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Protein

cGMP-dependent 3',5'-cyclic phosphodiesterase

Gene

Pde2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
Isoform PDE2A2: Regulates mitochondrial cAMP levels and respiration (PubMed:21724846). Involved in the regulation of mitochondria morphology/dynamics and apoptotic cell death via local modulation of cAMP/PKA signaling in the mitochondrion, including the monitoring of local cAMP levels at the outer mitochondrial membrane and of PKA-dependent phosphorylation of DNM1L (PubMed:28463107).2 Publications

Miscellaneous

cGMP binds at an allosteric activator site.

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

Enzyme regulationi

Specifically inhibited by Bay 60-7550.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei430cGMPCombined sources1 Publication1
Binding sitei445cGMPCombined sources1 Publication1
Binding sitei498cGMPCombined sources1 Publication1
Active sitei655Proton donorPROSITE-ProRule annotation1
Metal bindingi659Divalent metal cation 1By similarity1
Metal bindingi695Divalent metal cation 1By similarity1
Metal bindingi696Divalent metal cation 1By similarity1
Metal bindingi696Divalent metal cation 2By similarity1
Binding sitei696SubstrateBy similarity1
Metal bindingi807Divalent metal cation 1By similarity1
Binding sitei807SubstrateBy 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
  • identical protein binding Source: MGI
  • 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 2,3,7,8-tetrachlorodibenzodioxine Source: MGI
  • cellular response to cAMP 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
  • negative regulation of cAMP-mediated signaling Source: MGI
  • negative regulation of cell death Source: UniProtKB
  • negative regulation of oxidative phosphorylation Source: UniProtKB
  • negative regulation of protein import into nucleus, translocation Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II 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
  • regulation of cGMP metabolic process Source: MGI
  • regulation of mitochondrion organization Source: UniProtKB
  • ventricular septum development Source: MGI

Keywordsi

Molecular functionHydrolase
LigandcAMP, cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-418457 cGMP effects
R-MMU-418555 G alpha (s) signalling events

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2446107 Pde2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane

Pathology & Biotechi

Disruption phenotypei

Abnormally elongated mitochondria. This phenotype is reversed by treatment with the PKA inhibitor H89. Protected from ionomycin- but not staurosporin-induced cell death.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001987972 – 939cGMP-dependent 3',5'-cyclic phosphodiesteraseAdd BLAST938

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi5S-palmitoyl cysteineBy similarity1
Lipidationi11S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Lipoprotein, Myristate, Palmitate

Proteomic databases

MaxQBiQ922S4
PaxDbiQ922S4
PeptideAtlasiQ922S4
PRIDEiQ922S4

PTM databases

iPTMnetiQ922S4
PhosphoSitePlusiQ922S4
SwissPalmiQ922S4

Expressioni

Tissue specificityi

Isoform PDE2A2: Expressed in brain and liver (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000030653
CleanExiMM_PDE2A

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

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

Protein-protein interaction databases

IntActiQ922S4, 4 interactors
STRINGi10090.ENSMUSP00000131553

Structurei

Secondary structure

1939
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi218 – 229Combined sources12
Helixi236 – 250Combined sources15
Beta strandi253 – 261Combined sources9
Beta strandi263 – 265Combined sources3
Beta strandi267 – 273Combined sources7
Beta strandi276 – 290Combined sources15
Helixi291 – 297Combined sources7
Helixi303 – 305Combined sources3
Helixi308 – 318Combined sources11
Beta strandi325 – 331Combined sources7
Turni333 – 335Combined sources3
Beta strandi337 – 349Combined sources13
Helixi360 – 404Combined sources45
Turni405 – 407Combined sources3
Turni409 – 411Combined sources3
Helixi412 – 424Combined sources13
Beta strandi426 – 434Combined sources9
Beta strandi436 – 444Combined sources9
Helixi463 – 471Combined sources9
Beta strandi475 – 478Combined sources4
Helixi491 – 494Combined sources4
Beta strandi501 – 507Combined sources7
Beta strandi513 – 522Combined sources10
Beta strandi525 – 527Combined sources3
Helixi530 – 558Combined sources29

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MC0X-ray2.86A217-561[»]
ProteinModelPortaliQ922S4
SMRiQ922S4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ922S4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 373GAF 1Sequence analysisAdd BLAST138
Domaini408 – 547GAF 2Sequence analysisAdd BLAST140
Domaini577 – 901PDEasePROSITE-ProRule annotationAdd BLAST325

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni655 – 659Substrate 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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000119066
HOGENOMiHOG000007068
HOVERGENiHBG053540
InParanoidiQ922S4
OrthoDBiEOG091G0L2F
TreeFamiTF316499

