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Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Gene

Pde4a

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

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.By similarity

Catalytic activityi

Adenosine 3',5'-cyclic phosphate + H2O = adenosine 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

Activity regulationi

Inhibited by rolipram and diazepam.1 Publication

Pathwayi: 3',5'-cyclic AMP degradation

This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (Pde8b), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (Pde8a), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (Pde7b), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c)
This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei419Proton donorBy similarity1
Metal bindingi423Divalent metal cation 1By similarity1
Metal bindingi459Divalent metal cation 1By similarity1
Metal bindingi460Divalent metal cation 1By similarity1
Metal bindingi460Divalent metal cation 2By similarity1
Binding sitei460cAMPBy similarity1
Metal bindingi577Divalent metal cation 1By similarity1
Binding sitei577cAMPBy similarity1
Sitei580Binds AMP, but not cAMPBy similarity1
Binding sitei628cAMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi419 – 423cAMPBy similarity5

GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
  • cAMP binding Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cAMP catabolic process Source: UniProtKB-UniPathway
  • cellular response to drug Source: MGI
  • modulation of chemical synaptic transmission Source: MGI
  • regulation of cAMP-mediated signaling Source: MGI
  • regulation of protein kinase A signaling Source: MGI
  • sensory perception of smell Source: MGI
  • signal transduction Source: InterPro

Keywordsi

Molecular functionHydrolase
LigandcAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53 3474
ReactomeiR-MMU-180024 DARPP-32 events
R-MMU-418555 G alpha (s) signalling events
UniPathwayi
UPA00762;UER00747

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
Gene namesi
Name:Pde4a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:99558 Pde4a

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

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2111373

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988071 – 844cAMP-specific 3',5'-cyclic phosphodiesterase 4AAdd BLAST844

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineBy similarity1
Modified residuei147PhosphoserineCombined sources1
Modified residuei152PhosphoserineBy similarity1
Modified residuei160PhosphoserineBy similarity1
Modified residuei204PhosphoserineBy similarity1
Modified residuei333PhosphoserineCombined sources1
Cross-linki344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei672PhosphoserineBy similarity1
Modified residuei674PhosphoserineBy similarity1

Post-translational modificationi

Proteolytically cleaved by caspase-3.By similarity
Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei69 – 70Cleavage; by caspase-3By similarity2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO89084
PaxDbiO89084
PRIDEiO89084

PTM databases

iPTMnetiO89084
PhosphoSitePlusiO89084

Expressioni

Gene expression databases

BgeeiENSMUSG00000032177 Expressed in 144 organ(s), highest expression level in retina
CleanExiMM_PDE4A
ExpressionAtlasiO89084 baseline and differential
GenevisibleiO89084 MM

Interactioni

Subunit structurei

Interacts with LYN and ARRB2.By similarity

Protein-protein interaction databases

BioGridi202078, 2 interactors
IntActiO89084, 2 interactors
STRINGi10090.ENSMUSP00000037025

Structurei

3D structure databases

ProteinModelPortaliO89084
SMRiO89084
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini343 – 672PDEasePROSITE-ProRule annotationAdd BLAST330

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000118889
HOGENOMiHOG000236297
HOVERGENiHBG108239
InParanoidiO89084
KOiK13293
OMAiFAACVHD
OrthoDBiEOG091G06CD
PhylomeDBiO89084
TreeFamiTF314638

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
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 1 (identifier: O89084-1) [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
MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD
60 70 80 90 100
SAERSEPERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS
110 120 130 140 150
RRLEAENGPT PSPGRSPLDS QASPGLMLHA GAATSQRRES FLYRSDSDYD
160 170 180 190 200
MSPKTMSRNS SVASEAHGED LIVTPFAQVL ASLRNVRSNF SLLTNVPIPS
210 220 230 240 250
NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS
260 270 280 290 300
EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTP
310 320 330 340 350
RQRPFQQPPP AAVQQAQPMS QITGLKKLVH TGSLNINVPR FGVKTDQEDL
360 370 380 390 400
LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT
410 420 430 440 450
MMTYMLTLED HYHADVAYHN SLHAADVLQS THVLLATPAL DAVFTDLEIL
460 470 480 490 500
AALFAAAIHD VDHPGVSNQF LINTNSELAL MYNDESVLEN HHLAVGFKLL
510 520 530 540 550
QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA DLKTMVETKK
560 570 580 590 600
VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF
610 620 630 640 650
QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD
660 670 680 690 700
AQDILDTLED NRDWYHSAIR QSPSPTLEEE PGVLSDPALP DKFQFELTLE
710 720 730 740 750
EEDEEDSLEV PGLPCTEETL LAPHDTRAQA MEQSKVKGQS PAVVEVAESL
760 770 780 790 800
KQETASAHGA PEESAEAVGH SFSLETSILP DLRTLSPSEE AQGLLGLPSM
810 820 830 840
AAEVEAPRDH LAAMRACSAC SGTSGDNSAV ISAPGRWGSG GDPA
Length:844
Mass (Da):93,558
Last modified:March 1, 2002 - v2
Checksum:i632396C9F70E0F61
GO
Isoform 2 (identifier: O89084-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-234: Missing.
     235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ

