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P22893

- TTP_MOUSE

UniProt

P22893 - TTP_MOUSE

Protein

Tristetraprolin

Gene

Zfp36

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Aug 1991)
      Previous versions | rss
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    Functioni

    mRNA-binding protein involved in post-transcriptional regulation of AU-rich element (ARE)-containing mRNAs. Acts by specifically binding ARE-containing mRNAs and promoting their degradation. Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri95 – 12329C3H1-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri133 – 16129C3H1-type 2PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. 14-3-3 protein binding Source: UniProtKB
    2. AU-rich element binding Source: UniProtKB
    3. DNA binding Source: UniProtKB-KW
    4. metal ion binding Source: UniProtKB-KW
    5. mRNA 3'-UTR AU-rich region binding Source: MGI
    6. mRNA binding Source: MGI
    7. protein binding Source: IntAct

    GO - Biological processi

    1. 3'-UTR-mediated mRNA stabilization Source: UniProtKB
    2. intracellular signal transduction Source: MGI
    3. mRNA catabolic process Source: UniProtKB
    4. negative regulation of inflammatory response Source: UniProtKB
    5. negative regulation of myeloid cell differentiation Source: MGI
    6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    7. negative regulation of translation involved in gene silencing by miRNA Source: UniProtKB
    8. nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: MGI
    9. nuclear-transcribed mRNA poly(A) tail shortening Source: MGI
    10. positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
    11. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
    12. regulation of mRNA stability Source: MGI
    13. regulation of transcription from RNA polymerase II promoter Source: MGI
    14. regulation of tumor necrosis factor production Source: UniProtKB
    15. response to starvation Source: UniProtKB
    16. RNA destabilization Source: MGI

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_198689. Tristetraprolin (TTP) destabilizes mRNA.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tristetraprolin
    Short name:
    TTP
    Alternative name(s):
    Growth factor-inducible nuclear protein NUP475
    Protein TIS11A
    Short name:
    TIS11
    TPA-induced sequence 11
    Zinc finger protein 36
    Short name:
    Zfp-36
    Gene namesi
    Name:Zfp36
    Synonyms:Tis11, Tis11a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:99180. Zfp36.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication
    Note: Localizes to stress granules upon energy starvation. phosphorylation by MAPKAPK2 promotes exclusion from stress granules By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytoplasmic stress granule Source: UniProtKB
    3. cytosol Source: MGI
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 319319TristetraprolinPRO_0000089164Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei52 – 521Phosphoserine; by MAPKAPK21 Publication
    Modified residuei58 – 581PhosphoserineBy similarity
    Modified residuei80 – 801Phosphoserine1 Publication
    Modified residuei82 – 821Phosphoserine1 Publication
    Modified residuei84 – 841PhosphothreonineBy similarity
    Modified residuei85 – 851Phosphoserine1 Publication
    Modified residuei178 – 1781Phosphoserine; by MAPKAPK21 Publication
    Modified residuei189 – 1891PhosphoserineBy similarity
    Modified residuei210 – 2101PhosphoserineBy similarity
    Modified residuei220 – 2201Phosphoserine; by MAPK; in vitro1 Publication
    Modified residuei250 – 2501Phosphothreonine1 Publication
    Modified residuei269 – 2691PhosphoserineBy similarity
    Modified residuei289 – 2891PhosphoserineBy similarity
    Modified residuei316 – 3161Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylation by MAPKAPK2 increases its stability and binding to 14-3-3 proteins, leading to reduce its ARE affinity leading to inhibition of degradation of ARE-containing transcripts. Phosphorylated upon mitogen stimulation.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiP22893.

    PTM databases

    PhosphoSiteiP22893.

    Expressioni

    Tissue specificityi

    Especially abundant in intestine, thymus and regenerating liver, and in macrophage cell line stimulated by gamma-interferon.

    Inductioni

    By growth factors and by extracellular signaling agents.

    Gene expression databases

    ArrayExpressiP22893.
    BgeeiP22893.
    CleanExiMM_ZFP36.
    GenevestigatoriP22893.

