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Q01063 (PDE4D_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

EC=3.1.4.53
Alternative name(s):
DPDE3
Gene names
Name:Pde4d
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length747 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. Activated by phosphatidic acid By similarity.

Pathway

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

Subunit structure

Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Binds ARRB2. Interacts with PDE4DIP By similarity. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Interacts (via N-terminus region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner. Ref.6 Ref.7

Subcellular location

Cytoplasm. Membrane. Cytoplasmcytoskeleton. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Apical cell membrane By similarity. Note: Colocalized with SHANK2 to the apical membrane of colonic crypt cells By similarity. Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome.

Tissue specificity

Expressed in brain (at protein level). Isoform 7 is detected in heart, brain, lung, kidney and testis. Ref.1 Ref.6

Induction

Up-regulated by cAMP and follicle-stimulating hormone By similarity.

Post-translational modification

Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation By similarity.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityAlternative splicing
   LigandcAMP
Metal-binding
   Molecular functionHydrolase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from mutant phenotype PubMed 10518565. Source: MGI

cAMP catabolic process

Inferred from direct assay PubMed 21670503. Source: BHF-UCL

cellular response to cAMP

Inferred from electronic annotation. Source: Ensembl

cellular response to epinephrine stimulus

Inferred from mutant phenotype PubMed 16213210. Source: BHF-UCL

cellular response to lipopolysaccharide

Inferred from mutant phenotype PubMed 15585880. Source: MGI

establishment of endothelial barrier

Inferred from sequence or structural similarity. Source: UniProtKB

leukocyte migration

Inferred from mutant phenotype PubMed 15585880. Source: MGI

multicellular organism growth

Inferred from mutant phenotype PubMed 10518565. Source: MGI

negative regulation of heart contraction

Inferred from mutant phenotype PubMed 21903937. Source: BHF-UCL

negative regulation of peptidyl-serine phosphorylation

Inferred from mutant phenotype PubMed 16213210. Source: BHF-UCL

negative regulation of relaxation of cardiac muscle

Inferred from mutant phenotype PubMed 21670503. Source: BHF-UCL

neutrophil chemotaxis

Inferred from mutant phenotype PubMed 15585880. Source: MGI

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-2 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-5 production

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle cell contraction

Inferred from mutant phenotype PubMed 21670503PubMed 21903937. Source: BHF-UCL

regulation of cell communication by electrical coupling involved in cardiac conduction

Inferred by curator PubMed 16213210. Source: BHF-UCL

regulation of heart rate

Inferred from mutant phenotype PubMed 16213210. Source: BHF-UCL

regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

Inferred from mutant phenotype PubMed 16213210. Source: BHF-UCL

regulation of ryanodine-sensitive calcium-release channel activity

Inferred from mutant phenotype PubMed 16213210. Source: BHF-UCL

smooth muscle contraction

Inferred from mutant phenotype PubMed 14519662. Source: MGI

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

calcium channel complex

Inferred from direct assay PubMed 16213210. Source: BHF-UCL

cytosol

Inferred from electronic annotation. Source: Ensembl

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_function3',5'-cyclic-AMP phosphodiesterase activity

Inferred from electronic annotation. Source: Ensembl

3',5'-cyclic-nucleotide phosphodiesterase activity

Inferred from direct assay PubMed 21670503. Source: BHF-UCL

ATPase binding

Inferred from physical interaction PubMed 21903937. Source: BHF-UCL

cAMP binding

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

ion channel binding

Inferred from physical interaction PubMed 16213210PubMed 21670503. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Adrb1P349713EBI-7764239,EBI-7764182

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 7 (identifier: Q01063-1)

Also known as: PDE4D7;

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 9 (identifier: Q01063-2)

Also known as: PDE4D9;

