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Protein

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

Gene

Pde4a

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

Functioni

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

Catalytic activityi

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

Cofactori

a divalent metal cationHMP:Note: 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.HMP:

Enzyme 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 4A (Pde4a), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (Pde8b), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (Pde8a), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (Pde7b)
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 donorHMP:1
Metal bindingi423Divalent metal cation 1HMP:1
Metal bindingi459Divalent metal cation 1HMP:1
Metal bindingi460Divalent metal cation 1HMP:1
Metal bindingi460Divalent metal cation 2HMP:1
Binding sitei460cAMPHMP:1
Metal bindingi577Divalent metal cation 1HMP:1
Binding sitei577cAMPHMP:1
Sitei580Binds AMP, but not cAMPHMP:1
Binding sitei628cAMPHMP:1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi419 – 423cAMPHMP:5

GO - Molecular functioni

GO - Biological processi

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.
UniPathwayiUPA00762; 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 residuei13PhosphoserineHMP:1
Modified residuei147PhosphoserineND:1
Modified residuei152PhosphoserineHMP:1
Modified residuei160PhosphoserineHMP:1
Modified residuei204PhosphoserineHMP:1
Modified residuei333PhosphoserineND:1
Cross-linki344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)HMP:
Modified residuei672PhosphoserineHMP:1
Modified residuei674PhosphoserineHMP:1

Post-translational modificationi

Proteolytically cleaved by caspase-3.HMP:
Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.HMP:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei69 – 70Cleavage; by caspase-3HMP:2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO89084.
PaxDbiO89084.
PRIDEiO89084.

PTM databases

iPTMnetiO89084.
PhosphoSitePlusiO89084.

Expressioni

Gene expression databases

BgeeiENSMUSG00000032177.
CleanExiMM_PDE4A.
ExpressionAtlasiO89084. baseline and differential.
GenevisibleiO89084. MM.

Interactioni

Subunit structurei

Interacts with LYN and ARRB2.HMP:

Protein-protein interaction databases

MINTiMINT-4996302.
STRINGi10090.ENSMUSP00000037025.

Structurei

3D structure databases

ProteinModelPortaliO89084.
SMRiO89084.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni317 – 710CatalyticHMP:Add BLAST394

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiO89084.
KOiK13293.
OMAiGPQFQPM.
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 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.IKR:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti516R → K in AAF19201 (PubMed:11267656).IKR:1
Sequence conflicti685S → G in AAH27224 (PubMed:15489334).IKR:1

Alternative sequence

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

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: October 25, 2017
This is version 137 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families