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P14646 (PDE4B_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 4B

EC=3.1.4.53
Alternative name(s):
DPDE4
Gene names
Name:Pde4b
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length736 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

Expression is under the control of follicle-stimulating hormone and cAMP. Inhibited by rolipram.

Pathway

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

Tissue specificity

Widely expressed. Isoform 3 expressed in brain, heart, lung and liver. Isoform 4 expressed in liver and brain. Ref.5 Ref.9

Induction

In Sertoli cells, induced by FSH. In the pineal gland, exhibits night/day variations with a 7-fold increased expression at night. Up-regulation is due to a large degree to the release of norepinephrine from nerve terminals in the pineal gland and cAMP signaling pathway. Ref.1 Ref.9

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Biophysicochemical properties

Kinetic parameters:

Vmax values for isoforms 2, 3 and 4 relative to isoform 1 are 3.8, 1.6 and 2.1.

KM=5.4 µM for cAMP (isoform 4) Ref.5

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandcAMP
Metal-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

cAMP catabolic process

Inferred from direct assay PubMed 21724846. Source: UniProtKB

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

neutrophil chemotaxis

Inferred from electronic annotation. Source: Ensembl

neutrophil homeostasis

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-2 production

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell periphery

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 15242814. Source: RGD

cytosol

Inferred from direct assay Ref.5. Source: RGD

nucleus

Inferred from direct assay PubMed 15242814. Source: RGD

perinuclear region of cytoplasm

Inferred from direct assay PubMed 15242814. Source: RGD

   Molecular_function3',5'-cyclic-AMP phosphodiesterase activity

Inferred from direct assay Ref.5PubMed 15242814. Source: RGD

cAMP binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P14646-3)

Also known as: PDE4B1;

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: P14646-2)

Also known as: PDE4B2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: Missing.
     173-211: LASLRIVRNN...QAPVTRVSLQ → MKEQGGTVSG...PNYLSVCLFA
Isoform 3 (identifier: P14646-1)

Also known as: PDE4B3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMAV...SIAITTVSQE → MTAKNSSKEL...QRRRFTVAHT
Isoform 4 (identifier: P14646-4)

Also known as: PDE4B4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMAV...SIAITTVSQE → MLHVNDLPPPRRHSWI
Note: Contains a phosphoserine at position 56. Activated by phosphorylation at Ser-56. Mutagenesis of Ser-56 abolishes activation.
Isoform 5 (identifier: P14646-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMAV...SIAITTVSQE → MTAKNSSKEL...QRRRFTVAHT
     710-736: VIDPENRDSLEETDIDIATEDKSLIDT → KPCHAANGLALPVGGGNAASTQPRCGHV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736cAMP-specific 3',5'-cyclic phosphodiesterase 4B
PRO_0000198810

Regions

Nucleotide binding406 – 4105cAMP By similarity

Sites

Active site4061Proton donor By similarity
Metal binding4101Divalent metal cation 1 By similarity
Metal binding4461Divalent metal cation 1 By similarity
Metal binding4471Divalent metal cation 1 By similarity
Metal binding4471Divalent metal cation 2 By similarity
Metal binding5641Divalent metal cation 1 By similarity
Binding site4471cAMP By similarity
Binding site5641cAMP By similarity
Binding site6151cAMP By similarity
Site5671Binds AMP, but not cAMP By similarity

Natural variations

Alternative sequence1 – 172172Missing in isoform 2.
VSP_026678
Alternative sequence1 – 9393MKKSR…TVSQE → MTAKNSSKELPASESEVCIK TFKEQMRLELELPKLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform 3 and isoform 5.
VSP_026679
Alternative sequence1 – 9393MKKSR…TVSQE → MLHVNDLPPPRRHSWI in isoform 4.
VSP_026680
Alternative sequence173 – 21139LASLR…RVSLQ → MKEQGGTVSGAGSSRGGGDS AMASLQPLQPNYLSVCLFA in isoform 2.
VSP_004573
Alternative sequence710 – 73627VIDPE…SLIDT → KPCHAANGLALPVGGGNAAS TQPRCGHV in isoform 5.
VSP_026681

Experimental info

Sequence conflict1781I → S in AAL31763. Ref.5
Sequence conflict1781I → S in AAL31764. Ref.5
Sequence conflict1781I → S in AAH85704. Ref.6
Sequence conflict5311T → S in AAA18926. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE4B1) [UniParc].

