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Q62231

- SIX1_MOUSE

UniProt

Q62231 - SIX1_MOUSE

Protein

Homeobox protein SIX1

Gene

Six1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (13 Apr 2004)
      Previous versions | rss
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    Functioni

    Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development. Plays an important role in the development of several organs, including kidney, muscle and inner ear. Depending on context, functions as transcriptional repressor or activator. Lacks an activation domain, and requires interaction with EYA family members for transcription activation. Mediates nuclear translocation of EYA1 and EYA2. Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter. Regulates the expression of numerous genes, including MYC, CCNA1, CCND1 and EZR. Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2. Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex. During myogenesis, seems to act together with EYA2 and DACH2.8 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi124 – 18360HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. protein binding Source: UniProtKB
    3. sequence-specific DNA binding Source: MGI
    4. sequence-specific DNA binding transcription factor activity Source: MGI
    5. transcription regulatory region DNA binding Source: Ensembl

    GO - Biological processi

    1. anatomical structure development Source: MGI
    2. aorta morphogenesis Source: MGI
    3. apoptotic process Source: UniProtKB-KW
    4. branching involved in ureteric bud morphogenesis Source: MGI
    5. cochlea morphogenesis Source: MGI
    6. embryonic cranial skeleton morphogenesis Source: MGI
    7. embryonic skeletal system morphogenesis Source: MGI
    8. epithelial cell differentiation Source: MGI
    9. facial nerve morphogenesis Source: MGI
    10. generation of neurons Source: UniProtKB
    11. inner ear development Source: UniProtKB
    12. inner ear morphogenesis Source: MGI
    13. kidney development Source: UniProtKB
    14. mesonephric tubule formation Source: UniProtKB
    15. metanephric mesenchyme development Source: UniProtKB
    16. middle ear morphogenesis Source: MGI
    17. myoblast migration Source: MGI
    18. negative regulation of branching involved in ureteric bud morphogenesis Source: MGI
    19. negative regulation of neuron apoptotic process Source: UniProtKB
    20. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    21. neuron fate specification Source: MGI
    22. organ induction Source: MGI
    23. otic vesicle development Source: MGI
    24. outflow tract morphogenesis Source: MGI
    25. pattern specification process Source: MGI
    26. pharyngeal system development Source: MGI
    27. positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
    28. positive regulation of mesenchymal cell proliferation involved in ureter development Source: MGI
    29. positive regulation of secondary heart field cardioblast proliferation Source: MGI
    30. positive regulation of transcription, DNA-templated Source: UniProtKB
    31. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    32. positive regulation of ureteric bud formation Source: UniProtKB
    33. protein localization to nucleus Source: Ensembl
    34. regulation of branch elongation involved in ureteric bud branching Source: UniProtKB
    35. regulation of gene expression Source: MGI
    36. regulation of neuron differentiation Source: MGI
    37. regulation of protein localization Source: MGI
    38. regulation of synaptic growth at neuromuscular junction Source: MGI
    39. regulation of transcription, DNA-templated Source: MGI
    40. renal system development Source: MGI
    41. sensory perception of sound Source: MGI
    42. skeletal muscle tissue development Source: MGI
    43. skeletal system morphogenesis Source: MGI
    44. thymus development Source: MGI
    45. thyroid gland development Source: MGI
    46. transcription, DNA-templated Source: UniProtKB-KW
    47. ureteric bud development Source: MGI
    48. ureter smooth muscle cell differentiation Source: MGI

    Keywords - Molecular functioni

    Activator, Developmental protein, Repressor

    Keywords - Biological processi

    Apoptosis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homeobox protein SIX1
    Alternative name(s):
    Sine oculis homeobox homolog 1
    Gene namesi
    Name:Six1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:102780. Six1.

    Subcellular locationi

    Nucleus. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleolus Source: Ensembl
    3. nucleus Source: MGI
    4. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Perinatal lethality. Mice show failure in renal organogenesis, a severe reduction of most migratory hypaxial muscles including those of the forelimb, diaphragm and tongue, and severe rib-cage deformation. Besides, mice display craniofacial defects, including loss of inner ear structures. Pax2, Six2 and Sall1 expression is markedly reduced in the metanephric mesenchyme at E10.5 during kidney development. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland.5 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 284284Homeobox protein SIX1PRO_0000049296Add
    BLAST

    Post-translational modificationi

    Phosphorylated during interphase; becomes hyperphosphorylated during mitosis. Hyperphosphorylation impairs binding to promoter elements By similarity.By similarity
    Ubiquitinated by the anaphase promoting complex (APC), leading to its proteasomal degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ62231.

    PTM databases

    PhosphoSiteiQ62231.

    Expressioni

    Tissue specificityi

    Expressed in phalangeal tendons and in skeletal muscle and in head and body mesenchyme.

    Developmental stagei

    First expressed at E8.2-8.5 of embryo development in the anterior head mesoderm and developing pharyngeal pouches. Expression in the developing limb begins at E11 and is more pronounced dorsally. It progresses into the developing phalanges at E13.5. In the developing inner ear detected in the otic placode and the surrounding surface ectoderm at E8.5. Expression became prominent at the invaginating otic pit and the nascent otic vesicle at E9.5. At E10.5, expression was limited to the ventral half of the otic vesicle. Subsequently, the expression became gradually restricted to the cochlear region at E11.5 and E12.5. At later stages detected exclusively in the cochlea at E14.5, and the expression in the cochlear duct persisted in the neonate. In the developing kidney, is expressed in the uninduced metanephric mesenchyme at E10.5 and in the induced mesenchyme around the ureteric bud at E11.5. At E17.5 to P0, expression becomes restricted to a subpopulation of collecting tubule epithelial cells.2 Publications

    Gene expression databases

    ArrayExpressiQ62231.
    BgeeiQ62231.
    GenevestigatoriQ62231.

