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P26687

- TWST1_MOUSE

UniProt

P26687 - TWST1_MOUSE

Protein

Twist-related protein 1

Gene

Twist1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      Previous versions | rss
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    Functioni

    Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation. Represses the activity of the circadian transcriptional activator: NPAS2-ARNTL/BMAL1 heterodimer.5 Publications

    GO - Molecular functioni

    1. E-box binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. protein domain specific binding Source: MGI
    4. protein heterodimerization activity Source: UniProtKB
    5. protein homodimerization activity Source: UniProtKB
    6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    7. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    8. transcription factor binding Source: BHF-UCL

    GO - Biological processi

    1. aortic valve morphogenesis Source: BHF-UCL
    2. cardiac neural crest cell development involved in outflow tract morphogenesis Source: MGI
    3. cardiac neural crest cell migration involved in outflow tract morphogenesis Source: MGI
    4. cell differentiation Source: MGI
    5. cell proliferation involved in heart valve development Source: BHF-UCL
    6. cellular response to growth factor stimulus Source: Ensembl
    7. cellular response to hypoxia Source: BHF-UCL
    8. cranial suture morphogenesis Source: UniProtKB
    9. embryonic camera-type eye formation Source: Ensembl
    10. embryonic cranial skeleton morphogenesis Source: BHF-UCL
    11. embryonic digit morphogenesis Source: MGI
    12. embryonic forelimb morphogenesis Source: MGI
    13. embryonic hindlimb morphogenesis Source: BHF-UCL
    14. embryonic limb morphogenesis Source: MGI
    15. embryonic skeletal system morphogenesis Source: MGI
    16. endocardial cushion morphogenesis Source: MGI
    17. eyelid development in camera-type eye Source: Ensembl
    18. hindlimb morphogenesis Source: MGI
    19. in utero embryonic development Source: MGI
    20. mitral valve morphogenesis Source: BHF-UCL
    21. muscle organ development Source: UniProtKB-KW
    22. negative regulation of apoptotic process Source: MGI
    23. negative regulation of cell differentiation Source: UniProtKB
    24. negative regulation of cellular senescence Source: Ensembl
    25. negative regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
    26. negative regulation of double-strand break repair Source: Ensembl
    27. negative regulation of histone acetylation Source: BHF-UCL
    28. negative regulation of histone phosphorylation Source: Ensembl
    29. negative regulation of molecular function Source: MGI
    30. negative regulation of osteoblast differentiation Source: MGI
    31. negative regulation of oxidative phosphorylation uncoupler activity Source: BHF-UCL
    32. negative regulation of peroxisome proliferator activated receptor signaling pathway Source: BHF-UCL
    33. negative regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
    34. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    35. negative regulation of skeletal muscle tissue development Source: MGI
    36. negative regulation of striated muscle tissue development Source: UniProtKB
    37. negative regulation of transcription, DNA-templated Source: UniProtKB
    38. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    39. negative regulation of tumor necrosis factor production Source: MGI
    40. neural tube closure Source: MGI
    41. neuron migration Source: MGI
    42. odontogenesis Source: Ensembl
    43. ossification Source: MGI
    44. osteoblast differentiation Source: MGI
    45. palate development Source: Ensembl
    46. positive regulation of cell motility Source: BHF-UCL
    47. positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation Source: BHF-UCL
    48. positive regulation of epithelial cell proliferation Source: Ensembl
    49. positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
    50. positive regulation of fatty acid beta-oxidation Source: Ensembl
    51. positive regulation of interleukin-6 secretion Source: Ensembl
    52. positive regulation of monocyte chemotactic protein-1 production Source: Ensembl
    53. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    54. positive regulation of transcription regulatory region DNA binding Source: Ensembl
    55. positive regulation of tumor necrosis factor production Source: Ensembl
    56. regulation of bone mineralization Source: Ensembl
    57. rhythmic process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Developmental protein, Repressor

