Tribbles homolog 1

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• mitogen-activated protein kinase kinase binding Source: BHF-UCL <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• protein kinase inhibitor activity Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
• transcription factor binding Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency."
    Yamamoto M., Uematsu S., Okamoto T., Matsuura Y., Sato S., Kumar H., Satoh T., Saitoh T., Takeda K., Ishii K.J., Takeuchi O., Kawai T., Akira S.
    J. Exp. Med. 204:2233-2239(2007) [PubMed] [Europe PMC] [Abstract]
• ubiquitin protein ligase binding Source: BHF-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • Ref.10

    "Differential ability of Tribbles family members to promote degradation of C/EBPalpha and induce acute myelogenous leukemia."
    Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.
    Blood 116:1321-1328(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CEBPA AND COP1.
• ubiquitin-protein transferase regulator activity Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • Ref.10

    "Differential ability of Tribbles family members to promote degradation of C/EBPalpha and induce acute myelogenous leukemia."
    Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.
    Blood 116:1321-1328(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CEBPA AND COP1.

GO - Biological processⁱ

• JNK cascade Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA-binding transcription factor activity Source: BHF-UCLInferred from mutant phenotypeⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
• negative regulation of lipopolysaccharide-mediated signaling pathway Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neutrophil differentiation Source: Ensembl
• negative regulation of protein kinase activity Source: BHF-UCLInferred from mutant phenotypeⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
• negative regulation of smooth muscle cell migration Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of smooth muscle cell proliferation Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of eosinophil differentiation Source: Ensembl
• positive regulation of macrophage differentiation Source: Ensembl
• positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • Ref.10

    "Differential ability of Tribbles family members to promote degradation of C/EBPalpha and induce acute myelogenous leukemia."
    Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.
    Blood 116:1321-1328(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CEBPA AND COP1.
• regulation of MAP kinase activity Source: UniProtKBInferred from direct assayⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
• response to lipopolysaccharide Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Mutagenesis

Organism-specific databases

Miscellaneous databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• mitogen-activated protein kinase kinase binding Source: BHF-UCLInferred from direct assayⁱ
  • Ref.1

    "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades."
    Kiss-Toth E., Bagstaff S.M., Sung H.Y., Jozsa V., Dempsey C., Caunt J.C., Oxley K.M., Wyllie D.H., Polgar T., Harte M., O'Neill L.A.J., Qwarnstrom E.E., Dower S.K.
    J. Biol. Chem. 279:42703-42708(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP2K1 AND MAP2K4.
  • "Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways."
    Sung H.Y., Guan H., Czibula A., King A.R., Eder K., Heath E., Suvarna S.K., Dower S.K., Wilson A.G., Francis S.E., Crossman D.C., Kiss-Toth E.
    J. Biol. Chem. 282:18379-18387(2007) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency."
    Yamamoto M., Uematsu S., Okamoto T., Matsuura Y., Sato S., Kumar H., Satoh T., Saitoh T., Takeda K., Ishii K.J., Takeuchi O., Kawai T., Akira S.
    J. Exp. Med. 204:2233-2239(2007) [PubMed] [Europe PMC] [Abstract]
• ubiquitin protein ligase binding Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • Ref.10

    "Differential ability of Tribbles family members to promote degradation of C/EBPalpha and induce acute myelogenous leukemia."
    Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.
    Blood 116:1321-1328(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CEBPA AND COP1.

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Motif

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MRVGPVRSAM SGASQPRGPA LLFPATRGVP AKRLLDADDA AAVAAKCPRL 
        60         70         80         90        100
SECSSPPDYL SPPGSPCSPQ PPPAAPGAGG GSGSAPGPSR IADYLLLPLA 
       110        120        130        140        150
EREHVSRALC IHTGRELRCK VFPIKHYQDK IRPYIQLPSH SNITGIVEVI 
       160        170        180        190        200
LGETKAYVFF EKDFGDMHSY VRSRKRLREE EAARLFKQIV SAVAHCHQSA 
       210        220        230        240        250
IVLGDLKLRK FVFSTEERTQ LRLESLEDTH IMKGEDDALS DKHGCPAYVS 
       260        270        280        290        300
PEILNTTGTY SGKAADVWSL GVMLYTLLVG RYPFHDSDPS ALFSKIRRGQ 
       310        320        330        340        350
FCIPEHISPK ARCLIRSLLR REPSERLTAP EILLHPWFES VLEPGYIDSE 
       360        370 
IGTSDQIVPE YQEDSDISSF FC                               

        10         20         30         40         50
MHSYVRSRKR LREEEAARLF KQIVSAVAHC HQSAIVLGDL KLRKFVFSTE 
        60         70         80         90        100
ERTQLRLESL EDTHIMKGED DALSDKHGCP AYVSPEILNT TGTYSGKAAD 
       110        120        130        140        150
VWSLGVMLYT LLVGRYPFHD SDPSALFSKI RRGQFCIPEH ISPKARCLIR 
       160        170        180        190        200
SLLRREPSER LTAPEILLHP WFESVLEPGY IDSEIGTSDQ IVPEYQEDSD 

ISSFFC                                                 

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
2. SIMILARITY comments
   Index of protein domains and families
3. Human entries with polymorphisms or disease mutations
   List of human entries with polymorphisms or disease mutations
4. Human polymorphisms and disease mutations
   Index of human polymorphisms and disease mutations
5. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
6. Human chromosome 8
   Human chromosome 8: entries, gene names and cross-references to MIM
7. Human and mouse protein kinases
   Human and mouse protein kinases: classification and index