    Interactioni

    Subunit structurei

    Interacts with EYA1. Interacts with CDC20 By similarity. Interacts with DACH1, EYA2 and EYA3.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Eya1P977673EBI-1368483,EBI-1368503

    Protein-protein interaction databases

    BioGridi203259. 10 interactions.
    IntActiQ62231. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62231.
    SMRiQ62231. Positions 1-185.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the SIX/Sine oculis homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG289502.
    GeneTreeiENSGT00540000070251.
    HOGENOMiHOG000261680.
    HOVERGENiHBG003609.
    InParanoidiQ62231.
    KOiK15614.
    OMAiPRQAPAM.
    OrthoDBiEOG7C5M8Z.
    PhylomeDBiQ62231.
    TreeFamiTF315545.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    [Graphical view]
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q62231-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL    50
    KAKAVVAFHR GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG 100
    RPLGAVGKYR VRRKFPLPRT IWDGEETSYC FKEKSRGVLR EWYAHNPYPS 150
    PREKRELAEA TGLTTTQVSN WFKNRRQRDR AAEAKERENT ENNNSSSNKQ 200
    NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQSNMGH ARSSNYSLPG 250
    LTASQPSHGL QAHQHQLQDS LLGPLTSSLV DLGS 284
    Length:284
    Mass (Da):32,210
    Last modified:April 13, 2004 - v2
    Checksum:i4A6F88000FB9F8EB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti12 – 143EQV → GQG in CAA56585. (PubMed:7720577)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X80339 mRNA. Translation: CAA56585.1.
    BC023304 mRNA. Translation: AAH23304.1.
    CCDSiCCDS25973.1.
    PIRiS60751.
    RefSeqiNP_033215.2. NM_009189.3.
    UniGeneiMm.4645.

    Genome annotation databases

    EnsembliENSMUST00000050029; ENSMUSP00000059026; ENSMUSG00000051367.
    GeneIDi20471.
    KEGGimmu:20471.
    UCSCiuc007nwa.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X80339 mRNA. Translation: CAA56585.1 .
    BC023304 mRNA. Translation: AAH23304.1 .
    CCDSi CCDS25973.1.
    PIRi S60751.
    RefSeqi NP_033215.2. NM_009189.3.
    UniGenei Mm.4645.

    3D structure databases

    ProteinModelPortali Q62231.
    SMRi Q62231. Positions 1-185.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203259. 10 interactions.
    IntActi Q62231. 1 interaction.

    PTM databases

    PhosphoSitei Q62231.

    Proteomic databases

    PRIDEi Q62231.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000050029 ; ENSMUSP00000059026 ; ENSMUSG00000051367 .
    GeneIDi 20471.
    KEGGi mmu:20471.
    UCSCi uc007nwa.2. mouse.

    Organism-specific databases

    CTDi 6495.
    MGIi MGI:102780. Six1.

    Phylogenomic databases

    eggNOGi NOG289502.
    GeneTreei ENSGT00540000070251.
    HOGENOMi HOG000261680.
    HOVERGENi HBG003609.
    InParanoidi Q62231.
    KOi K15614.
    OMAi PRQAPAM.
    OrthoDBi EOG7C5M8Z.
    PhylomeDBi Q62231.
    TreeFami TF315545.

    Miscellaneous databases

    NextBioi 298579.
    PROi Q62231.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q62231.
    Bgeei Q62231.
    Genevestigatori Q62231.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    [Graphical view ]
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Homeobox genes and connective tissue patterning."
      Oliver G., Wehr R., Jenkins N.A., Copeland N.G., Cheyette B.N.R., Hartenstein V., Zipursky S.L., Gruss P.
      Development 121:693-705(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-284.
      Strain: C57BL/6J.
      Tissue: Embryo.
    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: Salivary gland.
    3. "Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1."
      Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K.
      Hum. Mol. Genet. 11:1045-1058(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH EYA2.
    4. "Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site."
      Spitz F., Demignon J., Porteu A., Kahn A., Concordet J.P., Daegelen D., Maire P.
      Proc. Natl. Acad. Sci. U.S.A. 95:14220-14225(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: DNA-BINDING.
    5. "Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein."
      Ikeda K., Watanabe Y., Ohto H., Kawakami K.
      Mol. Cell. Biol. 22:6759-6766(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH EYA3.
    6. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    7. "Six1 is required for the early organogenesis of mammalian kidney."
      Xu P.X., Zheng W., Huang L., Maire P., Laclef C., Silvius D.
      Development 130:3085-3094(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
    8. "Thymus, kidney and craniofacial abnormalities in Six 1 deficient mice."
      Laclef C., Souil E., Demignon J., Maire P.
      Mech. Dev. 120:669-679(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    9. "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis."
      Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.
      Nature 426:247-254(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH DACH1 AND EYA3.
    10. Cited for: FUNCTION, DEVELOPMENTAL STAGE.
    11. "The homeoprotein six1 transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis."
      Yu Y., Davicioni E., Triche T.J., Merlino G.
      Cancer Res. 66:1982-1989(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1 and Six4 gene expression."
      Richard A.F., Demignon J., Sakakibara I., Pujol J., Favier M., Strochlic L., Le Grand F., Sgarioto N., Guernec A., Schmitt A., Cagnard N., Huang R., Legay C., Guillet-Deniau I., Maire P.
      Dev. Biol. 359:303-320(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiSIX1_MOUSE
    AccessioniPrimary (citable) accession number: Q62231
    Secondary accession number(s): Q8CIL7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: April 13, 2004
    Last modified: October 1, 2014
    This is version 127 of the entry and version 2 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