    Interactioni

    Subunit structurei

    Interacts with CNOT1.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CNOT1A5YKK65EBI-647803,EBI-1222758From a different organism.
    CNOT7Q9UIV13EBI-647803,EBI-2105113From a different organism.
    YWHABP319465EBI-647803,EBI-359815From a different organism.

    Protein-protein interaction databases

    BioGridi204658. 3 interactions.
    IntActiP22893. 34 interactions.
    MINTiMINT-225240.

    Structurei

    Secondary structure

    1
    319
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi103 – 1064
    Turni111 – 1155
    Beta strandi120 – 1223
    Helixi125 – 1273

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M9ONMR-A91-163[»]
    ProteinModelPortaliP22893.
    SMRiP22893. Positions 91-162.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22893.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati63 – 675P-P-P-P-G
    Repeati190 – 1945P-P-P-P-G
    Repeati211 – 2155P-P-P-P-G

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni305 – 31915Interaction with CNOT1By similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 2 C3H1-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri95 – 12329C3H1-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri133 – 16129C3H1-type 2PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5063.
    HOGENOMiHOG000233479.
    HOVERGENiHBG008483.
    InParanoidiP22893.
    KOiK15308.
    OMAiNRISVSE.
    OrthoDBiEOG76QFJP.
    PhylomeDBiP22893.
    TreeFamiTF315463.

    Family and domain databases

    Gene3Di4.10.1000.10. 2 hits.
    InterProiIPR000571. Znf_CCCH.
    [Graphical view]
    PfamiPF00642. zf-CCCH. 2 hits.
    [Graphical view]
    SMARTiSM00356. ZnF_C3H1. 2 hits.
    [Graphical view]
    PROSITEiPS50103. ZF_C3H1. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P22893-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDLSAIYESL QSMSHDLSSD HGGTESLGGL WNINSDSIPS GVTSRLTGRS    50
    TSLVEGRSCG WVPPPPGFAP LAPRPGPELS PSPTSPTATP TTSSRYKTEL 100
    CRTYSESGRC RYGAKCQFAH GLGELRQANR HPKYKTELCH KFYLQGRCPY 150
    GSRCHFIHNP TEDLALPGQP HVLRQSISFS GLPSGRRSSP PPPGFSGPSL 200
    SSCSFSPSSS PPPPGDLPLS PSAFSAAPGT PVTRRDPNQA CCPSCRRSTT 250
    PSTIWGPLGG LARSPSAHSL GSDPDDYASS GSSLGGSDSP VFEAGVFGPP 300
    QTPAPPRRLP IFNRISVSE 319
    Length:319
    Mass (Da):33,613
    Last modified:August 1, 1991 - v1
    Checksum:i860DD6DDA80386F8
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57422 mRNA. Translation: AAA40498.1.
    M58691 mRNA. Translation: AAA39837.1.
    X14678 mRNA. Translation: CAA32807.1. Sequence problems.
    M58565 mRNA. Translation: AAA72947.1.
    L42317 Genomic DNA. Translation: AAC37676.1.
    BC021391 mRNA. Translation: AAH21391.1.
    CCDSiCCDS21041.1.
    PIRiA36600.
    S04743.
    RefSeqiNP_035886.1. NM_011756.4.
    UniGeneiMm.389856.

    Genome annotation databases

    EnsembliENSMUST00000051241; ENSMUSP00000057815; ENSMUSG00000044786.
    GeneIDi22695.
    KEGGimmu:22695.
    UCSCiuc009fys.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57422 mRNA. Translation: AAA40498.1 .
    M58691 mRNA. Translation: AAA39837.1 .
    X14678 mRNA. Translation: CAA32807.1 . Sequence problems.
    M58565 mRNA. Translation: AAA72947.1 .
    L42317 Genomic DNA. Translation: AAC37676.1 .
    BC021391 mRNA. Translation: AAH21391.1 .
    CCDSi CCDS21041.1.
    PIRi A36600.
    S04743.
    RefSeqi NP_035886.1. NM_011756.4.
    UniGenei Mm.389856.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1M9O NMR - A 91-163 [» ]
    ProteinModelPortali P22893.
    SMRi P22893. Positions 91-162.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204658. 3 interactions.
    IntActi P22893. 34 interactions.
    MINTi MINT-225240.

