Tbio SIX3 Homeobox protein SIX3

Protein Summary

Description

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. This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• O95343
• D6W5A5
• Q53T42

Gene Name

• SIX3

Ensembl ID

• ENST00000260653
• ENSP00000260653
• ENSG00000138083

Symbol

• HPE2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.98
molecular function	0.95
PubMedID	0.68
microRNA	0.62
co-expressed gene	0.61

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Helix-turn-helix Transcription Factor / Homeodomain Transcription Factor / Homeobox Protein Six3

DTO Classes

Protein / Transcription Factor / Helix-turn-helix Transcription Factor / Homeodomain Transcription Factor / Homeobox Protein Six3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 197.58   (req: < 5)

Gene RIFs: 31   (req: <= 3)

Antibodies: 239   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 197.58   (req: >= 5)

Gene RIFs: 31   (req: > 3)

Antibodies: 239   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0