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
3.30.450.40, 2 hits
InterProiView protein in InterPro
IPR003018 GAF
IPR029016 GAF-like_dom_sf
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF01590 GAF, 1 hit
PF13185 GAF_2, 1 hit
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00065 GAF, 2 hits
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PDE2A3Curated (identifier: Q922S4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGQACGHSIL CRSQQYPAAR PAEPRGQQVF LKPDEPPPQP CADSLQDALL
60 70 80 90 100
SLGAVIDIAG LRQAARDALS AVLPKVETVY TYLLDGESRL VCEDPPHELP
110 120 130 140 150
QEGKIREAVI SQKRLSCNGL GPSDLLGKPL ARLVAPLAPD MQVLVIPLLD
160 170 180 190 200
KETGSVAAVI LVHCGQLSDS EEQSLQVVEK HALVALRRVQ ALQQRRPEAV
210 220 230 240 250
QNTSVDASED QKDEKGYTDH DRKILQLCGE LFDLDATSLQ LKVLQYLQQE
260 270 280 290 300
TQATHCCLLL VSEDNLQLSC KVIGDKVLGE EVSFPLTMGR LGQVVEDKQC
310 320 330 340 350
IQLKDLTSDD VQQLQNMLGC ELQAMLCVPV ISRATDQVVA LACAFNKLGG
360 370 380 390 400
DFPTSSFTDE DEHVIQHCFH YTGTVLTSTL AFQKEQKLKC ECQALLQVAK
410 420 430 440 450
NLFTHLDDVS VLLQEIITEA RNLSNAEICS VFLLDQNELV AKVFDGGVVD
460 470 480 490 500
DESYEIRIPA DQGIAGHVAT TGQILNIPDA YAHPLFYRGV DDSTGFRTRN
510 520 530 540 550
ILCFPIKNEN QEVIGVAELV NKINGPWFSK FDEDLATAFS IYCGISIAHS
560 570 580 590 600
LLYKKVNEAQ YRSHLANEMM MYHMKVSDDE YTKLLHDGIQ PVAAIDSNFA
610 620 630 640 650
NFTYTPRSLP EDDTSMAILS MLQDMNFINN YKIDCPTLAR FCLMVKKGYR
660 670 680 690 700
DPPYHNWMHA FSVSHFCYLL YKNLELSNYL EDIEIFALFI SCMCHDLDHR
710 720 730 740 750
GTNNSFQVAS KSVLAALYSS EGSVMERHHF AQAIAILNTH GCNIFDHFSR
760 770 780 790 800
KDYQRMLDLM RDIILATDLA HHLRIFKDLQ KMAEVGYDRN NRQHHRLLLC
810 820 830 840 850
LLMTSCDLSD QTKGWKTTRK IAELIYKEFF SQGDLEKAMG NRPMEMMDRE
860 870 880 890 900
KAYIPELQIS FMEHIAMPIY KLLQDLFPKA AELYERVASN REHWTKVSHK
910 920 930
FTIRGLPSNN SLDFLDEEYE VPDLDGTRAP VNGCCSLEG
Length:939
Mass (Da):105,619
Last modified:March 28, 2018 - v4
Checksum:i1DD7BD9DBCF806E3
GO
Isoform PDE2A1Curated (identifier: Q922S4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPQPCADSLQ → MRRQPAASQDPLAQKPEPPGSRDDRLE
     353-356: Missing.

Show »
Length:916
Mass (Da):103,288
Checksum:i51C03B086633BF20
GO
Isoform PDE2A21 Publication (identifier: Q922S4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: MGQACGHSILCRSQQYPAARPAEP → MVLVLHHILIAVVQFLR
     353-356: Missing.

Note: Contains a transit peptide at positions 1-17.1 Publication
Show »
Length:928
Mass (Da):104,676
Checksum:i63E789DD439C9481
GO

Sequence cautioni

The sequence BC057029 differs from that shown. Reason: Frameshift at position 560.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti596D → G in BAE41887 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0593961 – 46MGQAC…ADSLQ → MRRQPAASQDPLAQKPEPPG SRDDRLE in isoform PDE2A1. CuratedAdd BLAST46
Alternative sequenceiVSP_0593951 – 24MGQAC…RPAEP → MVLVLHHILIAVVQFLR in isoform PDE2A2. CuratedAdd BLAST24
Alternative sequenceiVSP_059397353 – 356Missing in isoform PDE2A1 and isoform PDE2A2. Curated4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK159012 mRNA Translation: BAE34768.1
AK170573 mRNA Translation: BAE41887.1
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.
CCDSiCCDS52330.1 [Q922S4-1]
RefSeqiNP_001137320.1, NM_001143848.2 [Q922S4-1]
NP_001137321.1, NM_001143849.2 [Q922S4-3]
XP_006507590.1, XM_006507527.3
UniGeneiMm.247564

Genome annotation databases

EnsembliENSMUST00000163751; ENSMUSP00000131553; ENSMUSG00000110195 [Q922S4-1]
GeneIDi207728
UCSCiuc009ioq.3 mouse [Q922S4-1]
uc012fqk.2 mouse

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPDE2A_MOUSE
AccessioniPrimary (citable) accession number: Q922S4
Secondary accession number(s): Q3TCR8, Q3TXZ6, Q8K2U1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: March 28, 2018
Last modified: May 23, 2018
This is version 140 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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