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P26687 (TWST1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Twist-related protein 1
Alternative name(s):
M-twist
Gene names
Name:Twist1
Synonyms:Twist
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length206 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subunit structure

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. Ref.6 Ref.7

Subcellular location

Nucleus.

Tissue specificity

Subset of mesodermal cells. Ref.1

Induction

By TNF-alpha. Ref.4

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
   Biological processBiological rhythms
Differentiation
Myogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaortic valve morphogenesis

Inferred from mutant phenotype PubMed 20804746. Source: BHF-UCL

cardiac neural crest cell development involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 18539270. Source: MGI

cardiac neural crest cell migration involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 18539270. Source: MGI

cell differentiation

Inferred from mutant phenotype PubMed 12142027. Source: MGI

cell proliferation involved in heart valve development

Inferred from mutant phenotype PubMed 20804746. Source: BHF-UCL

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from mutant phenotype PubMed 18297062. Source: BHF-UCL

cranial suture morphogenesis

Inferred from mutant phenotype Ref.6. Source: UniProtKB

embryonic camera-type eye formation

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from mutant phenotype PubMed 8988167. Source: BHF-UCL

embryonic digit morphogenesis

Inferred from mutant phenotype PubMed 15030764. Source: MGI

embryonic forelimb morphogenesis

Inferred from mutant phenotype PubMed 12175489. Source: MGI

embryonic hindlimb morphogenesis

Inferred from mutant phenotype PubMed 8988167. Source: BHF-UCL

embryonic limb morphogenesis

Inferred from mutant phenotype PubMed 11350121PubMed 12142027PubMed 15030764. Source: MGI

embryonic skeletal system morphogenesis

Inferred from mutant phenotype PubMed 15030764. Source: MGI

endocardial cushion morphogenesis

Inferred from mutant phenotype PubMed 18539270. Source: MGI

eyelid development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

hindlimb morphogenesis

Inferred from mutant phenotype PubMed 10700192. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 15030764. Source: MGI

mitral valve morphogenesis

Inferred from mutant phenotype PubMed 20804746. Source: BHF-UCL

muscle organ development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 12175489. Source: MGI

negative regulation of cell differentiation

Inferred from direct assay PubMed 9520323. Source: UniProtKB

negative regulation of cellular senescence

Inferred from electronic annotation. Source: Ensembl

negative regulation of double-strand break repair

Inferred from electronic annotation. Source: Ensembl

negative regulation of histone acetylation

Inferred from direct assay PubMed 19345188. Source: BHF-UCL

negative regulation of histone phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of molecular function

Inferred from direct assay PubMed 15030764. Source: MGI

negative regulation of osteoblast differentiation

Inferred from direct assay PubMed 15030764. Source: MGI

negative regulation of oxidative phosphorylation uncoupler activity

Inferred from direct assay PubMed 19345188. Source: BHF-UCL

negative regulation of peroxisome proliferator activated receptor signaling pathway

Inferred from direct assay PubMed 19345188. Source: BHF-UCL

negative regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19345188. Source: BHF-UCL

negative regulation of skeletal muscle tissue development

Inferred from direct assay PubMed 7664846PubMed 7958419. Source: MGI

negative regulation of striated muscle tissue development

Inferred from direct assay PubMed 9520323. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of tumor necrosis factor production

Inferred from genetic interaction PubMed 16831897. Source: MGI

neural tube closure

Inferred from mutant phenotype PubMed 7729687. Source: MGI

neuron migration

Inferred from mutant phenotype PubMed 15162501. Source: MGI

odontogenesis

Inferred from electronic annotation. Source: Ensembl

ossification

Inferred from mutant phenotype PubMed 15030764. Source: MGI

osteoblast differentiation

Inferred from mutant phenotype PubMed 15030764. Source: MGI

palate development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell motility

