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O00408 (PDE2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length941 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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. Ref.7 Ref.8

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. Ref.8

Subcellular location

Cell membrane; Lipid-anchor Ref.4.

Tissue specificity

Expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas.

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 componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandcAMP
cGMP
cGMP-binding
Metal-binding
Nucleotide-binding
   Molecular functionHydrolase
   PTMLipoprotein
Myristate
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cAMP catabolic process

Inferred from direct assay Ref.7PubMed 17704206PubMed 14687666. Source: UniProtKB

cAMP-mediated signaling

Inferred from mutant phenotype PubMed 17704206. Source: UniProtKB

cGMP catabolic process

Inferred from direct assay Ref.7Ref.8PubMed 14687666. Source: UniProtKB

cGMP-mediated signaling

Inferred from mutant phenotype PubMed 17704206. Source: UniProtKB

calcium ion transmembrane transport

Traceable author statement PubMed 10375378. Source: GOC

cellular response to cGMP

Inferred from direct assay PubMed 17704206Ref.8. Source: UniProtKB

cellular response to drug

Inferred from expression pattern PubMed 14687666. Source: UniProtKB

cellular response to granulocyte macrophage colony-stimulating factor stimulus

Inferred from direct assay PubMed 14687666. Source: UniProtKB

cellular response to macrophage colony-stimulating factor stimulus

Inferred from direct assay PubMed 14687666. Source: UniProtKB

cellular response to mechanical stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to transforming growth factor beta stimulus

Inferred from expression pattern PubMed 17704206. Source: UniProtKB

establishment of endothelial barrier

Inferred from sequence or structural similarity. Source: UniProtKB

metabolic process

Inferred from direct assay PubMed 17329248. Source: UniProtKB

monocyte differentiation

Inferred from expression pattern PubMed 14687666. 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 direct assay PubMed 17329248. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17329248. Source: UniProtKB

negative regulation of vascular permeability

Inferred from mutant phenotype PubMed 17704206. Source: UniProtKB

positive regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of vascular permeability

Inferred from mutant phenotype PubMed 17704206. Source: UniProtKB

protein targeting to mitochondrion

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

axon

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 10375378PubMed 19506089. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 17329248. Source: UniProtKB

dendrite

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial matrix

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 10375378. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 10375378. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19252089. Source: UniProtKB

presynaptic membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionTPR domain binding

Inferred from physical interaction PubMed 17329248. Source: UniProtKB

cAMP binding

Inferred from mutant phenotype Ref.7. Source: UniProtKB

cGMP binding

Inferred from direct assay PubMed 17329248PubMed 19689430Ref.8. Source: UniProtKB

cGMP-stimulated cyclic-nucleotide phosphodiesterase activity

Inferred from direct assay PubMed 17329248PubMed 19689430. Source: UniProtKB

calcium channel activity

Traceable author statement PubMed 10375378. Source: UniProtKB

cyclic-nucleotide phosphodiesterase activity

Inferred from direct assay Ref.7. Source: UniProtKB

drug binding

Inferred from direct assay Ref.7. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from physical interaction Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AIPO001706EBI-1785967,EBI-704197

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform PDE2A3 (identifier: O00408-1)

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 PDE2A1 (identifier: O00408-2)

The sequence of this isoform is not available.
Note: Soluble form.
Isoform PDE2A2 (identifier: O00408-3)

The sequence of this isoform is not available.
Isoform PDE2A4 (identifier: O00408-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: MGQACGHSILCRSQQYPAARPAEP → MKKQRIQEGKSLAHR
Isoform 5 (identifier: O00408-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: MGQACGHSILCRSQQYPAARPAEP → MVLVLHHILIAVVQFLR
Note: No experimental confirmation available. Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 941940cGMP-dependent 3',5'-cyclic phosphodiesterase
PRO_0000198796

Regions

Domain241 – 377137GAF 1
Domain409 – 548140GAF 2
Region633 – 891259Catalytic By similarity
Region656 – 6605Substrate binding

Sites

Active site6561Proton donor By similarity
Metal binding6601Divalent metal cation 1
Metal binding6961Divalent metal cation 1
Metal binding6971Divalent metal cation 1
Metal binding6971Divalent metal cation 2
Metal binding8081Divalent metal cation 1
Binding site4311cGMP By similarity
Binding site4461cGMP By similarity
Binding site4991cGMP By similarity
Binding site6971Substrate
Binding site8081Substrate

