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P54748 (PDE4A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. 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
Alternative name(s):
DPDE2
Gene names
Name:Pde4a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length844 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.

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.

Tissue specificity

Isoform 2 is testis specific.

Post-translational modification

Proteolytically cleaved by caspase-3 By similarity.

Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54748-1)

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: P54748-2)

Also known as: PDE4A8;

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MEPPAAPSER...TGTGGGSSRR → MPSRKRLTLPRIFIVRKNGNS
Isoform 3 (identifier: P54748-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-234: Missing.
     235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ
Isoform 4 (identifier: P54748-4)

Also known as: Medium;

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: Missing.
Isoform 5 (identifier: P54748-5)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-318: Missing.
     354-386: Missing.
Isoform 6 (identifier: P54748-6)

Also known as: PDE4A10;

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MEPPAAPSER...TGTGGGSSRR → ALPLGPESLTHFSFSEEDTLRHPPGRCVS
Note: Incomplete sequence.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4A
PRO_0000198808

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 Ref.6
Modified residue1601Phosphoserine By similarity
Cross-link344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 318318Missing in isoform 5.
VSP_004569
Alternative sequence1 – 259259Missing in isoform 4.
VSP_004568
Alternative sequence1 – 234234Missing in isoform 3.
VSP_004566
Alternative sequence1 – 102102MEPPA…GSSRR → MPSRKRLTLPRIFIVRKNGN S in isoform 2.
VSP_004565
Alternative sequence1 – 102102MEPPA…GSSRR → ALPLGPESLTHFSFSEEDTL RHPPGRCVS in isoform 6.
VSP_038187
Alternative sequence235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 3.
VSP_004567
Alternative sequence354 – 38633Missing in isoform 5.
VSP_004570

Experimental info

Mutagenesis1471S → A: Abolishes phosphorylation by MAPKAPK2. Ref.6
Mutagenesis1611S → A: Does not affect phosphorylation by MAPKAPK2. Ref.6
Sequence conflict1301A → R in AAF14352. Ref.5
Sequence conflict465 – 4662GV → AL in AAA41848. Ref.4
Sequence conflict465 – 4662GV → AL in AAA41823. Ref.4
Sequence conflict603 – 6042GD → AH in AAA41848. Ref.4
Sequence conflict603 – 6042GD → AH in AAA41823. Ref.4
Sequence conflict8331A → T in AAC37699. Ref.1
Sequence conflict8331A → T in AAA41101. Ref.1
Sequence conflict8331A → T in AAA41102. Ref.1
Sequence conflict8331A → T in AAF14352. Ref.5

Secondary structure

...... 844
Helix Strand Turn

Details...

Sequences

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

Last modified October 1, 1996. Version 1.
Checksum: 1A5F5101E4DBF1B6

FASTA84493,439
        10         20         30         40         50         60 
MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYPD SAERSETERS 

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

       130        140        150        160        170        180 
QASPGLVLHA GATTSQRRES FLYRSDSDYD MSPKAVSRSS SVASEAHAED LIVTPFAQVL 

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

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

       310        320        330        340        350        360 
RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL LAQELENLSK 

       370        380        390        400        410        420 
WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT MMMYMLTLED 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 QSPSPPLEEE PGGLGHPSLP DKFQFELTLE EEEEEDSLEV PGLPTTEETF 

       730        740        750        760        770        780 
LAAEDARAQA VDWSKVKGPS TTVVEVAERL KQETASAYGA PQESMEAVGC SFSPGTPILP 

       790        800        810        820        830        840 
DVRTLSSSEE APGLLGLPST AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG 


GDPA 

« Hide

Isoform 2 (PDE4A8) [UniParc].

Checksum: 9E1E33481260566A
Show »

FASTA76384,647
Isoform 3 [UniParc].

Checksum: FE439ACE95E1D1AC
Show »

FASTA61068,161
Isoform 4 (Medium) [UniParc].

Checksum: 3A188A286A28E174
Show »

FASTA58565,059
Isoform 5 (Short) [UniParc].

Checksum: 53735B34F1122F97
Show »

FASTA49354,526
Isoform 6 (PDE4A10) [UniParc].

Checksum: C1DB345199B5D59C
Show »

FASTA77185,344

References

[1]"Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene."
Davis R.L., Takayasu H., Eberwine M., Myres J.
Proc. Natl. Acad. Sci. U.S.A. 86:3604-3608(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5).
[2]"Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases."
Bolger G.B., Rodgers L., Riggs M.
Gene 149:237-244(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
Tissue: Brain.
[3]"Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts. Characterization of a novel tissue-specific isoform, RNPDE4A8."
Bolger G.B., McPhee I., Houslay M.D.
J. Biol. Chem. 271:1065-1071(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: Sprague-Dawley.
Tissue: Testis.
[4]"Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes."
Swinnen J.V., Joseph D.R., Conti M.
Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 319-677 (ISOFORMS 3/4).
Tissue: Testis.
[5]"Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic AMP-specific phosphodiesterase PDE4A10."
Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E., Sullivan M., Houslay M.D.
Mol. Pharmacol. 59:996-1011(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
[6]"Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation."
MacKenzie K.F., Wallace D.A., Hill E.V., Anthony D.F., Henderson D.J., Houslay D.M., Arthur J.S., Baillie G.S., Houslay M.D.
Biochem. J. 435:755-769(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-147, MUTAGENESIS OF SER-147 AND SER-161.
[7]"Determination of the structure of the N-terminal splice region of the cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and identification of the membrane association domain using chimeric constructs."
Smith K.J., Scotland G., Beattie J., Trayer I.P., Houslay M.D.
J. Biol. Chem. 271:16703-16711(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-26 OF ISOFORM 3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27057 mRNA. Translation: AAC27098.1.
L36467 mRNA. Translation: AAB00357.1.
L27062 mRNA. Translation: AAA56859.1.
M25348 mRNA. Translation: AAA41848.1.
M28411 mRNA. Translation: AAA41823.1.
M26715 mRNA. Translation: AAC37699.1.
M26716 mRNA. Translation: AAA41101.1.
M26717 mRNA. Translation: AAA41102.1.
AF110461 mRNA. Translation: AAF14352.2.
PIRI53865.
I67946.
RefSeqNP_037233.3. NM_013101.3. [P54748-1]
UniGeneRn.91357.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortalP54748.
SMRP54748. Positions 337-698.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP54748.
ChEMBLCHEMBL2094267.

PTM databases

PhosphoSiteP54748.

Proteomic databases

PaxDbP54748.
PRIDEP54748.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25638.
KEGGrno:25638.
UCSCRGD:3279. rat. [P54748-1]

Organism-specific databases

CTD5141.
RGD3279. Pde4a.

Phylogenomic databases

eggNOGNOG122287.
HOGENOMHOG000236297.
HOVERGENHBG108239.
InParanoidP54748.
KOK01120.
PhylomeDBP54748.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.

Gene expression databases

GenevestigatorP54748.

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

EvolutionaryTraceP54748.
NextBio607467.
PMAP-CutDBP54748.

Entry information

Entry namePDE4A_RAT
AccessionPrimary (citable) accession number: P54748
Secondary accession number(s): P14645, Q9EQR7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 113 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways