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P26651

- TTP_HUMAN

UniProt

P26651 - TTP_HUMAN

Protein

Tristetraprolin

Gene

ZFP36

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      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). Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri103 – 13129C3H1-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri141 – 16929C3H1-type 2PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. 14-3-3 protein binding Source: UniProtKB
    2. AU-rich element binding Source: UniProtKB
    3. C-C chemokine binding Source: UniProtKB
    4. DNA binding Source: UniProtKB-KW
    5. metal ion binding Source: UniProtKB-KW
    6. mRNA binding Source: MGI
    7. poly(A) RNA binding Source: UniProtKB
    8. protein binding Source: UniProtKB
    9. protein kinase binding Source: UniProtKB
    10. single-stranded RNA binding Source: ProtInc

    GO - Biological processi

    1. 3'-UTR-mediated mRNA stabilization Source: UniProtKB
    2. gene expression Source: Reactome
    3. mRNA catabolic process Source: UniProtKB
    4. mRNA metabolic process Source: Reactome
    5. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    6. negative regulation of translation involved in gene silencing by miRNA Source: UniProtKB
    7. nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
    8. positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
    9. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
    10. regulation of tumor necrosis factor production Source: UniProtKB
    11. response to starvation Source: UniProtKB
    12. RNA metabolic process Source: Reactome

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
    SignaLinkiP26651.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tristetraprolin
    Short name:
    TTP
    Alternative name(s):
    G0/G1 switch regulatory protein 24
    Growth factor-inducible nuclear protein NUP475
    Protein TIS11A
    Short name:
    TIS11
    Zinc finger protein 36 homolog
    Short name:
    Zfp-36
    Gene namesi
    Name:ZFP36
    Synonyms:G0S24, RNF162A, TIS11A, TTP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:12862. 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.

    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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi60 – 601S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-186. 1 Publication
    Mutagenesisi186 – 1861S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-60. 1 Publication
    Mutagenesisi315 – 3151R → A: Abolishes interaction with CNOT1. 1 Publication
    Mutagenesisi319 – 3191F → A: Abolishes interaction with CNOT1 and impairs TNF mRNA deadenylation. 1 Publication

    Organism-specific databases

    PharmGKBiPA37451.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 326326TristetraprolinPRO_0000089163Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei60 – 601Phosphoserine; by MAPKAPK21 Publication
    Modified residuei66 – 661Phosphoserine1 Publication
    Modified residuei88 – 881Phosphoserine1 Publication
    Modified residuei90 – 901PhosphoserineBy similarity
    Modified residuei92 – 921Phosphothreonine1 Publication
    Modified residuei93 – 931PhosphoserineBy similarity
    Modified residuei169 – 1691Phosphoserine1 Publication
    Modified residuei186 – 1861Phosphoserine; by MAPKAPK23 Publications
    Modified residuei197 – 1971Phosphoserine1 Publication
    Modified residuei218 – 2181Phosphoserine1 Publication
    Modified residuei228 – 2281Phosphoserine1 Publication
    Modified residuei276 – 2761Phosphoserine1 Publication
    Modified residuei296 – 2961Phosphoserine1 Publication
    Modified residuei323 – 3231PhosphoserineBy similarity

    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.3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP26651.
    PRIDEiP26651.

    PTM databases

    PhosphoSiteiP26651.

    Expressioni

    Inductioni

    By stimulation with various mitogens.

    Gene expression databases

    ArrayExpressiP26651.
    BgeeiP26651.
    CleanExiHS_ZFP36.
    GenevestigatoriP26651.

    Organism-specific databases

    HPAiHPA006009.

    Interactioni

    Subunit structurei

    Interacts (via C-terminus) with CNOT1.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DCP1AQ9NPI62EBI-374248,EBI-374238
    EDC3Q96F862EBI-374248,EBI-997311

    Protein-protein interaction databases

    BioGridi113370. 28 interactions.
    DIPiDIP-29845N.
    IntActiP26651. 20 interactions.
    MINTiMINT-1171915.
    STRINGi9606.ENSP00000248673.

    Structurei

    Secondary structure

    1
    326
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi317 – 3226

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4J8SX-ray1.55B312-326[»]
    ProteinModelPortaliP26651.
    SMRiP26651. Positions 99-170.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati71 – 755P-P-P-P-G
    Repeati198 – 2025P-P-P-P-G
    Repeati219 – 2235P-P-P-P-G

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni312 – 32615Interaction with CNOT1Add
    BLAST

    Sequence similaritiesi

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

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri103 – 13129C3H1-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri141 – 16929C3H1-type 2PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5063.
    HOGENOMiHOG000233479.
    HOVERGENiHBG008483.
    InParanoidiP26651.
    KOiK15308.
    OrthoDBiEOG76QFJP.
    PhylomeDBiP26651.
    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.

    P26651-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDLTAIYESL LSLSPDVPVP SDHGGTESSP GWGSSGPWSL SPSDSSPSGV    50
    TSRLPGRSTS LVEGRSCGWV PPPPGFAPLA PRLGPELSPS PTSPTATSTT 100
    PSRYKTELCR TFSESGRCRY GAKCQFAHGL GELRQANRHP KYKTELCHKF 150
    YLQGRCPYGS RCHFIHNPSE DLAAPGHPPV LRQSISFSGL PSGRRTSPPP 200
    PGLAGPSLSS SSFSPSSSPP PPGDLPLSPS AFSAAPGTPL ARRDPTPVCC 250
    PSCRRATPIS VWGPLGGLVR TPSVQSLGSD PDEYASSGSS LGGSDSPVFE 300
    AGVFAPPQPV AAPRRLPIFN RISVSE 326
    Length:326
    Mass (Da):34,003
    Last modified:August 1, 1992 - v1
    Checksum:iDDD9AD950AF7AF98
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti37 – 371P → S.1 Publication
    Corresponds to variant rs17878633 [ dbSNP | Ensembl ].
    VAR_021064
    Natural varianti55 – 551P → S.
    Corresponds to variant rs2229272 [ dbSNP | Ensembl ].
    VAR_052324
    Natural varianti259 – 2591I → F.1 Publication
    Corresponds to variant rs17886974 [ dbSNP | Ensembl ].
    VAR_021065
    Natural varianti324 – 3241V → F.1 Publication
    Corresponds to variant rs17884899 [ dbSNP | Ensembl ].
    VAR_021066

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M92843 mRNA. Translation: AAA58489.1.
    M92844 Genomic DNA. Translation: AAC37600.1.
    M63625 mRNA. Translation: AAA61240.1.
    AK314042 mRNA. Translation: BAG36751.1.
    AY771351 Genomic DNA. Translation: AAV28731.1.
    BC009693 mRNA. Translation: AAH09693.1.
    PIRiS34427.
    RefSeqiNP_003398.2. NM_003407.3.
    UniGeneiHs.534052.

    Genome annotation databases

    EnsembliENST00000248673; ENSP00000248673; ENSG00000128016.
    GeneIDi7538.
    KEGGihsa:7538.
    UCSCiuc002olh.2. human.

    Polymorphism databases

    DMDMi136471.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M92843 mRNA. Translation: AAA58489.1 .
    M92844 Genomic DNA. Translation: AAC37600.1 .
    M63625 mRNA. Translation: AAA61240.1 .
    AK314042 mRNA. Translation: BAG36751.1 .
    AY771351 Genomic DNA. Translation: AAV28731.1 .
    BC009693 mRNA. Translation: AAH09693.1 .
    PIRi S34427.
    RefSeqi NP_003398.2. NM_003407.3.
    UniGenei Hs.534052.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4J8S X-ray 1.55 B 312-326 [» ]
    ProteinModelPortali P26651.
    SMRi P26651. Positions 99-170.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113370. 28 interactions.
    DIPi DIP-29845N.
    IntActi P26651. 20 interactions.
    MINTi MINT-1171915.
    STRINGi 9606.ENSP00000248673.

    PTM databases

    PhosphoSitei P26651.

    Polymorphism databases

    DMDMi 136471.

    Proteomic databases

    PaxDbi P26651.
    PRIDEi P26651.

    Protocols and materials databases

    DNASUi 7538.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000248673 ; ENSP00000248673 ; ENSG00000128016 .
    GeneIDi 7538.
    KEGGi hsa:7538.
    UCSCi uc002olh.2. human.

    Organism-specific databases

    CTDi 7538.
    GeneCardsi GC19P039897.
    HGNCi HGNC:12862. ZFP36.
    HPAi HPA006009.
    MIMi 190700. gene.
    neXtProti NX_P26651.
    PharmGKBi PA37451.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5063.
    HOGENOMi HOG000233479.
    HOVERGENi HBG008483.
    InParanoidi P26651.
    KOi K15308.
    OrthoDBi EOG76QFJP.
    PhylomeDBi P26651.
    TreeFami TF315463.

    Enzyme and pathway databases

    Reactomei REACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
    SignaLinki P26651.

    Miscellaneous databases

    ChiTaRSi ZFP36. human.
    GeneWikii ZFP36.
    GenomeRNAii 7538.
    NextBioi 29497.
    PROi P26651.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P26651.
    Bgeei P26651.
    CleanExi HS_ZFP36.
    Genevestigatori P26651.

    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. "The human TTP protein: sequence, alignment with related proteins, and chromosomal localization of the mouse and human genes."
      Taylor G.A., Lai W.S., Oakey R.J., Seldin M.F., Shows T.B., Eddy R.L. Jr., Blackshear P.J.
      Nucleic Acids Res. 19:3454-3454(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Uterus.
    3. NIEHS SNPs program
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-37; PHE-259 AND PHE-324.
    4. "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].
      Tissue: Pancreas.
    5. "MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay."
      Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K., Anderson P.
      EMBO J. 23:1313-1324(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-60 AND SER-186 BY MAPKAPK2, SUBCELLULAR LOCATION, RNA-BINDING, FUNCTION, MUTAGENESIS OF SER-60 AND SER-186.
    6. "Identification of the anti-inflammatory protein tristetraprolin as a hyperphosphorylated protein by mass spectrometry and site-directed mutagenesis."
      Cao H., Deterding L.J., Venable J.D., Kennington E.A., Yates J.R. III, Tomer K.B., Blackshear P.J.
      Biochem. J. 394:285-297(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-66; SER-88; THR-92; SER-169; SER-186; SER-197; SER-218; SER-228; SER-276 AND SER-296.
    7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin."
      Fabian M.R., Frank F., Rouya C., Siddiqui N., Lai W.S., Karetnikov A., Blackshear P.J., Nagar B., Sonenberg N.
      Nat. Struct. Mol. Biol. 20:735-739(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 312-326 IN COMPLEX WITH CNOT1, INTERACTION WITH CNOT1, FUNCTION, MUTAGENESIS OF ARG-315 AND PHE-319.

    Entry informationi

    Entry nameiTTP_HUMAN
    AccessioniPrimary (citable) accession number: P26651
    Secondary accession number(s): B2RA54
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3