Amino acid modifications

Lipidation21N-myristoyl glycine Ref.4 Ref.6
Lipidation51S-palmitoyl cysteine; in isoform PDE2A3 Probable
Lipidation111S-palmitoyl cysteine; in isoform PDE2A3 Probable

Natural variations

Alternative sequence1 – 2424MGQAC…RPAEP → MVLVLHHILIAVVQFLR in isoform 5.
VSP_054047
Alternative sequence1 – 2424MGQAC…RPAEP → MKKQRIQEGKSLAHR in isoform PDE2A4.
VSP_042213
Natural variant2241T → I.
Corresponds to variant rs341047 [ dbSNP | Ensembl ].
VAR_024170

Experimental info

Sequence conflict381P → L in AAS75513. Ref.2
Sequence conflict2131T → A in AAS75513. Ref.2
Sequence conflict6641V → A in AAS75513. Ref.2

Secondary structure

............................................................................................................. 941
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE2A3 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 9797609B487FD64E

FASTA941105,717
        10         20         30         40         50         60 
MGQACGHSIL CRSQQYPAAR PAEPRGQQVF LKPDEPPPPP QPCADSLQDA LLSLGSVIDI 

        70         80         90        100        110        120 
SGLQRAVKEA LSAVLPRVET VYTYLLDGES QLVCEDPPHE LPQEGKVREA IISQKRLGCN 

       130        140        150        160        170        180 
GLGFSDLPGK PLARLVAPLA PDTQVLVMPL ADKEAGAVAA VILVHCGQLS DNEEWSLQAV 

       190        200        210        220        230        240 
EKHTLVALRR VQVLQQRGPR EAPRAVQNPP EGTAEDQKGG AAYTDRDRKI LQLCGELYDL 

       250        260        270        280        290        300 
DASSLQLKVL QYLQQETRAS RCCLLLVSED NLQLSCKVIG DKVLGEEVSF PLTGCLGQVV 

       310        320        330        340        350        360 
EDKKSIQLKD LTSEDVQQLQ SMLGCELQAM LCVPVISRAT DQVVALACAF NKLEGDLFTD 

       370        380        390        400        410        420 
EDEHVIQHCF HYTSTVLTST LAFQKEQKLK CECQALLQVA KNLFTHLDDV SVLLQEIITE 

       430        440        450        460        470        480 
ARNLSNAEIC SVFLLDQNEL VAKVFDGGVV DDESYEIRIP ADQGIAGHVA TTGQILNIPD 

       490        500        510        520        530        540 
AYAHPLFYRG VDDSTGFRTR NILCFPIKNE NQEVIGVAEL VNKINGPWFS KFDEDLATAF 

       550        560        570        580        590        600 
SIYCGISIAH SLLYKKVNEA QYRSHLANEM MMYHMKVSDD EYTKLLHDGI QPVAAIDSNF 

       610        620        630        640        650        660 
ASFTYTPRSL PEDDTSMAIL SMLQDMNFIN NYKIDCPTLA RFCLMVKKGY RDPPYHNWMH 

       670        680        690        700        710        720 
AFSVSHFCYL LYKNLELTNY LEDIEIFALF ISCMCHDLDH RGTNNSFQVA SKSVLAALYS 

       730        740        750        760        770        780 
SEGSVMERHH FAQAIAILNT HGCNIFDHFS RKDYQRMLDL MRDIILATDL AHHLRIFKDL 

       790        800        810        820        830        840 
QKMAEVGYDR NNKQHHRLLL CLLMTSCDLS DQTKGWKTTR KIAELIYKEF FSQGDLEKAM 

       850        860        870        880        890        900 
GNRPMEMMDR EKAYIPELQI SFMEHIAMPI YKLLQDLFPK AAELYERVAS NREHWTKVSH 

       910        920        930        940 
KFTIRGLPSN NSLDFLDEEY EVPDLDGTRA PINGCCSLDA E 

« Hide

Isoform PDE2A1 (Sequence not available).
Isoform PDE2A2 (Sequence not available).
Isoform PDE2A4 [UniParc].

Checksum: 9F5CE92BA3C2E2E5
Show »

FASTA932104,955
Isoform 5 [UniParc].

