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Protein

cGMP-dependent 3',5'-cyclic phosphodiesterase

Gene

PDE2A

Organism
Bos taurus (Bovine)
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. 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.By similarity

Miscellaneous

cGMP binds at an allosteric activator site.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 sitei411cGMPBy similarity1
Binding sitei426cGMPBy similarity1
Binding sitei479cGMPBy similarity1
Active sitei636Proton donorBy similarity1
Metal bindingi640Divalent metal cation 1By similarity1
Metal bindingi676Divalent metal cation 1By similarity1
Metal bindingi677Divalent metal cation 1By similarity1
Metal bindingi677Divalent metal cation 2By similarity1
Binding sitei677SubstrateBy similarity1
Metal bindingi788Divalent metal cation 1By similarity1
Binding sitei788SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandcAMP, 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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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

Chemistry databases

ChEMBLiCHEMBL3477

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001987951 – 921cGMP-dependent 3',5'-cyclic phosphodiesteraseAdd BLAST921

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP14099
PRIDEiP14099

PTM databases

iPTMnetiP14099

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000011077

Chemistry databases

BindingDBiP14099

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JABelectron microscopy11.00B/N367-551[»]
3JBQelectron microscopy11.00C/G367-551[»]
ProteinModelPortaliP14099
SMRiP14099
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini220 – 357GAF 1Sequence analysisAdd BLAST138
Domaini389 – 528GAF 2Sequence analysisAdd BLAST140
Domaini558 – 882PDEasePROSITE-ProRule annotationAdd BLAST325

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni636 – 640Substrate 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.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
HOGENOMiHOG000007068
HOVERGENiHBG053540
InParanoidiP14099
KOiK18283

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.

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

Note: Additional isoforms seem to exist.
Isoform PDE2A1 (identifier: P14099-1) [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
MRRQPAASRD LFAQEPVPPG SGDGALQDAL LSLGSVIDVA GLQQAVKEAL
60 70 80 90 100
SAVLPKVETV YTYLLDGESR LVCEEPPHEL PQEGKVREAV ISRKRLGCNG
110 120 130 140 150
LGPSDLPGKP LARLVAPLAP DTQVLVIPLV DKEAGAVAAV ILVHCGQLSD
160 170 180 190 200
NEEWSLQAVE KHTLVALKRV QALQQRESSV APEATQNPPE EAAGDQKGGV
210 220 230 240 250
AYTNQDRKIL QLCGELYDLD ASSLQLKVLQ YLQQETQASR CCLLLVSEDN
260 270 280 290 300
LQLSCKVIGD KVLEEEISFP LTTGRLGQVV EDKKSIQLKD LTSEDMQQLQ
310 320 330 340 350
SMLGCEVQAM LCVPVISRAT DQVVALACAF NKLGGDLFTD QDEHVIQHCF
360 370 380 390 400
HYTSTVLTST LAFQKEQKLK CECQALLQVA KNLFTHLDDV SVLLQEIITE
410 420 430 440 450
ARNLSNAEIC SVFLLDQNEL VAKVFDGGVV EDESYEIRIP ADQGIAGHVA
460 470 480 490 500
TTGQILNIPD AYAHPLFYRG VDDSTGFRTR NILCFPIKNE NQEVIGVAEL
510 520 530 540 550
VNKINGPWFS KFDEDLATAF SIYCGISIAH SLLYKKVNEA QYRSHLANEM
560 570 580 590 600
MMYHMKVSDD EYTKLLHDGI QPVAAIDSNF ASFTYTPRSL PEDDTSMAIL
610 620 630 640 650
SMLQDMNFIN NYKIDCPTLA RFCLMVKKGY RDPPYHNWMH AFSVSHFCYL
660 670 680 690 700
LYKNLELTNY LEDMEIFALF ISCMCHDLDH RGTNNSFQVA SKSVLAALYS
710 720 730 740 750
SEGSVMERHH FAQAIAILNT HGCNIFDHFS RKDYQRMLDL MRDIILATDL
760 770 780 790 800
AHHLRIFKDL QKMAEVGYDR TNKQHHSLLL CLLMTSCDLS DQTKGWKTTR
810 820 830 840 850
KIAELIYKEF FSQGDLEKAM GNRPMEMMDR EKAYIPELQI SFMEHIAMPI
860 870 880 890 900
YKLLQDLFPK AAELYERVAS NREHWTKVSH KFTIRGLPSN NSLDFLDEEY
910 920
EVPDLDGARA PINGCCSLDA E
Length:921
Mass (Da):103,228
Last modified:December 1, 1992 - v2
Checksum:iE29F4C9875E83640
GO
Isoform PDE2A2 (identifier: P14099-3)
Sequence is not available
Length:
Mass (Da):
Isoform PDE2A3 (identifier: P14099-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MRRQPAASRDLFAQEPVPPGSGDGA → MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPPPQPCADS

Show »
Length:942
Mass (Da):105,575
Checksum:iC2EC7D62C1C3F993
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204N → D in AAA87353 (Ref. 2) Curated1
Sequence conflicti633P → L AA sequence (PubMed:3025833).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045551 – 25MRRQP…SGDGA → MGQACGHSILCRSQQYPAAR PAEPRGQQVFLKPDEPPPPP QPCADS in isoform PDE2A3. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M73512 mRNA Translation: AAA74559.1
L49503 mRNA Translation: AAA87353.1
PIRiA40981
RefSeqiNP_001137318.1, NM_001143846.1
NP_001243202.1, NM_001256273.1 [P14099-1]
UniGeneiBt.4716

Genome annotation databases

GeneIDi281971
KEGGibta:281971

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPDE2A_BOVIN
AccessioniPrimary (citable) accession number: P14099
Secondary accession number(s): Q28064
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: December 1, 1992
Last modified: April 25, 2018
This is version 129 of the entry and version 2 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
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Main funding by: National Institutes of Health