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O89084

- PDE4A_MOUSE

UniProt

O89084 - PDE4A_MOUSE

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Protein

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

Gene
Pde4a
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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 and diazepam.1 Publication

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: MGI
  2. 3',5'-cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
  3. cAMP binding Source: Ensembl
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. cAMP catabolic process Source: BHF-UCL
  2. cellular response to drug Source: MGI
  3. regulation of cAMP-mediated signaling Source: MGI
  4. regulation of protein kinase A signaling Source: MGI
  5. sensory perception of smell Source: MGI
  6. signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_203795. DARPP-32 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:99558. Pde4a.

Subcellular locationi

Cytoplasmperinuclear region By similarity

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 844844cAMP-specific 3',5'-cyclic phosphodiesterase 4APRO_0000198807Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei147 – 1471Phosphoserine; by MAPKAPK2 By similarity
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 By similarity.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO89084.
PaxDbiO89084.
PRIDEiO89084.

PTM databases

PhosphoSiteiO89084.

Expressioni

Gene expression databases

ArrayExpressiO89084.
BgeeiO89084.
CleanExiMM_PDE4A.
GenevestigatoriO89084.

Interactioni

Subunit structurei

Interacts with LYN and ARRB2 By similarity.

Protein-protein interaction databases

MINTiMINT-4996302.

Structurei

3D structure databases

ProteinModelPortaliO89084.
SMRiO89084. Positions 254-696.

Family & Domainsi

Region

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG122287.
GeneTreeiENSGT00740000115148.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiO89084.
KOiK01120.
OMAiPSPTMKD.
OrthoDBiEOG7HQNBC.
PhylomeDBiO89084.
TreeFamiTF314638.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

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

MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD    50
SAERSEPERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS 100
RRLEAENGPT PSPGRSPLDS QASPGLMLHA GAATSQRRES FLYRSDSDYD 150
MSPKTMSRNS SVASEAHGED LIVTPFAQVL ASLRNVRSNF SLLTNVPIPS 200
NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS 250
EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTP 300
RQRPFQQPPP AAVQQAQPMS QITGLKKLVH TGSLNINVPR FGVKTDQEDL 350
LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT 400
MMTYMLTLED 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 QSPSPTLEEE PGVLSDPALP DKFQFELTLE 700
EEDEEDSLEV PGLPCTEETL LAPHDTRAQA MEQSKVKGQS PAVVEVAESL 750
KQETASAHGA PEESAEAVGH SFSLETSILP DLRTLSPSEE AQGLLGLPSM 800
AAEVEAPRDH LAAMRACSAC SGTSGDNSAV ISAPGRWGSG GDPA 844
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 AAH27224.2 differs from that shown. Reason: Erroneous initiation.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 234234Missing in isoform 2. VSP_004563Add
BLAST
Alternative sequencei1 – 102102MEPPA…GSSRR → MRSSAAPRARPRPPALALPL GPESLTHFSFSEEDTLRHPP GRCVS in isoform 3. VSP_004562Add
BLAST
Alternative sequencei235 – 25622WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 2. VSP_004564Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti516 – 5161R → K in AAF19201. 1 Publication
Sequence conflicti685 – 6851S → G in AAH27224. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
RefSeqiNP_062772.3. NM_019798.5. [O89084-2]
NP_899668.1. NM_183408.3. [O89084-1]
XP_006510155.1. XM_006510092.1. [O89084-3]
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS22895.1. [O89084-1 ]
CCDS22896.1. [O89084-2 ]
RefSeqi NP_062772.3. NM_019798.5. [O89084-2 ]
NP_899668.1. NM_183408.3. [O89084-1 ]
XP_006510155.1. XM_006510092.1. [O89084-3 ]
UniGenei Mm.191749.

3D structure databases

ProteinModelPortali O89084.
SMRi O89084. Positions 254-696.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

MINTi MINT-4996302.

Chemistry

BindingDBi O89084.
ChEMBLi CHEMBL2111373.

PTM databases

PhosphoSitei O89084.

Proteomic databases

MaxQBi O89084.
PaxDbi O89084.
PRIDEi O89084.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000003395 ; ENSMUSP00000003395 ; ENSMUSG00000032177 . [O89084-2 ]
ENSMUST00000039413 ; ENSMUSP00000037025 ; ENSMUSG00000032177 . [O89084-1 ]
ENSMUST00000115458 ; ENSMUSP00000111118 ; ENSMUSG00000032177 . [O89084-3 ]
GeneIDi 18577.
KEGGi mmu:18577.
UCSCi uc009oki.2. mouse. [O89084-1 ]
uc009okl.2. mouse. [O89084-3 ]
uc009okm.2. mouse. [O89084-2 ]

Organism-specific databases

CTDi 5141.
MGIi MGI:99558. Pde4a.

Phylogenomic databases

eggNOGi NOG122287.
GeneTreei ENSGT00740000115148.
HOGENOMi HOG000236297.
HOVERGENi HBG108239.
InParanoidi O89084.
KOi K01120.
OMAi PSPTMKD.
OrthoDBi EOG7HQNBC.
PhylomeDBi O89084.
TreeFami TF314638.

Enzyme and pathway databases

UniPathwayi UPA00762 ; UER00747 .
Reactomei REACT_203795. DARPP-32 events.

Miscellaneous databases

NextBioi 294438.
PROi O89084.
SOURCEi Search...

Gene expression databases

ArrayExpressi O89084.
Bgeei O89084.
CleanExi MM_PDE4A.
Genevestigatori O89084.

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

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiPDE4A_MOUSE
AccessioniPrimary (citable) accession number: O89084
Secondary accession number(s): Q8R078
, Q9JHQ4, Q9QX48, Q9QX49, Q9QXI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: March 1, 2002
Last modified: September 3, 2014
This is version 113 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

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