Inferred from mutant phenotype PubMed 17332324. Source: BHF-UCL

positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation

Inferred from direct assay PubMed 20804746. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype PubMed 17332324PubMed 18297062PubMed 20804746. Source: BHF-UCL

positive regulation of fatty acid beta-oxidation

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of monocyte chemotactic protein-1 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay PubMed 16100003. Source: MGI

   Molecular_functionE-box binding

Inferred from direct assay Ref.6. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Traceable author statement PubMed 11001584. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 22975381. Source: IntAct

protein domain specific binding

Inferred from physical interaction PubMed 15030764. Source: MGI

protein heterodimerization activity

Inferred from direct assay Ref.6. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.6. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.7. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 19345188. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TP53P046374EBI-6123119,EBI-366083From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 206206Twist-related protein 1
PRO_0000127488

Regions

Domain112 – 16352bHLH
Region165 – 19531Sufficient for transactivation activity
Compositional bias80 – 10223Gly-rich

Experimental info

Mutagenesis1791C → G: High transactivation activity. Ref.7
Mutagenesis1851E → D, K or R: High transactivation activity. Ref.7
Mutagenesis1861R → A or K: High transactivation activity. Ref.7
Mutagenesis1871L → G: Low transactivation activity. Ref.7
Mutagenesis1881S → A: High transactivation activity. Ref.7
Mutagenesis1911F → A, G or P: Low transactivation activity. Ref.7
Mutagenesis1921S → A: High transactivation activity. Ref.7
Mutagenesis1921S → P: Intermediate transactivation activity. Ref.7
Mutagenesis1951R → E: Intermediate transactivation activity. Ref.7
Mutagenesis1951R → G: Low transactivation activity. Ref.7
Sequence conflict361A → R in AAA40515. Ref.1
Sequence conflict911G → P in AAA40515. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P26687 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 618AD8E9BE87C555

FASTA20621,198
        10         20         30         40         50         60 
MMQDVSSSPV SPADDSLSNS EEEPDRQQPA SGKRGARKRR SSRRSAGGSA GPGGATGGGI 

        70         80         90        100        110        120 
GGGDEPGSPA QGKRGKKSAG GGGGGGAGGG GGGGGGSSSG GGSPQSYEEL QTQRVMANVR 

       130        140        150        160        170        180 
ERQRTQSLNE AFAALRKIIP TLPSDKLSKI QTLKLAARYI DFLYQVLQSD ELDSKMASCS 

       190        200 
YVAHERLSYA FSVWRMEGAW SMSASH 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63649 Genomic DNA. Translation: AAA40514.1.
M63650 mRNA. Translation: AAA40515.1.
BC033434 mRNA. Translation: AAH33434.1.
BC083139 mRNA. Translation: AAH83139.1.
CCDSCCDS25879.1.
PIRI53066.
RefSeqNP_035788.1. NM_011658.2.
UniGeneMm.3280.

3D structure databases

ProteinModelPortalP26687.
SMRP26687. Positions 113-171.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204385. 5 interactions.
IntActP26687. 5 interactions.
STRING10090.ENSMUSP00000040089.

PTM databases

PhosphoSiteP26687.

Proteomic databases

PRIDEP26687.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000049089; ENSMUSP00000040089; ENSMUSG00000035799.
GeneID22160.
KEGGmmu:22160.
UCSCuc007niw.1. mouse.

Organism-specific databases

CTD7291.
MGIMGI:98872. Twist1.

Phylogenomic databases

eggNOGNOG258515.
GeneTreeENSGT00730000110394.
HOGENOMHOG000261629.
InParanoidP26687.
KOK09069.
OMADRQPKRC.
OrthoDBEOG7TJ3M9.
TreeFamTF315153.

Gene expression databases

BgeeP26687.
CleanExMM_TWIST1.
GenevestigatorP26687.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio302090.
PMAP-CutDBP26687.
PROP26687.
SOURCESearch...

Entry information

Entry nameTWST1_MOUSE
AccessionPrimary (citable) accession number: P26687
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot