDKEAGAVAA VILVHCGQLS DNEEWSLQAV 

       190        200        210        220        230        240 
EKHTLVALKR VQALQQRESS VAPEATQNPP EEAAGDQKGG VAYTNQDRKI LQLCGELYDL 

       250        260        270        280        290        300 
DASSLQLKVL QYLQQETQAS RCCLLLVSED NLQLSCKVIG DKVLEEEISF PLTTGRLGQV 

       310        320        330        340        350        360 
VEDKKSIQLK DLTSEDMQQL QSMLGCEVQA MLCVPVISRA TDQVVALACA FNKLGGDLFT 

       370        380        390        400        410        420 
DQDEHVIQHC FHYTSTVLTS TLAFQKEQKL KCECQALLQV AKNLFTHLDD VSVLLQEIIT 

       430        440        450        460        470        480 
EARNLSNAEI CSVFLLDQNE LVAKVFDGGV VEDESYEIRI PADQGIAGHV ATTGQILNIP 

       490        500        510        520        530        540 
DAYAHPLFYR GVDDSTGFRT RNILCFPIKN ENQEVIGVAE LVNKINGPWF SKFDEDLATA 

       550        560        570        580        590        600 
FSIYCGISIA HSLLYKKVNE AQYRSHLANE MMMYHMKVSD DEYTKLLHDG IQPVAAIDSN 

       610        620        630        640        650        660 
FASFTYTPRS LPEDDTSMAI LSMLQDMNFI NNYKIDCPTL ARFCLMVKKG YRDPPYHNWM 

       670        680        690        700        710        720 
HAFSVSHFCY LLYKNLELTN YLEDMEIFAL FISCMCHDLD HRGTNNSFQV ASKSVLAALY 

       730        740        750        760        770        780 
SSEGSVMERH HFAQAIAILN THGCNIFDHF SRKDYQRMLD LMRDIILATD LAHHLRIFKD 

       790        800        810        820        830        840 
LQKMAEVGYD RTNKQHHSLL LCLLMTSCDL SDQTKGWKTT RKIAELIYKE FFSQGDLEKA 

       850        860        870        880        890        900 
MGNRPMEMMD REKAYIPELQ ISFMEHIAMP IYKLLQDLFP KAAELYERVA SNREHWTKVS 

       910        920        930        940 
HKFTIRGLPS NNSLDFLDEE YEVPDLDGAR APINGCCSLD AE

« Hide

References

[1]	"Molecular cloning of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase cDNA. Identification and distribution of isozyme variants." Sonnenburg W.K., Mullaney P.J., Beavo J.A. J. Biol. Chem. 266:17655-17661(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A1).
[2]	Juilfs D.M., Sonnenburg W.K., Seraji S., Beavo J.A. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A3). Tissue: Brain.
[3]	"Amino acid sequence of the cyclic GMP stimulated cyclic nucleotide phosphodiesterase from bovine heart." le Trong H., Beier N., Sonnenburg W.K., Stroop S.D., Walsh K.A., Beavo J.A., Charbonneau H. Biochemistry 29:10280-10288(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 592-921. Tissue: Heart.
[4]	"Identification of a conserved domain among cyclic nucleotide phosphodiesterases from diverse species." Charbonneau H., Beier N., Walsh K.A., Beavo J.A. Proc. Natl. Acad. Sci. U.S.A. 83:9308-9312(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 613-694 AND 808-868. Tissue: Heart.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M73512 mRNA. Translation: AAA74559.1. L49503 mRNA. Translation: AAA87353.1.
IPI	IPI00706399. IPI00706917.
PIR	A40981.
RefSeq	NP_001137318.1. NM_001143846.1. NP_001243202.1. NM_001256273.1.
UniGene	Bt.4716.
3D structure databases
ProteinModelPortal	P14099.
SMR	P14099. Positions 202-542, 558-895.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000042623.
Proteomic databases
PRIDE	P14099.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	281971.
KEGG	bta:281971.
Organism-specific databases
CTD	5138.
Phylogenomic databases
eggNOG	NOG270709.
HOGENOM	HOG000007068.
HOVERGEN	HBG053540.
KO	K01120.
OrthoDB	EOG4THVS9.
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
BindingDB	P14099.
ChEMBL	CHEMBL3477.
NextBio	20805842.

Entry information

Entry name

PDE2A_BOVIN

Accession

Primary (citable) accession number: P14099
Secondary accession number(s): Q28064

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	December 1, 1992
Last modified:	April 3, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents