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P14646

- PDE4B_RAT

UniProt

P14646 - PDE4B_RAT

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Protein

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

Gene
Pde4b
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

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

Kineticsi

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

  1. KM=5.4 µM for cAMP (isoform 4)1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei406 – 4061Proton donor By similarity
Metal bindingi410 – 4101Divalent metal cation 1 By similarity
Metal bindingi446 – 4461Divalent metal cation 1 By similarity
Metal bindingi447 – 4471Divalent metal cation 1 By similarity
Metal bindingi447 – 4471Divalent metal cation 2 By similarity
Binding sitei447 – 4471cAMP By similarity
Metal bindingi564 – 5641Divalent metal cation 1 By similarity
Binding sitei564 – 5641cAMP By similarity
Sitei567 – 5671Binds AMP, but not cAMP By similarity
Binding sitei615 – 6151cAMP By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi406 – 4105cAMP By similarity

GO - Molecular functioni

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

GO - Biological processi

  1. cAMP catabolic process Source: UniProtKB
  2. cellular response to drug Source: Ensembl
  3. cellular response to lipopolysaccharide Source: Ensembl
  4. neutrophil chemotaxis Source: Ensembl
  5. neutrophil homeostasis Source: Ensembl
  6. positive regulation of interferon-gamma production Source: Ensembl
  7. positive regulation of interleukin-2 production Source: Ensembl
  8. T cell receptor signaling pathway Source: Ensembl
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 4B (EC:3.1.4.53)
Alternative name(s):
DPDE4
Gene namesi
Name:Pde4b
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 5

Organism-specific databases

RGDi3280. Pde4b.

Subcellular locationi

GO - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 736736cAMP-specific 3',5'-cyclic phosphodiesterase 4BPRO_0000198810Add
BLAST

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP14646.
PRIDEiP14646.

PTM databases

PhosphoSiteiP14646.

Expressioni

Tissue specificityi

Widely expressed. Isoform 3 expressed in brain, heart, lung and liver. Isoform 4 expressed in liver and brain.2 Publications

Inductioni

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.2 Publications

Gene expression databases

ArrayExpressiP14646.
GenevestigatoriP14646.

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP14646.
SMRiP14646. Positions 324-685.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG122287.
GeneTreeiENSGT00740000115148.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP14646.
KOiK01120.
OrthoDBiEOG7HQNBC.
PhylomeDBiP14646.
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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P14646-3) [UniParc]FASTAAdd to Basket

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.

« Hide

MKKSRSVMAV TADDNLKDYF ECSLSKSYSS SSYTLGIDLW RGRRCCSGNL    50
QLPPLSQRQS ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG 100
PSPGRSPLDP QASSSSGLVL HAAFPGHSQR RESFLYRSDS DYDLSPKAMS 150
RNSSLPSEQH GDDLIVTPFA QVLASLRIVR NNFTLLTNLH GAPNKRSPAA 200
SQAPVTRVSL QEESYQKLAM ETLEELDWCL DQLETIQTYR SVSEMASNKF 250
KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK 300
KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL 350
NIFNVAGYSH NRPLTCIMYA IFQERDLLKT FKISSDTFVT YMMTLEDHYH 400
SDVAYHNSLH AADVAQSTHV LLSTPALDAV FTDLEILAAI FAAAIHDVDH 450
PGVSNQFLIN TNSELALMYN DESVLENHHL AVGFKLLQEE HCDIFQNLTK 500
KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS SGVLLLDNYT 550
DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI 600
SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN 650
WYQSMIPQSP SPPLDERSRD CQGLMEKFQF ELTLEEEDSE GPEKEGEGPN 700
YFSSTKTLCV IDPENRDSLE ETDIDIATED KSLIDT 736
Length:736
Mass (Da):83,375
Last modified:July 10, 2007 - v4
Checksum:iC48F576EFA8DF498
GO
Isoform 2 (identifier: P14646-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:564
Mass (Da):64,265
Checksum:iEDF8D50D4C5A701C
GO
Isoform 3 (identifier: P14646-1) [UniParc]FASTAAdd to Basket

Also known as: PDE4B3

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMAV...SIAITTVSQE → MTAKNSSKEL...QRRRFTVAHT

Show »
Length:721
Mass (Da):82,101
Checksum:iC6FB885E6107BD4D
GO
Isoform 4 (identifier: P14646-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:659
Mass (Da):75,085
Checksum:i730AC799838E0D73
GO
Isoform 5 (identifier: P14646-5) [UniParc]FASTAAdd to Basket

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.

