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P14099 (PDE2A_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length921 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentMembrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandcAMP
cGMP
cGMP-binding
Metal-binding
Nucleotide-binding
   Molecular functionHydrolase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processGMP 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

metabolic process

Inferred from direct assay PubMed 15210692. Source: GOC

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

regulation of cAMP metabolic process

Traceable author statement Ref.1. Source: AgBase

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

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_functioncGMP binding

Inferred from sequence or structural similarity. Source: UniProtKB

cGMP-stimulated cyclic-nucleotide phosphodiesterase activity

Inferred from direct assay PubMed 15210692. Source: UniProtKB

cyclic-nucleotide phosphodiesterase activity

Inferred from sequence or structural similarity. 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 921921cGMP-dependent 3',5'-cyclic phosphodiesterase
PRO_0000198795

Regions

Domain220 – 357138GAF 1
Domain389 – 528140GAF 2
Region613 – 871259Catalytic
Region636 – 6405Substrate binding By similarity

Sites

Active site6361Proton donor By similarity
Metal binding6401Divalent metal cation 1 By similarity
Metal binding6761Divalent metal cation 1 By similarity
Metal binding6771Divalent metal cation 1 By similarity
Metal binding6771Divalent metal cation 2 By similarity
Metal binding7881Divalent metal cation 1 By similarity
Binding site4111cGMP By similarity
Binding site4261cGMP By similarity
Binding site4791cGMP By similarity
Binding site6771Substrate By similarity
Binding site7881Substrate By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.3

Natural variations

Alternative sequence1 – 2525MRRQP…SGDGA → MGQACGHSILCRSQQYPAAR PAEPRGQQVFLKPDEPPPPP QPCADS in isoform PDE2A3.
VSP_004555

Experimental info

Sequence conflict2041N → D in AAA87353. Ref.2
Sequence conflict6331P → L AA sequence Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE2A1 [UniParc].

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

FASTA921103,228
        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 »

FASTA942105,575

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.
PIRA40981.
RefSeqNP_001137318.1. NM_001143846.1.
NP_001243202.1. NM_001256273.1.
UniGeneBt.4716.

3D structure databases

ProteinModelPortalP14099.
SMRP14099. Positions 202-542, 558-895.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000042623.

Chemistry

BindingDBP14099.
ChEMBLCHEMBL3477.

Proteomic databases

PRIDEP14099.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID281971.
KEGGbta:281971.

Organism-specific databases

CTD5138.

Phylogenomic databases

eggNOGNOG270709.
HOGENOMHOG000007068.
HOVERGENHBG053540.
KOK01120.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003018. GAF.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20805842.

Entry information

Entry namePDE2A_BOVIN
AccessionPrimary (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 16, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families