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P54748

- PDE4A_RAT

UniProt

P54748 - PDE4A_RAT

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Protein
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Gene
Pde4a
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

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-3 By similarity
Active sitei419 – 4191Proton donor By similarity
Metal bindingi423 – 4231Divalent metal cation 1 By similarity
Metal bindingi459 – 4591Divalent metal cation 1 By similarity
Metal bindingi460 – 4601Divalent metal cation 1 By similarity
Metal bindingi460 – 4601Divalent metal cation 2 By similarity
Binding sitei460 – 4601cAMP By similarity
Metal bindingi577 – 5771Divalent metal cation 1 By similarity
Binding sitei577 – 5771cAMP By similarity
Sitei580 – 5801Binds AMP, but not cAMP By similarity
Binding sitei628 – 6281cAMP By similarity

Regions

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

GO - Molecular functioni

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

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 4A
PRO_0000198808Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei147 – 1471Phosphoserine; by MAPKAPK21 Publication
Modified residuei160 – 1601Phosphoserine By 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.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP54748.
PRIDEiP54748.

PTM databases

PhosphoSiteiP54748.

Miscellaneous databases

PMAP-CutDBiP54748.

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

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortaliP54748.
SMRiP54748. Positions 337-698.

Miscellaneous databases

EvolutionaryTraceiP54748.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni317 – 710394Catalytic By similarity
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG122287.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP54748.
KOiK01120.
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

MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYPD    50
SAERSETERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS 100
RRLEAENGPT PSPGRSPLDS QASPGLVLHA GATTSQRRES FLYRSDSDYD 150
MSPKAVSRSS SVASEAHAED LIVTPFAQVL ASLRSVRSNF SLLTNVPIPS 200
NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS 250
EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP 300
RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL 350
LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT 400
MMMYMLTLED HYHADVAYHN SLHAADVLQS THVLLATPAL DAVFTDLEIL 450
AALFAAAIHD VDHPGVSNQF LINTNSELAL MYNDESVLEN HHLAVGFKLL 500
QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA DLKTMVETKK 550
VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF 600
QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD 650
AQDILDTLED NRDWYHSAIR QSPSPPLEEE PGGLGHPSLP DKFQFELTLE 700
EEEEEDSLEV PGLPTTEETF LAAEDARAQA VDWSKVKGPS TTVVEVAERL 750
KQETASAYGA PQESMEAVGC SFSPGTPILP DVRTLSSSEE APGLLGLPST 800
AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG GDPA 844
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 318318Missing in isoform 5.
VSP_004569Add
BLAST
Alternative sequencei1 – 259259Missing in isoform 4.
VSP_004568Add
BLAST
Alternative sequencei1 – 234234Missing in isoform 3.
VSP_004566Add
BLAST
Alternative sequencei1 – 102102MEPPA…GSSRR → MPSRKRLTLPRIFIVRKNGN S in isoform 2.
VSP_004565Add
BLAST
Alternative sequencei1 – 102102MEPPA…GSSRR → ALPLGPESLTHFSFSEEDTL RHPPGRCVS in isoform 6.
VSP_038187Add
BLAST
Alternative sequencei235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 3.
VSP_004567Add
BLAST
Alternative sequencei354 – 38633Missing in isoform 5.
VSP_004570Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti130 – 1301A → R in AAF14352. 1 Publication
Sequence conflicti465 – 4662GV → AL in AAA41848. 1 Publication
Sequence conflicti465 – 4662GV → AL in AAA41823. 1 Publication
Sequence conflicti603 – 6042GD → AH in AAA41848. 1 Publication
Sequence conflicti603 – 6042GD → AH in AAA41823. 1 Publication
Sequence conflicti833 – 8331A → T in AAC37699. 1 Publication
Sequence conflicti833 – 8331A → T in AAA41101. 1 Publication
Sequence conflicti833 – 8331A → T in AAA41102. 1 Publication
Sequence conflicti833 – 8331A → T in AAF14352. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
PIRi I53865.
I67946.
RefSeqi NP_037233.3. NM_013101.3. [P54748-1 ]
UniGenei Rn.91357.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LOI NMR - A 1-25 [» ]
ProteinModelPortali P54748.
SMRi P54748. Positions 337-698.
ModBasei Search...

Chemistry

BindingDBi P54748.
ChEMBLi CHEMBL2094267.

PTM databases

PhosphoSitei P54748.

Proteomic databases

PaxDbi P54748.
PRIDEi P54748.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25638.
KEGGi rno:25638.
UCSCi RGD:3279. rat. [P54748-1 ]

Organism-specific databases

CTDi 5141.
RGDi 3279. Pde4a.

Phylogenomic databases

eggNOGi NOG122287.
HOGENOMi HOG000236297.
HOVERGENi HBG108239.
InParanoidi P54748.
KOi K01120.
PhylomeDBi P54748.

Enzyme and pathway databases

UniPathwayi UPA00762 ; UER00747 .

Miscellaneous databases

EvolutionaryTracei P54748.
NextBioi 607467.
PMAP-CutDBi P54748.

Gene expression databases

Genevestigatori P54748.

Family and domain databases

Gene3Di 1.10.1300.10. 1 hit.
InterProi IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view ]
Pfami PF00233. PDEase_I. 1 hit.
[Graphical view ]
PRINTSi PR00387. PDIESTERASE1.
SMARTi SM00471. HDc. 1 hit.
[Graphical view ]
PROSITEi PS00126. PDEASE_I. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 113 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

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