Show »
Length:722
Mass (Da):81,737
Checksum:i2C74F02173E5ED17
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 172172Missing in isoform 2. VSP_026678Add
BLAST
Alternative sequencei1 – 9393MKKSR…TVSQE → MTAKNSSKELPASESEVCIK TFKEQMRLELELPKLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform 3 and isoform 5. VSP_026679Add
BLAST
Alternative sequencei1 – 9393MKKSR…TVSQE → MLHVNDLPPPRRHSWI in isoform 4. VSP_026680Add
BLAST
Alternative sequencei173 – 21139LASLR…RVSLQ → MKEQGGTVSGAGSSRGGGDS AMASLQPLQPNYLSVCLFA in isoform 2. VSP_004573Add
BLAST
Alternative sequencei710 – 73627VIDPE…SLIDT → KPCHAANGLALPVGGGNAAS TQPRCGHV in isoform 5. VSP_026681Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti178 – 1781I → S in AAL31763. 1 Publication
Sequence conflicti178 – 1781I → S in AAL31764. 1 Publication
Sequence conflicti178 – 1781I → S in AAH85704. 1 Publication
Sequence conflicti531 – 5311T → S in AAA18926. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L27058 mRNA. Translation: AAA74478.1.
U01291
, 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.
PIRiA40949.
I59143.
RefSeqiNP_058727.2. NM_017031.2. [P14646-1]
UniGeneiRn.37733.

Genome annotation databases

EnsembliENSRNOT00000007738; ENSRNOP00000007738; ENSRNOG00000005905.
GeneIDi24626.
KEGGirno:24626.
UCSCiRGD:3280. rat. [P14646-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L27058 mRNA. Translation: AAA74478.1 .
U01291
, 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 .
PIRi A40949.
I59143.
RefSeqi NP_058727.2. NM_017031.2. [P14646-1 ]
UniGenei Rn.37733.

3D structure databases

ProteinModelPortali P14646.
SMRi P14646. Positions 324-685.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P14646.
ChEMBLi CHEMBL2094267.

PTM databases

PhosphoSitei P14646.

Proteomic databases

PaxDbi P14646.
PRIDEi P14646.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000007738 ; ENSRNOP00000007738 ; ENSRNOG00000005905 .
GeneIDi 24626.
KEGGi rno:24626.
UCSCi RGD:3280. rat. [P14646-3 ]

Organism-specific databases

CTDi 5142.
RGDi 3280. Pde4b.

Phylogenomic databases

eggNOGi NOG122287.
GeneTreei ENSGT00740000115148.
HOGENOMi HOG000236297.
HOVERGENi HBG108239.
InParanoidi P14646.
KOi K01120.
OrthoDBi EOG7HQNBC.
PhylomeDBi P14646.
TreeFami TF314638.

Enzyme and pathway databases

UniPathwayi UPA00762 ; UER00747 .

Miscellaneous databases

NextBioi 603894.

Gene expression databases

ArrayExpressi P14646.
Genevestigatori P14646.

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. "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. Cited for: TISSUE SPECIFICITY, INDUCTION.

Entry informationi

Entry nameiPDE4B_RAT
AccessioniPrimary (citable) accession number: P14646
Secondary accession number(s): Q5RKL0, Q8VD81, Q8VD82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: July 10, 2007
Last modified: May 14, 2014
This is version 114 of the entry and version 4 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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