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Protein

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

Gene

Pde4a

Organism
Rattus norvegicus (Rat)
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.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

Enzyme regulationi

Inhibited by rolipram.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei69 – 702Cleavage; by caspase-3By similarity
Active sitei419 – 4191Proton donorBy similarity
Metal bindingi423 – 4231Divalent metal cation 1By similarity
Metal bindingi459 – 4591Divalent metal cation 1By similarity
Metal bindingi460 – 4601Divalent metal cation 1By similarity
Metal bindingi460 – 4601Divalent metal cation 2By similarity
Binding sitei460 – 4601cAMPBy similarity
Metal bindingi577 – 5771Divalent metal cation 1By similarity
Binding sitei577 – 5771cAMPBy similarity
Sitei580 – 5801Binds AMP, but not cAMPBy similarity
Binding sitei628 – 6281cAMPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi419 – 4235cAMPBy similarity

GO - Molecular functioni

  1. 3',5'-cyclic-AMP phosphodiesterase activity Source: RGD
  2. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. cAMP catabolic process Source: UniProtKB
  2. response to drug Source: RGD
  3. signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, Metal-binding

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
Alternative name(s):
DPDE2
Gene namesi
Name:Pde4a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3279. Pde4a.

Subcellular locationi

Cytoplasmperinuclear region By similarity

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. cytosol Source: RGD
  3. nucleus Source: RGD
  4. perinuclear region of cytoplasm Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi147 – 1471S → A: Abolishes phosphorylation by MAPKAPK2. 1 Publication
Mutagenesisi161 – 1611S → A: Does not affect phosphorylation by MAPKAPK2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4APRO_0000198808Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei147 – 1471Phosphoserine; by MAPKAPK21 Publication
Modified residuei160 – 1601PhosphoserineBy similarity
Cross-linki344 – 344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Proteolytically cleaved by caspase-3.By similarity
Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP54748.
PRIDEiP54748.

PTM databases

PhosphoSiteiP54748.

Miscellaneous databases

PMAP-CutDBP54748.

Expressioni

Tissue specificityi

Isoform 2 is testis specific.

Gene expression databases

GenevestigatoriP54748.

Interactioni

Subunit structurei

Interacts with LYN and ARRB2.By similarity

Structurei

Secondary structure

1
844
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 97Combined sources
Helixi16 – 194Combined sources
Helixi20 – 234Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortaliP54748.
SMRiP54748. Positions 337-698.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54748.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni317 – 710394CatalyticBy similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG122287.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP54748.
KOiK13293.
PhylomeDBiP54748.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P54748-1) [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 IRIQQRGYPD
60 70 80 90 100
SAERSETERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS
110 120 130 140 150
RRLEAENGPT PSPGRSPLDS QASPGLVLHA GATTSQRRES FLYRSDSDYD
160 170 180 190 200
MSPKAVSRSS SVASEAHAED LIVTPFAQVL ASLRSVRSNF SLLTNVPIPS
210 220 230 240 250
NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS
260 270 280 290 300
EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP
310 320 330 340 350
RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL
360 370 380 390 400
LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT
410 420 430 440 450
MMMYMLTLED 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 QSPSPPLEEE PGGLGHPSLP DKFQFELTLE
710 720 730 740 750
EEEEEDSLEV PGLPTTEETF LAAEDARAQA VDWSKVKGPS TTVVEVAERL
760 770 780 790 800
KQETASAYGA PQESMEAVGC SFSPGTPILP DVRTLSSSEE APGLLGLPST
810 820 830 840
AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG GDPA
Length:844
Mass (Da):93,439
Last modified:October 1, 1996 - v1
Checksum:i1A5F5101E4DBF1B6
GO
Isoform 2 (identifier: P54748-2) [UniParc]FASTAAdd to Basket

Also known as: PDE4A8

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

Show »
Length:763
Mass (Da):84,647
Checksum:i9E1E33481260566A
GO
Isoform 3 (identifier: P54748-3) [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):68,161
Checksum:iFE439ACE95E1D1AC
GO
Isoform 4 (identifier: P54748-4) [UniParc]FASTAAdd to Basket

Also known as: Medium

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: Missing.