Checksum: 2C1E4885AD13F504
Show »

FASTA934105,147

References

« Hide 'large scale' references
[1]"Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase."
Rosman G.J., Martins T.J., Sonnenburg W.K., Beavo J.A., Ferguson K., Loughney K.
Gene 191:89-95(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A3).
Tissue: Fetal brain and Hippocampus.
[2]"Human PDE2A4."
Bugaj-Gaweda B., De Vivo M., Wang D.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE2A4).
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes."
Russwurm C., Zoidl G., Koesling D., Russwurm M.
J. Biol. Chem. 284:25782-25790(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: MYRISTOYLATION AT GLY-2, PALMITOYLATION AT CYS-5 AND CYS-11, SUBCELLULAR LOCATION.
[5]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system."
Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E., Tsunasawa S., Utsumi T.
Proteomics 10:1780-1793(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: MYRISTOYLATION AT GLY-2.
[7]"Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system."
Iffland A., Kohls D., Low S., Luan J., Zhang Y., Kothe M., Cao Q., Kamath A.V., Ding Y.H., Ellenberger T.
Biochemistry 44:8312-8325(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 578-919 IN COMPLEX WITH METAL IONS AND PHOSPHATE, FUNCTION.
[8]"Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct."
Pandit J., Forman M.D., Fennell K.F., Dillman K.S., Menniti F.S.
Proc. Natl. Acad. Sci. U.S.A. 106:18225-18230(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 215-919 IN COMPLEX WITH METAL IONS AND THE INHIBITOR IBMX, SUBUNIT, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U67733 mRNA. Translation: AAC51320.1.
AY495087 mRNA. Translation: AAS75513.1.
AP003065 Genomic DNA. No translation available.
AP005019 Genomic DNA. No translation available.
RefSeqNP_001137311.1. NM_001143839.3.
NP_001139681.1. NM_001146209.2.
NP_001230713.1. NM_001243784.1.
NP_002590.1. NM_002599.4.
UniGeneHs.503163.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z1LX-ray1.70A578-919[»]
3IBJX-ray3.02A/B215-900[»]
3ITMX-ray2.49A/B/C/D579-919[»]
3ITUX-ray1.58A/B/C/D579-919[»]
4HTXX-ray1.90A/B/C/D578-919[»]
4HTZX-ray2.00A/B/C/D578-919[»]
4JIBX-ray1.72A/B/C/D579-919[»]
ProteinModelPortalO00408.
SMRO00408. Positions 223-916.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111164. 1 interaction.
DIPDIP-40269N.
IntActO00408. 3 interactions.
STRING9606.ENSP00000334910.

Chemistry

BindingDBO00408.
ChEMBLCHEMBL2652.
DrugBankDB00203. Sildenafil.
DB00605. Sulindac.
GuidetoPHARMACOLOGY1297.

PTM databases

PhosphoSiteO00408.

Proteomic databases

PaxDbO00408.
PRIDEO00408.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334456; ENSP00000334910; ENSG00000186642. [O00408-1]
ENST00000444035; ENSP00000411657; ENSG00000186642. [O00408-4]
ENST00000540345; ENSP00000446399; ENSG00000186642. [O00408-4]
ENST00000544570; ENSP00000442256; ENSG00000186642.
GeneID5138.
KEGGhsa:5138.
UCSCuc010rrb.2. human. [O00408-4]
uc010rrc.2. human. [O00408-1]

Organism-specific databases

CTD5138.
GeneCardsGC11M072287.
HGNCHGNC:8777. PDE2A.
HPACAB009752.
MIM602658. gene.
neXtProtNX_O00408.
PharmGKBPA33125.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270709.
HOGENOMHOG000007068.
HOVERGENHBG053540.
InParanoidO00408.
KOK01120.
OMACFHYTGT.
OrthoDBEOG767393.
PhylomeDBO00408.
TreeFamTF316499.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressO00408.
BgeeO00408.
CleanExHS_PDE2A.
GenevestigatorO00408.

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

ChiTaRSPDE2A. human.
EvolutionaryTraceO00408.
GeneWikiPDE2A.
GenomeRNAi5138.
NextBio19812.
PROO00408.
SOURCESearch...

Entry information

Entry namePDE2A_HUMAN
AccessionPrimary (citable) accession number: O00408
Secondary accession number(s): E9PGI1, F6W5Z0, Q5J793
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM