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O89084 (PDE4A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A

EC=3.1.4.53
Gene names
Name:Pde4a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length844 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

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 regulation

Inhibited by rolipram and diazepam. Ref.2

Pathway

Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Subunit structure

Interacts with LYN and ARRB2 By similarity.

Subcellular location

Cytoplasmperinuclear region By similarity.

Post-translational modification

Proteolytically cleaved by caspase-3 By similarity.

Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation By similarity.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Sequence caution

The sequence AAH27224.2 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O89084-1)

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.
Isoform 2 (identifier: O89084-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-234: Missing.
     235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ
Isoform 3 (identifier: O89084-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4A
PRO_0000198807

Regions

Nucleotide binding419 – 4235cAMP By similarity
Region317 – 710394Catalytic By similarity

Sites

Active site4191Proton donor By similarity
Metal binding4231Divalent metal cation 1 By similarity
Metal binding4591Divalent metal cation 1 By similarity
Metal binding4601Divalent metal cation 1 By similarity
Metal binding4601Divalent metal cation 2 By similarity
Metal binding5771Divalent metal cation 1 By similarity
Binding site4601cAMP By similarity
Binding site5771cAMP By similarity
Binding site6281cAMP By similarity
Site69 – 702Cleavage; by caspase-3 By similarity
Site5801Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue1471Phosphoserine; by MAPKAPK2 By similarity
Modified residue1601Phosphoserine By similarity
Cross-link344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 234234Missing in isoform 2.
VSP_004563
Alternative sequence1 – 102102MEPPA…GSSRR → MRSSAAPRARPRPPALALPL GPESLTHFSFSEEDTLRHPP GRCVS in isoform 3.
VSP_004562
Alternative sequence235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 2.
VSP_004564

Experimental info

Sequence conflict5161R → K in AAF19201. Ref.2
Sequence conflict6851S → G in AAH27224. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2002. Version 2.
Checksum: 632396C9F70E0F61

FASTA84493,558
        10         20         30         40         50         60 
MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD SAERSEPERS 

        70         80         90        100        110        120 
PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS RRLEAENGPT PSPGRSPLDS 

       130        140        150        160        170        180 
QASPGLMLHA GAATSQRRES FLYRSDSDYD MSPKTMSRNS SVASEAHGED LIVTPFAQVL 

       190        200        210        220        230        240 
ASLRNVRSNF SLLTNVPIPS NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL 

       250        260        270        280        290        300 
ETMQTYRSVS EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTP 

       310        320        330        340        350        360 
RQRPFQQPPP AAVQQAQPMS QITGLKKLVH TGSLNINVPR FGVKTDQEDL LAQELENLSK 

       370        380        390        400        410        420 
WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT MMTYMLTLED HYHADVAYHN 

       430        440        450        460        470        480 
SLHAADVLQS THVLLATPAL DAVFTDLEIL AALFAAAIHD VDHPGVSNQF LINTNSELAL 

       490        500        510        520        530        540 
MYNDESVLEN HHLAVGFKLL QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA 

       550        560        570        580        590        600 
DLKTMVETKK VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF 

       610        620        630        640        650        660 
QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD AQDILDTLED 

       670        680        690        700        710        720 
NRDWYHSAIR QSPSPTLEEE PGVLSDPALP DKFQFELTLE EEDEEDSLEV PGLPCTEETL 

       730        740        750        760        770        780 
LAPHDTRAQA MEQSKVKGQS PAVVEVAESL KQETASAHGA PEESAEAVGH SFSLETSILP 

       790        800        810        820        830        840 
DLRTLSPSEE AQGLLGLPSM AAEVEAPRDH LAAMRACSAC SGTSGDNSAV ISAPGRWGSG 


GDPA 

« Hide

Isoform 2 [UniParc].

Checksum: 280D59FE2DFD67A5
Show »

FASTA61068,190
Isoform 3 [UniParc].

Checksum: 703D813F13AB5E03
Show »

FASTA78787,193

References

« Hide 'large scale' references
[1]"Physical mapping and promoter structure of the murine cAMP-specific phosphodiesterase pde4a gene."
Olsen A.E., Bolger G.B.
Mamm. Genome 11:41-45(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
Tissue: Embryonic stem cell.
[2]"Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse."
Cherry J.A., Thompson B.E., Pho V.
Biochim. Biophys. Acta 1518:27-35(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ENZYME REGULATION.
Strain: Swiss Webster.
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: FVB/N.
Tissue: Salivary gland.
[4]"Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2."
Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.
Biochem. J. 333:693-703(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 248-355 (ISOFORM 2).
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF142646 expand/collapse EMBL AC list , 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.
RefSeqNP_062772.3. NM_019798.5.
NP_899668.1. NM_183408.3.
XP_006510155.1. XM_006510092.1.
UniGeneMm.191749.

3D structure databases

ProteinModelPortalO89084.
SMRO89084. Positions 254-696.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4996302.

Chemistry

BindingDBO89084.
ChEMBLCHEMBL2111373.

PTM databases

PhosphoSiteO89084.

Proteomic databases

PaxDbO89084.
PRIDEO89084.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003395; ENSMUSP00000003395; ENSMUSG00000032177. [O89084-2]
ENSMUST00000039413; ENSMUSP00000037025; ENSMUSG00000032177. [O89084-1]
ENSMUST00000115458; ENSMUSP00000111118; ENSMUSG00000032177. [O89084-3]
GeneID18577.
KEGGmmu:18577.
UCSCuc009oki.2. mouse. [O89084-1]
uc009okl.2. mouse. [O89084-3]
uc009okm.2. mouse. [O89084-2]

Organism-specific databases

CTD5141.
MGIMGI:99558. Pde4a.

Phylogenomic databases

eggNOGNOG122287.
GeneTreeENSGT00740000115148.
HOGENOMHOG000236297.
HOVERGENHBG108239.
InParanoidO89084.
KOK01120.
OMAPSPTMKD.
OrthoDBEOG7HQNBC.
PhylomeDBO89084.
TreeFamTF314638.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressO89084.
BgeeO89084.
CleanExMM_PDE4A.
GenevestigatorO89084.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294438.
PROO89084.
SOURCESearch...

Entry information

Entry namePDE4A_MOUSE
AccessionPrimary (citable) accession number: O89084
Secondary accession number(s): Q8R078 expand/collapse secondary AC list , Q9JHQ4, Q9QX48, Q9QX49, Q9QXI8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: March 1, 2002
Last modified: April 16, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot