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Protein

cGMP-dependent 3',5'-cyclic phosphodiesterase

Gene

Pde2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate.

Cofactori

a divalent metal cationBy similarityNote: 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei407cGMP1 Publication1
Binding sitei422cGMP1 Publication1
Binding sitei475cGMP1 Publication1
Active sitei632Proton donorBy similarity1
Metal bindingi636Divalent metal cation 1By similarity1
Metal bindingi672Divalent metal cation 1By similarity1
Metal bindingi673Divalent metal cation 1By similarity1
Metal bindingi673Divalent metal cation 2By similarity1
Binding sitei673SubstrateBy similarity1
Metal bindingi784Divalent metal cation 1By similarity1
Binding sitei784SubstrateBy similarity1

GO - Molecular functioni

  • cAMP binding Source: UniProtKB
  • cGMP binding Source: UniProtKB
  • cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
  • cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
  • drug binding Source: UniProtKB
  • GAF domain binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • TPR domain binding Source: MGI

GO - Biological processi

  • aorta development Source: MGI
  • cAMP catabolic process Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cardiac septum development Source: MGI
  • cellular response to cGMP Source: UniProtKB
  • cellular response to drug Source: UniProtKB
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to macrophage colony-stimulating factor stimulus Source: UniProtKB
  • cellular response to mechanical stimulus Source: UniProtKB
  • cGMP catabolic process Source: UniProtKB
  • cGMP-mediated signaling Source: UniProtKB
  • coronary vasculature development Source: MGI
  • establishment of endothelial barrier Source: UniProtKB
  • heart development Source: MGI
  • heart valve development Source: MGI
  • metabolic process Source: UniProtKB
  • negative regulation of cAMP biosynthetic process Source: UniProtKB
  • negative regulation of protein import into nucleus, translocation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of vascular permeability Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of vascular permeability Source: UniProtKB
  • protein targeting to mitochondrion Source: UniProtKB
  • regulation of cGMP metabolic process Source: MGI
  • ventricular septum development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:Pde2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2446107. Pde2a.

Subcellular locationi

GO - Cellular componenti

  • axon Source: MGI
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • dendrite Source: MGI
  • endoplasmic reticulum Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • presynaptic membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001987971 – 916cGMP-dependent 3',5'-cyclic phosphodiesteraseAdd BLAST916

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei97PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ922S4.
PaxDbiQ922S4.
PeptideAtlasiQ922S4.
PRIDEiQ922S4.

PTM databases

iPTMnetiQ922S4.
PhosphoSitePlusiQ922S4.
SwissPalmiQ922S4.

Expressioni

Gene expression databases

CleanExiMM_PDE2A.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • GAF domain binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • TPR domain binding Source: MGI

Protein-protein interaction databases

IntActiQ922S4. 2 interactors.
STRINGi10090.ENSMUSP00000131553.

Structurei

Secondary structure

1916
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi199 – 210Combined sources12
Helixi217 – 231Combined sources15
Beta strandi234 – 242Combined sources9
Beta strandi244 – 246Combined sources3
Beta strandi248 – 254Combined sources7
Beta strandi257 – 271Combined sources15
Helixi272 – 278Combined sources7
Helixi284 – 286Combined sources3
Helixi289 – 299Combined sources11
Beta strandi306 – 312Combined sources7
Turni314 – 316Combined sources3
Beta strandi318 – 330Combined sources13
Helixi337 – 381Combined sources45
Turni382 – 384Combined sources3
Turni386 – 388Combined sources3
Helixi389 – 401Combined sources13
Beta strandi403 – 411Combined sources9
Beta strandi413 – 421Combined sources9
Helixi440 – 448Combined sources9
Beta strandi452 – 455Combined sources4
Helixi468 – 471Combined sources4
Beta strandi478 – 484Combined sources7
Beta strandi490 – 499Combined sources10
Beta strandi502 – 504Combined sources3
Helixi507 – 535Combined sources29

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MC0X-ray2.86A190-549[»]
ProteinModelPortaliQ922S4.
SMRiQ922S4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ922S4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini216 – 353GAF 1Add BLAST138
Domaini385 – 524GAF 2Add BLAST140

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni609 – 867CatalyticBy similarityAdd BLAST259
Regioni632 – 636Substrate bindingBy similarity5

Domaini

GAF 1 functions as a dimerization domain, whereas GAF 2 binds cGMP, which causes activation of the catalytic activity of the enzyme.1 Publication

Sequence similaritiesi

Contains 2 GAF domains.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
HOGENOMiHOG000007068.
HOVERGENiHBG053540.
InParanoidiQ922S4.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 1 hit.
PF13185. GAF_2. 1 hit.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 3 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q922S4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRVSAASQD PLAQKPEPPG SRDDRLEDAL LSLGAVIDIA GLRQAARDAL
60 70 80 90 100
SAVLPKVETV YTYLLDGESR LVCEDPPHEL PQEGKIREAV ISQKRLSCNG
110 120 130 140 150
LGPSDLLGKP LARLVAPLAP DMQVLVIPLL DKETGSVAAV ILVHCGQLSD
160 170 180 190 200
SEEQSLQVVE KHALVALRRV QALQQRRPEA VQNTSVDASE DQKDEKGYTD
210 220 230 240 250
HDRKILQLCG ELFDLDATSL QLKVLQYLQQ ETQATHCCLL LVSEDNLQLS
260 270 280 290 300
CKVIGDKVLG EEVSFPLTMG RLGQVVEDKQ CIQLKDLTSD DVQQLQNMLG
310 320 330 340 350
CELQAMLCVP VISRATDQVV ALACAFNKLG GDFFTDEDEH VIQHCFHYTG
360 370 380 390 400
TVLTSTLAFQ KEQKLKCECQ ALLQVAKNLF THLDDVSVLL QEIITEARNL
410 420 430 440 450
SNAEICSVFL LDQNELVAKV FDGGVVDDES YEIRIPADQG IAGHVATTGQ
460 470 480 490 500
ILNIPDAYAH PLFYRGVDDS TGFRTRNILC FPIKNENQEV IGVAELVNKI
510 520 530 540 550
NGPWFSKFDE DLATAFSIYC GISIAHSLLY KKVNEAQYRS HLANEMMMYH
560 570 580 590 600
MKVSDDEYTK LLHDGIQPVA AIDSNFANFT YTPRSLPEDD TSMAILSMLQ
610 620 630 640 650
DMNFINNYKI DCPTLARFCL MVKKGYRDPP YHNWMHAFSV SHFCYLLYKN
660 670 680 690 700
LELSNYLEDI EIFALFISCM CHDLDHRGTN NSFQVASKSV LAALYSSEGS
710 720 730 740 750
VMERHHFAQA IAILNTHGCN IFDHFSRKDY QRMLDLMRDI ILATDLAHHL
760 770 780 790 800
RIFKDLQKMA EVGYDRNNRQ HHRLLLCLLM TSCDLSDQTK GWKTTRKIAE
810 820 830 840 850
LIYKEFFSQG DLEKAMGNRP MEMMDREKAY IPELQISFME HIAMPIYKLL
860 870 880 890 900
QDLFPKAAEL YERVASNREH WTKVSHKFTI RGLPSNNSLD FLDEEYEVPD
910
LDGTRAPVNG CCSLEG
Length:916
Mass (Da):103,249
Last modified:July 27, 2011 - v3
Checksum:iA386C6773CC4F5B4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4 – 5VS → QP in BC057029 (PubMed:15489334).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129079 Genomic DNA. No translation available.
AC129609 Genomic DNA. No translation available.
BC006845 mRNA. Translation: AAH06845.1.
BC029810 mRNA. Translation: AAH29810.1.
BC057029 mRNA. No translation available.
UniGeneiMm.247564.

Genome annotation databases

UCSCiuc009ioq.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129079 Genomic DNA. No translation available.
AC129609 Genomic DNA. No translation available.
BC006845 mRNA. Translation: AAH06845.1.
BC029810 mRNA. Translation: AAH29810.1.
BC057029 mRNA. No translation available.
UniGeneiMm.247564.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MC0X-ray2.86A190-549[»]
ProteinModelPortaliQ922S4.
SMRiQ922S4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ922S4. 2 interactors.
STRINGi10090.ENSMUSP00000131553.

PTM databases

iPTMnetiQ922S4.
PhosphoSitePlusiQ922S4.
SwissPalmiQ922S4.

Proteomic databases

MaxQBiQ922S4.
PaxDbiQ922S4.
PeptideAtlasiQ922S4.
PRIDEiQ922S4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiuc009ioq.3. mouse.

Organism-specific databases

MGIiMGI:2446107. Pde2a.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
HOGENOMiHOG000007068.
HOVERGENiHBG053540.
InParanoidiQ922S4.

Miscellaneous databases

EvolutionaryTraceiQ922S4.
PROiQ922S4.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PDE2A.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 1 hit.
PF13185. GAF_2. 1 hit.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 3 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE2A_MOUSE
AccessioniPrimary (citable) accession number: Q922S4
Secondary accession number(s): Q8K2U1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

cGMP binds at an allosteric activator site.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.