    Keywords - Biological processi

    Biological rhythms, Differentiation, Myogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Twist-related protein 1
    Alternative name(s):
    M-twist
    Gene namesi
    Name:Twist1
    Synonyms:Twist
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:98872. Twist1.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi179 – 1791C → G: High transactivation activity. 1 Publication
    Mutagenesisi185 – 1851E → D, K or R: High transactivation activity. 1 Publication
    Mutagenesisi186 – 1861R → A or K: High transactivation activity. 1 Publication
    Mutagenesisi187 – 1871L → G: Low transactivation activity. 1 Publication
    Mutagenesisi188 – 1881S → A: High transactivation activity. 1 Publication
    Mutagenesisi191 – 1911F → A, G or P: Low transactivation activity. 1 Publication
    Mutagenesisi192 – 1921S → A: High transactivation activity. 1 Publication
    Mutagenesisi192 – 1921S → P: Intermediate transactivation activity. 1 Publication
    Mutagenesisi195 – 1951R → E: Intermediate transactivation activity. 1 Publication
    Mutagenesisi195 – 1951R → G: Low transactivation activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 206206Twist-related protein 1PRO_0000127488Add
    BLAST

    Proteomic databases

    PRIDEiP26687.

    PTM databases

    PhosphoSiteiP26687.

    Miscellaneous databases

    PMAP-CutDBP26687.

    Expressioni

    Tissue specificityi

    Subset of mesodermal cells.1 Publication

    Inductioni

    By TNF-alpha.1 Publication

    Gene expression databases

    BgeeiP26687.
    CleanExiMM_TWIST1.
    GenevestigatoriP26687.

    Interactioni

    Subunit structurei

    Efficient DNA binding requires dimerization with another bHLH protein. Homodimer or heterodimer with E proteins such as TCF3. ID1 binds preferentially to TCF3 but does not interact efficiently with TWIST1 so ID1 levels control the amount of TCF3 available to dimerize with TWIST1 and thus determine the type of dimer formed.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TP53P046374EBI-6123119,EBI-366083From a different organism.

    Protein-protein interaction databases

    BioGridi204385. 5 interactions.
    IntActiP26687. 5 interactions.
    STRINGi10090.ENSMUSP00000040089.

    Structurei

    3D structure databases

    ProteinModelPortaliP26687.
    SMRiP26687. Positions 113-171.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini112 – 16352bHLHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni165 – 19531Sufficient for transactivation activityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi80 – 10223Gly-richAdd
    BLAST

    Sequence similaritiesi

    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG258515.
    GeneTreeiENSGT00730000110394.
    HOGENOMiHOG000261629.
    InParanoidiP26687.
    KOiK09069.
    OMAiDRQPKRC.
    OrthoDBiEOG7TJ3M9.
    TreeFamiTF315153.

    Family and domain databases

    Gene3Di4.10.280.10. 1 hit.
    InterProiIPR011598. bHLH_dom.
    [Graphical view]
    PfamiPF00010. HLH. 1 hit.
    [Graphical view]
    SMARTiSM00353. HLH. 1 hit.
    [Graphical view]
    SUPFAMiSSF47459. SSF47459. 1 hit.
    PROSITEiPS50888. BHLH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P26687-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMQDVSSSPV SPADDSLSNS EEEPDRQQPA SGKRGARKRR SSRRSAGGSA    50
    GPGGATGGGI GGGDEPGSPA QGKRGKKSAG GGGGGGAGGG GGGGGGSSSG 100
    GGSPQSYEEL QTQRVMANVR ERQRTQSLNE AFAALRKIIP TLPSDKLSKI 150
    QTLKLAARYI DFLYQVLQSD ELDSKMASCS YVAHERLSYA FSVWRMEGAW 200
    SMSASH 206
    Length:206
    Mass (Da):21,198
    Last modified:August 1, 1992 - v1
    Checksum:i618AD8E9BE87C555
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti36 – 361A → R in AAA40515. (PubMed:1840517)Curated
    Sequence conflicti91 – 911G → P in AAA40515. (PubMed:1840517)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M63649 Genomic DNA. Translation: AAA40514.1.
    M63650 mRNA. Translation: AAA40515.1.
    BC033434 mRNA. Translation: AAH33434.1.
    BC083139 mRNA. Translation: AAH83139.1.
    CCDSiCCDS25879.1.
    PIRiI53066.
    RefSeqiNP_035788.1. NM_011658.2.
    UniGeneiMm.3280.

