SIX3 - Homeobox protein SIX3 - human protein (Function)
 
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SIX3 »  Homeobox protein SIX3
 
Protein also known as:  Sine oculis homeobox homolog 3.
Gene name:  SIX3
Entry whose protein(s) existence is based on evidence at protein level
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1 33 1
GENE REF ISO

Function

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Overview 
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 AES 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 functions also 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 (By similarity). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway.  
3
  • UniProtKB
GO molecular function 
Protein bindingdefinition[GO:0005515]  
1
  • UniProtKB
RNA polymerase II distal enhancer sequence-specific DNA bindingdefinition[GO:0000980] silver  
1
  • Ortholog Compara
RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptiondefinition[GO:0001205] silver  
1
  • Ortholog Compara
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
1
  • Ortholog Curator
Transcription coactivator activitydefinition[GO:0003713]  
1
  • Ortholog Curator
Transcription corepressor bindingdefinition[GO:0001222]  
1
  • UniProtKB
GO biological process 
Apoptotic process involved in developmentdefinition[GO:1902742]  
1
  • Ortholog Curator
Brain developmentdefinition[GO:0007420]  
1
  • PINC
Cell proliferation in forebraindefinition[GO:0021846]  
1
  • Ortholog Curator
Circadian behaviordefinition[GO:0048512] silver  
1
  • Ortholog Compara
Epithelial cell maturationdefinition[GO:0002070]  
1
  • Ortholog Curator
Eye developmentdefinition[GO:0001654]  
1
  • UniProtKB
Forebrain anterior/posterior pattern specificationdefinition[GO:0021797] silver  
1
  • Ortholog Compara
Forebrain dorsal/ventral pattern formationdefinition[GO:0021798]  
1
  • UniProtKB
Lens development in camera-type eyedefinition[GO:0002088]  
1
  • Ortholog Curator
Lens fiber cell apoptotic processdefinition[GO:1990086]  
1
  • Ortholog Curator
Lens fiber cell differentiationdefinition[GO:0070306]  
1
  • Ortholog Curator
Lens induction in camera-type eyedefinition[GO:0060235] silver  
1
  • Ortholog Compara
Negative regulation of neuron differentiationdefinition[GO:0045665]  
1
  • Ortholog Curator
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
1
  • UniProtKB
Negative regulation of Wnt signaling pathwaydefinition[GO:0030178] silver  
1
  • Ortholog Compara
Neuroblast differentiationdefinition[GO:0014016]  
1
  • Ortholog Curator
Neuroblast migrationdefinition[GO:0097402]  
1
  • Ortholog Curator
Optic vesicle morphogenesisdefinition[GO:0003404]  
1
  • Ortholog Curator
Pituitary gland developmentdefinition[GO:0021983]  
1
  • Ortholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
1
  • Ortholog Compara
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • Ortholog Curator
Proximal/distal axis specificationdefinition[GO:0009946]  
1
  • Ortholog Curator
Regulation of cell cycle phase transitiondefinition[GO:1901987]  
1
  • Ortholog Curator
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • Ortholog Curator
Regulation of neural precursor cell proliferationdefinition[GO:2000177]  
1
  • Ortholog Curator
Regulation of neural retina developmentdefinition[GO:0061074]  
1
  • Ortholog Curator
Regulation of neuroblast proliferationdefinition[GO:1902692]  
1
  • Ortholog Curator
Telencephalon developmentdefinition[GO:0021537]  
1
  • Ortholog Curator
Telencephalon regionalizationdefinition[GO:0021978]  
1
  • Ortholog Curator
Transcription from RNA polymerase II promoterdefinition[GO:0006366] silver  
1
  • Ortholog Compara
Visual perceptiondefinition[GO:0007601]  
1
  • PINC
 

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Developmental protein  definition   [KW-0217]
Repressor  definition   [KW-0678]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: SIX3
GenomeRNAi: 6496
PRO: PR:O95343