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Protein

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

Gene

Pde4b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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

a divalent metal cationBy similarityNote: 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 donorBy similarity
    Metal bindingi410 – 4101Divalent metal cation 1By similarity
    Metal bindingi446 – 4461Divalent metal cation 1By similarity
    Metal bindingi447 – 4471Divalent metal cation 1By similarity
    Metal bindingi447 – 4471Divalent metal cation 2By similarity
    Binding sitei447 – 4471cAMPBy similarity
    Metal bindingi564 – 5641Divalent metal cation 1By similarity
    Binding sitei564 – 5641cAMPBy similarity
    Sitei567 – 5671Binds AMP, but not cAMPBy similarity
    Binding sitei615 – 6151cAMPBy similarity

    Regions

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

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    BRENDAi3.1.4.53. 5301.
    ReactomeiREACT_287445. G alpha (s) signalling events.
    REACT_348359. DARPP-32 events.
    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 Componenti: Unplaced

    Organism-specific databases

    RGDi3280. Pde4b.

    Subcellular locationi

    GO - Cellular componenti

    • cell periphery Source: Ensembl
    • cytoplasm Source: RGD
    • cytosol Source: RGD
    • nucleus Source: RGD
    • 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

    ExpressionAtlasiP14646. baseline and differential.
    GenevestigatoriP14646.

    Interactioni

    Structurei

    3D structure databases

    ProteinModelPortaliP14646.
    SMRiP14646. Positions 324-685.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG122287.
    HOGENOMiHOG000236297.
    HOVERGENiHBG108239.
    InParanoidiP14646.
    KOiK13293.
    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. AlignAdd to basket

    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

            10         20         30         40         50
    MKKSRSVMAV TADDNLKDYF ECSLSKSYSS SSYTLGIDLW RGRRCCSGNL
    60 70 80 90 100
    QLPPLSQRQS ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG
    110 120 130 140 150
    PSPGRSPLDP QASSSSGLVL HAAFPGHSQR RESFLYRSDS DYDLSPKAMS
    160 170 180 190 200
    RNSSLPSEQH GDDLIVTPFA QVLASLRIVR NNFTLLTNLH GAPNKRSPAA
    210 220 230 240 250
    SQAPVTRVSL QEESYQKLAM ETLEELDWCL DQLETIQTYR SVSEMASNKF
    260 270 280 290 300
    KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK
    310 320 330 340 350
    KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL
    360 370 380 390 400
    NIFNVAGYSH NRPLTCIMYA IFQERDLLKT FKISSDTFVT YMMTLEDHYH
    410 420 430 440 450
    SDVAYHNSLH AADVAQSTHV LLSTPALDAV FTDLEILAAI FAAAIHDVDH
    460 470 480 490 500
    PGVSNQFLIN TNSELALMYN DESVLENHHL AVGFKLLQEE HCDIFQNLTK
    510 520 530 540 550
    KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS SGVLLLDNYT
    560 570 580 590 600
    DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI
    610 620 630 640 650
    SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN
    660 670 680 690 700
    WYQSMIPQSP SPPLDERSRD CQGLMEKFQF ELTLEEEDSE GPEKEGEGPN
    710 720 730
    YFSSTKTLCV IDPENRDSLE ETDIDIATED KSLIDT
    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti178 – 1781I → S in AAL31763 (PubMed:12441002).Curated
    Sequence conflicti178 – 1781I → S in AAL31764 (PubMed:12441002).Curated
    Sequence conflicti178 – 1781I → S in AAH85704 (PubMed:15489334).Curated
    Sequence conflicti531 – 5311T → S in AAA18926 (PubMed:8276818).Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 172172Missing in isoform 2. 3 PublicationsVSP_026678Add
    BLAST
    Alternative sequencei1 – 9393MKKSR…TVSQE → MTAKNSSKELPASESEVCIK TFKEQMRLELELPKLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform 3 and isoform 5. 2 PublicationsVSP_026679Add
    BLAST
    Alternative sequencei1 – 9393MKKSR…TVSQE → MLHVNDLPPPRRHSWI in isoform 4. 1 PublicationVSP_026680Add
    BLAST
    Alternative sequencei173 – 21139LASLR…RVSLQ → MKEQGGTVSGAGSSRGGGDS AMASLQPLQPNYLSVCLFA in isoform 2. 3 PublicationsVSP_004573Add
    BLAST
    Alternative sequencei710 – 73627VIDPE…SLIDT → KPCHAANGLALPVGGGNAAS TQPRCGHV in isoform 5. 1 PublicationVSP_026681Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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

    GeneIDi24626.
    KEGGirno:24626.
    UCSCiRGD:3280. rat. [P14646-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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.

    3D structure databases

    ProteinModelPortaliP14646.
    SMRiP14646. Positions 324-685.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    BindingDBiP14646.
    ChEMBLiCHEMBL2094267.

    PTM databases

    PhosphoSiteiP14646.

    Proteomic databases

    PaxDbiP14646.
    PRIDEiP14646.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi24626.
    KEGGirno:24626.
    UCSCiRGD:3280. rat. [P14646-3]

    Organism-specific databases

    CTDi5142.
    RGDi3280. Pde4b.

    Phylogenomic databases

    eggNOGiNOG122287.
    HOGENOMiHOG000236297.
    HOVERGENiHBG108239.
    InParanoidiP14646.
    KOiK13293.
    OrthoDBiEOG7HQNBC.
    PhylomeDBiP14646.
    TreeFamiTF314638.

    Enzyme and pathway databases

    UniPathwayiUPA00762; UER00747.
    BRENDAi3.1.4.53. 5301.
    ReactomeiREACT_287445. G alpha (s) signalling events.
    REACT_348359. DARPP-32 events.

    Miscellaneous databases

    NextBioi603894.
    PROiP14646.

    Gene expression databases

    ExpressionAtlasiP14646. baseline and differential.
    GenevestigatoriP14646.

    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]
    ProtoNetiSearch...

    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 27, 2015
    This is version 122 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.