Last modified July 10, 2007. Version 4.
Checksum: C48F576EFA8DF498

FASTA73683,375
        10         20         30         40         50         60 
MKKSRSVMAV TADDNLKDYF ECSLSKSYSS SSYTLGIDLW RGRRCCSGNL QLPPLSQRQS 

        70         80         90        100        110        120 
ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG PSPGRSPLDP QASSSSGLVL 

       130        140        150        160        170        180 
HAAFPGHSQR RESFLYRSDS DYDLSPKAMS RNSSLPSEQH GDDLIVTPFA QVLASLRIVR 

       190        200        210        220        230        240 
NNFTLLTNLH GAPNKRSPAA SQAPVTRVSL QEESYQKLAM ETLEELDWCL DQLETIQTYR 

       250        260        270        280        290        300 
SVSEMASNKF KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK 

       310        320        330        340        350        360 
KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL NIFNVAGYSH 

       370        380        390        400        410        420 
NRPLTCIMYA IFQERDLLKT FKISSDTFVT YMMTLEDHYH SDVAYHNSLH AADVAQSTHV 

       430        440        450        460        470        480 
LLSTPALDAV FTDLEILAAI FAAAIHDVDH PGVSNQFLIN TNSELALMYN DESVLENHHL 

       490        500        510        520        530        540 
AVGFKLLQEE HCDIFQNLTK KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS 

       550        560        570        580        590        600 
SGVLLLDNYT DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI 

       610        620        630        640        650        660 
SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN WYQSMIPQSP 

       670        680        690        700        710        720 
SPPLDERSRD CQGLMEKFQF ELTLEEEDSE GPEKEGEGPN YFSSTKTLCV IDPENRDSLE 

       730 
ETDIDIATED KSLIDT 

« Hide

Isoform 2 (PDE4B2) [UniParc].

Checksum: EDF8D50D4C5A701C
Show »

FASTA56464,265
Isoform 3 (PDE4B3) [UniParc].

Checksum: C6FB885E6107BD4D
Show »

FASTA72182,101
Isoform 4 (PDE4B4) [UniParc].

Checksum: 730AC799838E0D73
Show »

FASTA65975,085
Isoform 5 [UniParc].

Checksum: 2C74F02173E5ED17
Show »

FASTA72281,737

References

« Hide 'large scale' references
[1]"Properties and hormonal regulation of two structurally related cAMP phosphodiesterases from the rat Sertoli cell."
Swinnen J.V., Tsikalas K.E., Conti M.
J. Biol. Chem. 266:18370-18377(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION.
Tissue: Sertoli cell.
[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] (ISOFORM 2).
[3]"Structure of two rat genes coding for closely related rolipram-sensitive cAMP phosphodiesterases. Multiple mRNA variants originate from alternative splicing and multiple start sites."
Monaco L., Vicini E., Conti M.
J. Biol. Chem. 269:347-357(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: Wistar.
[4]"Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3."
Huston E., Lumb S., Russell A., Catterall C., Ross A.H., Steele M.R., Bolger G.B., Perry M.J., Owens R.J., Houslay M.D.
Biochem. J. 328:549-558(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Olfactory bulb.
[5]"Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform."
Shepherd M., McSorley T., Olsen A.E., Johnston L.A., Thomson N.C., Baillie G.S., Houslay M.D., Bolger G.B.
Biochem. J. 370:429-438(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHORYLATION AT SER-56 (ISOFORM 4), TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Brain cortex.
[6]"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 5).
Tissue: Heart.
[7]"Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase."
Colicelli J., Birchmeier C., Michaeli T., O'Neill K., Riggs M., Wigler M.
Proc. Natl. Acad. Sci. U.S.A. 86:3599-3603(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 175-736.
Tissue: Brain.
[8]"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 304-663.
Tissue: Testis.
[9]"Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling."
Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q., Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F., Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C.
J. Biol. Chem. 284:7606-7622(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27058 mRNA. Translation: AAA74478.1.
U01291 expand/collapse EMBL AC list , U01289, U01293, U01294, U01295, U01296, U01297, U01298, U01290 Unassigned DNA. Translation: AAA18926.1.
U95748 mRNA. Translation: AAB96560.1.
AF202732 mRNA. Translation: AAL31763.1.
AF202733 mRNA. Translation: AAL31764.1.
BC085704 mRNA. Translation: AAH85704.1.
J04563 mRNA. Translation: AAA66039.1.
M25350 mRNA. Translation: AAA41846.1.
M28413 mRNA. Translation: AAA41824.1.
PIRA40949.
I59143.
RefSeqNP_058727.2. NM_017031.2.
UniGeneRn.37733.

3D structure databases

ProteinModelPortalP14646.
SMRP14646. Positions 324-685.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP14646.
ChEMBLCHEMBL2094267.

PTM databases

PhosphoSiteP14646.

Proteomic databases

PaxDbP14646.
PRIDEP14646.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000007738; ENSRNOP00000007738; ENSRNOG00000005905.
GeneID24626.
KEGGrno:24626.
UCSCRGD:3280. rat. [P14646-3]

Organism-specific databases

CTD5142.
RGD3280. Pde4b.

Phylogenomic databases

eggNOGNOG122287.
GeneTreeENSGT00740000115148.
HOGENOMHOG000236297.
HOVERGENHBG108239.
InParanoidP14646.
KOK01120.
OrthoDBEOG7HQNBC.
PhylomeDBP14646.
TreeFamTF314638.

Enzyme and pathway databases

UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressP14646.
GenevestigatorP14646.

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

NextBio603894.

Entry information

Entry namePDE4B_RAT
AccessionPrimary (citable) accession number: P14646
Secondary accession number(s): Q5RKL0, Q8VD81, Q8VD82
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: July 10, 2007
Last modified: April 16, 2014
This is version 113 of the entry and version 4 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