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.
     70-91: RPTSLPLKILPLIAVTSADSSG → MSIIMKPRSRSTSSLRTTEAVC
Isoform 3 (identifier: Q01063-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: Missing.
     164-208: PFAQVLASLR...QPSINKATIT → MKEQPSCAGT...TESSFPCLFA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 747747cAMP-specific 3',5'-cyclic phosphodiesterase 4D
PRO_0000198815

Regions

Nucleotide binding401 – 4055cAMP By similarity

Sites

Active site4011Proton donor By similarity
Metal binding4051Divalent metal cation 1 By similarity
Metal binding4411Divalent metal cation 1 By similarity
Metal binding4421Divalent metal cation 1 By similarity
Metal binding4421Divalent metal cation 2 By similarity
Metal binding5591Divalent metal cation 1 By similarity
Binding site4421cAMP By similarity
Site5621Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue2381Phosphoserine By similarity
Modified residue2401Phosphoserine By similarity
Cross-link326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 163163Missing in isoform 3.
VSP_012394
Alternative sequence1 – 6969Missing in isoform 9.
VSP_012395
Alternative sequence70 – 9122RPTSL…ADSSG → MSIIMKPRSRSTSSLRTTEA VC in isoform 9.
VSP_012396
Alternative sequence164 – 20845PFAQV…KATIT → MKEQPSCAGTGHPSMAGYGR MAPFELAGGPVKRLRTESSF PCLFA in isoform 3.
VSP_012397

Experimental info

Sequence conflict403 – 4042NI → SR in AAA37368. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 7 (PDE4D7) [UniParc].

Last modified January 4, 2005. Version 2.
Checksum: 68402163664B3676

FASTA74784,563
        10         20         30         40         50         60 
MERDTCDVLS RSKSASEETL HSCNEEEDPF RGMEPYLVRR LSSRSIQLPP LAFRQLEQAD 

        70         80         90        100        110        120 
LRSESENIPR PTSLPLKILP LIAVTSADSS GFDVDNGTSA GRSPLDPMTS PGSGLILQAN 

       130        140        150        160        170        180 
FVHSQRRESF LYRSDSDYDL SPKSMSRNSS IASDIHGDDL IVTPFAQVLA SLRTVRNNFA 

       190        200        210        220        230        240 
ALTNLQDRAP SKRSPMCNQP SINKATITEE AYQKLASETL EELDWCLDQL ETLQTRHSVS 

       250        260        270        280        290        300 
EMASNKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTQ KEKEKKKRPM 

       310        320        330        340        350        360 
SQISGVKKLM HSSSLTNSCI PRFGVKTEQE DVLAKELEDV NKWGLHVFRI AELSGNRPLT 

       370        380        390        400        410        420 
VIMHTIFQER DLLKTFKIPV DTLITYLMTL EDHYHADVAY HNNIHAADVV QSTHVLLSTP 

       430        440        450        460        470        480 
ALEAVFTDLE ILAAIFASAI HDVDHPGVSN QFLINTNSEL ALMYNDSSVL ENHHLAVGFK 

       490        500        510        520        530        540 
LLQEENCDIF QNLTKKQRQS LRKMVIDIVL ATDMSKHMNL LADLKTMVET KKVTSSGVLL 

       550        560        570        580        590        600 
LDNYSDRIQV LQNMVHCADL SNPTKPLQLY RQWTDRIMEE FFRQGDRERE RGMEISPMCD 

       610        620        630        640        650        660 
KHNASVEKSQ VGFIDYIVHP LWETWADLVH PDAQDILDTL EDNREWYQST IPQSPSPAPD 

       670        680        690        700        710        720 
DQEEGRQGQT EKFQFELTLE EDCESDTEKD SGSQVEEDTS CSDSKTLCTQ DSESTEIPLD 

       730        740 
EQVEEEAVAE EESQPETCVP DDCCPDT 

« Hide

Isoform 9 (PDE4D9) [UniParc].

Checksum: 51D44F3467C9B71A
Show »

FASTA67876,817
Isoform 3 [UniParc].