Show »
Length:585
Mass (Da):65,059
Checksum:i3A188A286A28E174
GO
Isoform 5 (identifier: P54748-5) [UniParc]FASTAAdd to Basket

Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-318: Missing.
     354-386: Missing.

Show »
Length:493
Mass (Da):54,526
Checksum:i53735B34F1122F97
GO
Isoform 6 (identifier: P54748-6) [UniParc]FASTAAdd to Basket

Also known as: PDE4A10

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

Note: Incomplete sequence.

Show »
Length:771
Mass (Da):85,344
Checksum:iC1DB345199B5D59C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti130 – 1301A → R in AAF14352. (PubMed:11306681)Curated
Sequence conflicti465 – 4662GV → AL in AAA41848. (PubMed:2546153)Curated
Sequence conflicti465 – 4662GV → AL in AAA41823. (PubMed:2546153)Curated
Sequence conflicti603 – 6042GD → AH in AAA41848. (PubMed:2546153)Curated
Sequence conflicti603 – 6042GD → AH in AAA41823. (PubMed:2546153)Curated
Sequence conflicti833 – 8331A → T in AAC37699. (PubMed:2542942)Curated
Sequence conflicti833 – 8331A → T in AAA41101. (PubMed:2542942)Curated
Sequence conflicti833 – 8331A → T in AAA41102. (PubMed:2542942)Curated
Sequence conflicti833 – 8331A → T in AAF14352. (PubMed:11306681)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 318318Missing in isoform 5. 2 PublicationsVSP_004569Add
BLAST
Alternative sequencei1 – 259259Missing in isoform 4. 2 PublicationsVSP_004568Add
BLAST
Alternative sequencei1 – 234234Missing in isoform 3. 2 PublicationsVSP_004566Add
BLAST
Alternative sequencei1 – 102102MEPPA…GSSRR → MPSRKRLTLPRIFIVRKNGN S in isoform 2. 1 PublicationVSP_004565Add
BLAST
Alternative sequencei1 – 102102MEPPA…GSSRR → ALPLGPESLTHFSFSEEDTL RHPPGRCVS in isoform 6. CuratedVSP_038187Add
BLAST
Alternative sequencei235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 3. 2 PublicationsVSP_004567Add
BLAST
Alternative sequencei354 – 38633Missing in isoform 5. 2 PublicationsVSP_004570Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI53865.
I67946.
RefSeqiNP_037233.3. NM_013101.3. [P54748-1]
UniGeneiRn.91357.

Genome annotation databases

GeneIDi25638.
KEGGirno:25638.
UCSCiRGD:3279. rat. [P54748-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI53865.
I67946.
RefSeqiNP_037233.3. NM_013101.3. [P54748-1]
UniGeneiRn.91357.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortaliP54748.
SMRiP54748. Positions 337-698.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

ChEMBLiCHEMBL2094267.

PTM databases

PhosphoSiteiP54748.

Proteomic databases

PaxDbiP54748.
PRIDEiP54748.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25638.
KEGGirno:25638.
UCSCiRGD:3279. rat. [P54748-1]

Organism-specific databases

CTDi5141.
RGDi3279. Pde4a.

Phylogenomic databases

eggNOGiNOG122287.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP54748.
KOiK13293.
PhylomeDBiP54748.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.

Miscellaneous databases

EvolutionaryTraceiP54748.
NextBioi607467.
PMAP-CutDBP54748.

Gene expression databases

GenevestigatoriP54748.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiPDE4A_RAT
AccessioniPrimary (citable) accession number: P54748
Secondary accession number(s): P14645, Q9EQR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: January 7, 2015
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.