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Q62231

- SIX1_MOUSE

UniProt

Q62231 - SIX1_MOUSE

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Protein
Homeobox protein SIX1
Gene
Six1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 – 18360Homeobox1 Publication
Add
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 from RNA polymerase II promoter Source: MGI
  31. positive regulation of transcription, DNA-templated Source: UniProtKB
  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. ureter smooth muscle cell differentiation Source: MGI
  48. ureteric bud development Source: MGI
Complete GO annotation...

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
Complete GO annotation...

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 SIX1
PRO_0000049296Add
BLAST

Post-translational modificationi

Phosphorylated during interphase; becomes hyperphosphorylated during mitosis. Hyperphosphorylation impairs binding to promoter elements 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 EYA3.3 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.

Family & Domainsi

Sequence similaritiesi

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 143EQV → GQG in CAA56585. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 126 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

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