Show »
Length:610
Mass (Da):68,190
Checksum:i280D59FE2DFD67A5
GO
Isoform 3 (identifier: O89084-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MEPPAAPSER...TGTGGGSSRR → MRSSAAPRAR...LRHPPGRCVS

Show »
Length:787
Mass (Da):87,193
Checksum:i703D813F13AB5E03
GO

Sequence cautioni

The sequence AAH27224 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti516R → K in AAF19201 (PubMed:11267656).Curated1
Sequence conflicti685S → G in AAH27224 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045631 – 234Missing in isoform 2. 2 PublicationsAdd BLAST234
Alternative sequenceiVSP_0045621 – 102MEPPA…GSSRR → MRSSAAPRARPRPPALALPL GPESLTHFSFSEEDTLRHPP GRCVS in isoform 3. 1 PublicationAdd BLAST102
Alternative sequenceiVSP_004564235 – 256WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 2. 2 PublicationsAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF142646
, AF142643, AF142644, AF142645 Genomic DNA Translation: AAF14519.1
AF142646, AF142644, AF142645 Genomic DNA Translation: AAF14520.1
AF208021 mRNA Translation: AAF19201.2
AJ297396 mRNA Translation: CAB96769.1
BC027224 mRNA Translation: AAH27224.2 Different initiation.
U97586 mRNA Translation: AAC25681.1
CCDSiCCDS22895.1 [O89084-1]
CCDS22896.1 [O89084-2]
CCDS80964.1 [O89084-3]
RefSeqiNP_062772.3, NM_019798.5 [O89084-2]
NP_899668.1, NM_183408.3 [O89084-1]
UniGeneiMm.191749

Genome annotation databases

EnsembliENSMUST00000003395; ENSMUSP00000003395; ENSMUSG00000032177 [O89084-2]
ENSMUST00000039413; ENSMUSP00000037025; ENSMUSG00000032177 [O89084-1]
ENSMUST00000115458; ENSMUSP00000111118; ENSMUSG00000032177 [O89084-3]
GeneIDi18577
KEGGimmu:18577
UCSCiuc009oki.2 mouse [O89084-1]
uc009okl.2 mouse [O89084-3]
uc009okm.2 mouse [O89084-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF142646
, AF142643, AF142644, AF142645 Genomic DNA Translation: AAF14519.1
AF142646, AF142644, AF142645 Genomic DNA Translation: AAF14520.1
AF208021 mRNA Translation: AAF19201.2
AJ297396 mRNA Translation: CAB96769.1
BC027224 mRNA Translation: AAH27224.2 Different initiation.
U97586 mRNA Translation: AAC25681.1
CCDSiCCDS22895.1 [O89084-1]
CCDS22896.1 [O89084-2]
CCDS80964.1 [O89084-3]
RefSeqiNP_062772.3, NM_019798.5 [O89084-2]
NP_899668.1, NM_183408.3 [O89084-1]
UniGeneiMm.191749

3D structure databases

ProteinModelPortaliO89084
SMRiO89084
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202078, 2 interactors
IntActiO89084, 2 interactors
STRINGi10090.ENSMUSP00000037025

Chemistry databases

ChEMBLiCHEMBL2111373

PTM databases

iPTMnetiO89084
PhosphoSitePlusiO89084

Proteomic databases

MaxQBiO89084
PaxDbiO89084
PRIDEiO89084

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003395; ENSMUSP00000003395; ENSMUSG00000032177 [O89084-2]
ENSMUST00000039413; ENSMUSP00000037025; ENSMUSG00000032177 [O89084-1]
ENSMUST00000115458; ENSMUSP00000111118; ENSMUSG00000032177 [O89084-3]
GeneIDi18577
KEGGimmu:18577
UCSCiuc009oki.2 mouse [O89084-1]
uc009okl.2 mouse [O89084-3]
uc009okm.2 mouse [O89084-2]

Organism-specific databases

CTDi5141
MGIiMGI:99558 Pde4a

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000118889
HOGENOMiHOG000236297
HOVERGENiHBG108239
InParanoidiO89084
KOiK13293
OMAiFAACVHD
OrthoDBiEOG091G06CD
PhylomeDBiO89084
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayi
UPA00762;UER00747

BRENDAi3.1.4.53 3474
ReactomeiR-MMU-180024 DARPP-32 events
R-MMU-418555 G alpha (s) signalling events

Miscellaneous databases

PROiPR:O89084
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032177 Expressed in 144 organ(s), highest expression level in retina
CleanExiMM_PDE4A
ExpressionAtlasiO89084 baseline and differential
GenevisibleiO89084 MM

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDE4A_MOUSE
AccessioniPrimary (citable) accession number: O89084
Secondary accession number(s): Q8R078
, Q9JHQ4, Q9QX48, Q9QX49, Q9QXI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: March 1, 2002
Last modified: November 7, 2018
This is version 145 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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