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Protein

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

Gene

Pde4b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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: 3',5'-cyclic AMP degradation

    This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
    Proteins known to be involved in this subpathway in this organism are:
    1. High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (Pde4b), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a)
    This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei406Proton donorBy similarity1
    Metal bindingi410Divalent metal cation 1By similarity1
    Metal bindingi446Divalent metal cation 1By similarity1
    Metal bindingi447Divalent metal cation 1By similarity1
    Metal bindingi447Divalent metal cation 2By similarity1
    Binding sitei447cAMPBy similarity1
    Metal bindingi564Divalent metal cation 1By similarity1
    Binding sitei564cAMPBy similarity1
    Sitei567Binds AMP, but not cAMPBy similarity1
    Binding sitei615cAMPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi406 – 410cAMPBy similarity5

    GO - Molecular functioni

    • 3',5'-cyclic-AMP phosphodiesterase activity Source: RGD
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • cAMP catabolic process Source: RGD
    • signal transduction Source: InterPro

    Keywordsi

    Molecular functionHydrolase
    LigandcAMP, Metal-binding

    Enzyme and pathway databases

    BRENDAi3.1.4.53 5301
    ReactomeiR-RNO-180024 DARPP-32 events
    R-RNO-418555 G alpha (s) signalling 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 5

    Organism-specific databases

    RGDi3280 Pde4b

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Chemistry databases

    ChEMBLiCHEMBL3382

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001988101 – 736cAMP-specific 3',5'-cyclic phosphodiesterase 4BAdd BLAST736

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei290PhosphoserineCombined sources1
    Modified residuei659PhosphoserineCombined sources1
    Modified residuei661PhosphoserineCombined sources1
    Isoform 4 (identifier: P14646-4)
    Modified residuei56Phosphoserine1 Publication1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP14646
    PRIDEiP14646

    PTM databases

    iPTMnetiP14646
    PhosphoSitePlusiP14646

    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

    BgeeiENSRNOG00000005905
    ExpressionAtlasiP14646 baseline and differential

    Interactioni

    Protein-protein interaction databases

    BioGridi246764, 1 interactor
    STRINGi10116.ENSRNOP00000007738

    Chemistry databases

    BindingDBiP14646

    Structurei

    3D structure databases

    ProteinModelPortaliP14646
    SMRiP14646
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini330 – 659PDEasePROSITE-ProRule annotationAdd BLAST330

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3689 Eukaryota
    ENOG410XRI7 LUCA
    GeneTreeiENSGT00760000118889
    HOGENOMiHOG000236297
    HOVERGENiHBG108239
    InParanoidiP14646
    KOiK13293
    PhylomeDBiP14646
    TreeFamiTF314638

    Family and domain databases

    CDDicd00077 HDc, 1 hit
    Gene3Di1.10.1300.10, 1 hit
    InterProiView protein in InterPro
    IPR003607 HD/PDEase_dom
    IPR023088 PDEase
    IPR002073 PDEase_catalytic_dom
    IPR036971 PDEase_catalytic_dom_sf
    IPR023174 PDEase_CS
    PfamiView protein in Pfam
    PF00233 PDEase_I, 1 hit
    PRINTSiPR00387 PDIESTERASE1
    SMARTiView protein in SMART
    SM00471 HDc, 1 hit
    PROSITEiView protein in PROSITE
    PS00126 PDEASE_I_1, 1 hit
    PS51845 PDEASE_I_2, 1 hit

    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: Activated by phosphorylation at Ser-56. Mutagenesis of Ser-56 abolishes activation.1 Publication
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti178I → S in AAL31763 (PubMed:12441002).Curated1
    Sequence conflicti178I → S in AAL31764 (PubMed:12441002).Curated1
    Sequence conflicti178I → S in AAH85704 (PubMed:15489334).Curated1
    Sequence conflicti531T → S in AAA18926 (PubMed:8276818).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0266781 – 172Missing in isoform 2. 3 PublicationsAdd BLAST172
    Alternative sequenceiVSP_0266791 – 93MKKSR…TVSQE → MTAKNSSKELPASESEVCIK TFKEQMRLELELPKLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform 3 and isoform 5. 2 PublicationsAdd BLAST93
    Alternative sequenceiVSP_0266801 – 93MKKSR…TVSQE → MLHVNDLPPPRRHSWI in isoform 4. 1 PublicationAdd BLAST93
    Alternative sequenceiVSP_004573173 – 211LASLR…RVSLQ → MKEQGGTVSGAGSSRGGGDS AMASLQPLQPNYLSVCLFA in isoform 2. 3 PublicationsAdd BLAST39
    Alternative sequenceiVSP_026681710 – 736VIDPE…SLIDT → KPCHAANGLALPVGGGNAAS TQPRCGHV in isoform 5. 1 PublicationAdd BLAST27

    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

    EnsembliENSRNOT00000007738; ENSRNOP00000007738; ENSRNOG00000005905 [P14646-2]
    GeneIDi24626
    KEGGirno:24626
    UCSCiRGD:3280 rat [P14646-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiPDE4B_RAT
    AccessioniPrimary (citable) accession number: P14646
    Secondary accession number(s): Q5RKL0, Q8VD81, Q8VD82
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: July 10, 2007
    Last modified: May 23, 2018
    This is version 144 of the entry and version 4 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

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