    PTM databases

    PhosphoSitei P22893.

    Proteomic databases

    PRIDEi P22893.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000051241 ; ENSMUSP00000057815 ; ENSMUSG00000044786 .
    GeneIDi 22695.
    KEGGi mmu:22695.
    UCSCi uc009fys.1. mouse.

    Organism-specific databases

    CTDi 7538.
    MGIi MGI:99180. Zfp36.

    Phylogenomic databases

    eggNOGi COG5063.
    HOGENOMi HOG000233479.
    HOVERGENi HBG008483.
    InParanoidi P22893.
    KOi K15308.
    OMAi NRISVSE.
    OrthoDBi EOG76QFJP.
    PhylomeDBi P22893.
    TreeFami TF315463.

    Enzyme and pathway databases

    Reactomei REACT_198689. Tristetraprolin (TTP) destabilizes mRNA.

    Miscellaneous databases

    EvolutionaryTracei P22893.
    NextBioi 303151.
    PROi P22893.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22893.
    Bgeei P22893.
    CleanExi MM_ZFP36.
    Genevestigatori P22893.

    Family and domain databases

    Gene3Di 4.10.1000.10. 2 hits.
    InterProi IPR000571. Znf_CCCH.
    [Graphical view ]
    Pfami PF00642. zf-CCCH. 2 hits.
    [Graphical view ]
    SMARTi SM00356. ZnF_C3H1. 2 hits.
    [Graphical view ]
    PROSITEi PS50103. ZF_C3H1. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich protein."
      Lai W.S., Stumpo D.J., Blackshear P.J.
      J. Biol. Chem. 265:16556-16563(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence."
      Dubois R.N., McLane M.W., Ryder K., Lau L.F., Nathans D.
      J. Biol. Chem. 265:19185-19191(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate."
      Varnum B.C., Lim R.W., Sukhatme V.P., Herschman H.R.
      Oncogene 4:119-120(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Swiss.
    4. "A corrected sequence for the predicted protein from the mitogen-inducible TIS11 primary response gene."
      Ma Q., Herschman H.R.
      Oncogene 6:1277-1278(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    5. "The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat."
      Varnum B.C., Ma Q., Chi T., Fletcher B.S., Herschman H.R.
      Mol. Cell. Biol. 11:1754-1758(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
    6. "Promoter analysis of Zfp-36, the mitogen-inducible gene encoding the zinc finger protein tristetraprolin."
      Lai W.S., Thompson M.J., Taylor G.A., Liu Y., Blackshear P.J.
      J. Biol. Chem. 270:25266-25272(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: BALB/c.
      Tissue: Liver.
    7. "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].
      Strain: FVB/N.
      Tissue: Liver.
    8. "Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro."
      Taylor G.A., Thompson M.J., Lai W.S., Blackshear P.J.
      J. Biol. Chem. 270:13341-13347(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-220.
    9. "Members of the tristetraprolin family of tandem CCCH zinc finger proteins exhibit CRM1-dependent nucleocytoplasmic shuttling."
      Phillips R.S., Ramos S.B., Blackshear P.J.
      J. Biol. Chem. 277:11606-11613(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    10. "MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding."
      Chrestensen C.A., Schroeder M.J., Shabanowitz J., Hunt D.F., Pelo J.W., Worthington M.T., Sturgill T.W.
      J. Biol. Chem. 279:10176-10184(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, PHOSPHORYLATION AT SER-52; SER-80; SER-82; SER-85; SER-178; THR-250 AND SER-316, IDENTIFICATION BY MASS SPECTROMETRY.
    11. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. "Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin."
      Sandler H., Kreth J., Timmers H.T., Stoecklin G.
      Nucleic Acids Res. 39:4373-4386(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CNOT1.
    13. "A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold with a disklike structure."
      Amann B.T., Worthington M.T., Berg J.M.
      Biochemistry 42:217-221(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 91-163 IN COMPLEX WITH ZINC.

    Entry informationi

    Entry nameiTTP_MOUSE
    AccessioniPrimary (citable) accession number: P22893
    Secondary accession number(s): P11520
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: October 1, 2014
    This is version 143 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3