    Genome annotation databases

    EnsembliENSMUST00000049089; ENSMUSP00000040089; ENSMUSG00000035799.
    GeneIDi22160.
    KEGGimmu:22160.
    UCSCiuc007niw.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M63649 Genomic DNA. Translation: AAA40514.1 .
    M63650 mRNA. Translation: AAA40515.1 .
    BC033434 mRNA. Translation: AAH33434.1 .
    BC083139 mRNA. Translation: AAH83139.1 .
    CCDSi CCDS25879.1.
    PIRi I53066.
    RefSeqi NP_035788.1. NM_011658.2.
    UniGenei Mm.3280.

    3D structure databases

    ProteinModelPortali P26687.
    SMRi P26687. Positions 113-171.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204385. 5 interactions.
    IntActi P26687. 5 interactions.
    STRINGi 10090.ENSMUSP00000040089.

    PTM databases

    PhosphoSitei P26687.

    Proteomic databases

    PRIDEi P26687.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000049089 ; ENSMUSP00000040089 ; ENSMUSG00000035799 .
    GeneIDi 22160.
    KEGGi mmu:22160.
    UCSCi uc007niw.1. mouse.

    Organism-specific databases

    CTDi 7291.
    MGIi MGI:98872. Twist1.

    Phylogenomic databases

    eggNOGi NOG258515.
    GeneTreei ENSGT00730000110394.
    HOGENOMi HOG000261629.
    InParanoidi P26687.
    KOi K09069.
    OMAi DRQPKRC.
    OrthoDBi EOG7TJ3M9.
    TreeFami TF315153.

    Miscellaneous databases

    NextBioi 302090.
    PMAP-CutDB P26687.
    PROi P26687.
    SOURCEi Search...

    Gene expression databases

    Bgeei P26687.
    CleanExi MM_TWIST1.
    Genevestigatori P26687.

    Family and domain databases

    Gene3Di 4.10.280.10. 1 hit.
    InterProi IPR011598. bHLH_dom.
    [Graphical view ]
    Pfami PF00010. HLH. 1 hit.
    [Graphical view ]
    SMARTi SM00353. HLH. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47459. SSF47459. 1 hit.
    PROSITEi PS50888. BHLH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes."
      Wolf C., Thisse C., Stoetzel C., Thisse B., Gerlinger P., Perrin-Schmitt F.
      Dev. Biol. 143:363-373(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
    2. "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: Limb.
    3. "The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist."
      Hamamori Y., Wu H.Y., Sartorelli V., Kedes L.
      Mol. Cell. Biol. 17:6563-6573(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    4. "Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity."
      Sosic D., Richardson J.A., Yu K., Ornitz D.M., Olson E.N.
      Cell 112:169-180(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    5. "Histone acetyltransferase-dependent chromatin remodeling and the vascular clock."
      Curtis A.M., Seo S.B., Westgate E.J., Rudic R.D., Smyth E.M., Chakravarti D., FitzGerald G.A., McNamara P.
      J. Biol. Chem. 279:7091-7097(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Twist1 dimer selection regulates cranial suture patterning and fusion."
      Connerney J., Andreeva V., Leshem Y., Muentener C., Mercado M.A., Spicer D.B.
      Dev. Dyn. 235:1345-1357(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    7. "Mechanism of transcriptional activation by the proto-oncogene Twist1."
      Laursen K.B., Mielke E., Iannaccone P., Fuchtbauer E.M.
      J. Biol. Chem. 282:34623-34633(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-179; GLU-185; ARG-186; LEU-187; SER-188; PHE-191; SER-192 AND ARG-195.

    Entry informationi

    Entry nameiTWST1_MOUSE
    AccessioniPrimary (citable) accession number: P26687
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 128 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

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3