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Function

Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (By similarity). Plays an important role in the development of several organs, including kidney, muscle and inner ear (By similarity). Depending on context, functions as a transcriptional repressor or activator (By similarity). Lacks an activation domain, and requires interaction with EYA family members for transcription activation (PubMed:15141091). Mediates nuclear translocation of EYA1 and EYA2 (PubMed:19497856). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer (PubMed:15141091, PubMed:19497856, PubMed:23435380, PubMed:27923061). Regulates the expression of numerous genes, including MYC, CCND1 and EZR (By similarity). Acts as an activator of the IGFBP5 promoter, probably coactivated by EYA2 (By similarity). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (By similarity). During myogenesis, seems to act together with EYA2 and DACH2 (By similarity). Regulates the expression of CCNA1 (PubMed:15123840). Promotes brown adipocyte differentiation (By similarity).

Involvement in disease

Deafness, autosomal dominant, 23

DFNA23

A form of non-syndromic deafness characterized by prelingual, bilateral, symmetric hearing loss with a conductive component present in some but not all patients.

None

The disease is caused by variants affecting the gene represented in this entry.

Branchiootic syndrome 3

BOS3

A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients.

None

The disease is caused by variants affecting the gene represented in this entry.

Defects in SIX1 could be a cause of branchiootorenal syndrome (BOR). BOR is an autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to mondini type cochlear defect and stapes fixation. Penetrance of BOR syndrome is high, although expressivity can be extremely variable.

Post-translational modifications

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

Ubiquitinated by the anaphase promoting complex (APC), leading to its proteasomal degradation.

Sequence similarities

Belongs to the SIX/Sine oculis homeobox family.

Tissue specificity

Specifically expressed in skeletal muscle.

Cellular localization

  • Nucleus
  • Cytoplasm

Alternative names

Homeobox protein SIX1, Sine oculis homeobox homolog 1, SIX1

Target type

Proteins

Primary research area

Oncology

Molecular weight

32210Da

We found 1 product in 1 category

Proteins & Peptides

Target

Species of origin

Search our catalogue for 'SIX1' (1)

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