Checksum: CEDFA3A57387798E
Show »

FASTA58466,394

References

« Hide 'large scale' references
[1]"Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7."
Wang D., Deng C., Bugaj-Gaweda B., Kwan M., Gunwaldsen C., Leonard C., Xin X., Hu Y., Unterbeck A., De Vivo M.
Cell. Signal. 15:883-891(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), TISSUE SPECIFICITY.
Strain: BALB/c.
[2]Chai H., Gaweda B., De Vivo M., Wang D.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9).
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: C57BL/6J.
Tissue: Head.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase."
Repaske D.R., Swinnen J.V., Jin S.-L.C., van Wyk J.J., Conti M.
J. Biol. Chem. 267:18683-18688(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 400-514.
[6]"Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors."
Lee J.H., Richter W., Namkung W., Kim K.H., Kim E., Conti M., Lee M.G.
J. Biol. Chem. 282:10414-10422(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHANK2, TISSUE SPECIFICITY.
[7]"Remodeling of ryanodine receptor complex causes 'leaky' channels: a molecular mechanism for decreased exercise capacity."
Bellinger A.M., Reiken S., Dura M., Murphy P.W., Deng S.X., Landry D.W., Nieman D., Lehnart S.E., Samaru M., LaCampagne A., Marks A.R.
Proc. Natl. Acad. Sci. U.S.A. 105:2198-2202(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH RYR1; FKBP1A; PKA AND PP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF536978 mRNA. Translation: AAN10120.1.
AY388962 mRNA. Translation: AAQ90406.1.
AK081466 mRNA. Translation: BAC38226.1.
CT025605, AC161585, AC163650 Genomic DNA. Translation: CAQ51656.1.
M94541 mRNA. Translation: AAA37368.1. Different termination.
RefSeqNP_035186.1. NM_011056.3.
XP_006517710.1. XM_006517647.1.
UniGeneMm.434429.

3D structure databases

ProteinModelPortalQ01063.
SMRQ01063. Positions 244-678.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid232023. 3 interactions.
DIPDIP-29706N.
IntActQ01063. 2 interactions.

Chemistry

BindingDBQ01063.
ChEMBLCHEMBL2111373.
DrugBankDB00131. Adenosine monophosphate.

PTM databases

PhosphoSiteQ01063.

Proteomic databases

PaxDbQ01063.
PRIDEQ01063.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000074103; ENSMUSP00000073742; ENSMUSG00000021699. [Q01063-2]
ENSMUST00000120664; ENSMUSP00000113024; ENSMUSG00000021699. [Q01063-3]
ENSMUST00000122041; ENSMUSP00000113488; ENSMUSG00000021699. [Q01063-1]
ENSMUST00000177907; ENSMUSP00000136485; ENSMUSG00000021699. [Q01063-1]
GeneID238871.
KEGGmmu:238871.
UCSCuc007rvg.2. mouse. [Q01063-1]
uc007rvj.2. mouse. [Q01063-2]

Organism-specific databases

CTD5144.
MGIMGI:99555. Pde4d.

Phylogenomic databases

eggNOGNOG122287.
GeneTreeENSGT00740000115148.
HOGENOMHOG000236297.
HOVERGENHBG108239.
KOK01120.
OMAQHEVEMP.
OrthoDBEOG7HQNBC.
PhylomeDBQ01063.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressQ01063.
BgeeQ01063.
CleanExMM_PDE4D.
GenevestigatorQ01063.

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

NextBio383911.
PROQ01063.
SOURCESearch...

Entry information

Entry namePDE4D_MOUSE
AccessionPrimary (citable) accession number: Q01063
Secondary accession number(s): B2KF58 expand/collapse secondary AC list , Q6TRH9, Q8C4Q7, Q8CG05
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 4, 2005
Last modified: April 16, 2014
This is version 127 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