Homeobox protein SIX3

UniProt Q62233 Organism Mus musculus Gene Six3

Also known as: Six3

Function

Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is TLE5 and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 also functions in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway. Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway (By similarity).

Classification

Family (Pfam): PF00046 Homeodomain, PF16878 SIX1_SD
InterPro: HD, Homeodomain-like_sf, SIX1_SD
Functional cluster: Homeobox & Zinc-Finger Transcription Factors

Gene Ontology · 47

Neighborhood · nearest proteins

Nearest neighbours of Homeobox protein SIX3: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Homeobox protein SIX3 2 shared papers
Protein phosphatase EYA4 1 shared papers
Homeobox protein SIX3 1 shared papers
Protein phosphatase EYA1 1 shared papers
Homeobox protein SIX5 1 shared papers
Homeobox protein SIX2 1 shared papers
Metastasis-associated protein MTA1 2 shared papers
Homeobox protein SIX6 1 shared papers
TLE family member 5 1 shared papers
Metastasis-associated protein MTA1 1 shared papers
Histone deacetylase 2 1 shared papers
Transducin-like enhancer protein 4 1 shared papers

Literature · 21 cited papers

Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain. Dev. Biol. · 2013
Six3 is required for ependymal cell maturation. Development · 2011
Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. J. Clin. Invest. · 2010
Metastasis-associated protein 1 and its short form variant stimulates Wnt1 transcription through promoting its derepression from Six3 corepressor. Cancer Res. · 2010
EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Hum. Mutat. · 2009
Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev. Biol. · 2008
Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. Dev. Cell · 2008
Six3 inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon. Development · 2008
Repression of Six3 by a corepressor regulates rhodopsin expression. Proc. Natl. Acad. Sci. U.S.A. · 2007
Six3 controls the neural progenitor status in the murine CNS. Cereb. Cortex · 2008
Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. EMBO J. · 2006
Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction. Gene Expr. Patterns · 2005
… and 9 more in the literature graph

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