SIX1

The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul 2008]

SIX Homeobox 1

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 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:27923061, PubMed:23435380, PubMed:15141091, PubMed:19497856).
Regulates the expression of numerous genes, including MYC, CCND1 and EZR (By similarity).
Acts as 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).

Biological Process aorta morphogenesisIEA:Ensembl
Biological Process apoptotic processIEA:UniProtKB-KW
Biological Process branching involved in ureteric bud morphogenesisISS:UniProtKB
Biological Process cellular response to 3,3',5-triiodo-L-thyronineIEA:Ensembl
Biological Process cochlea morphogenesisIEA:Ensembl
Biological Process embryonic cranial skeleton morphogenesisISS:UniProtKB
Biological Process embryonic skeletal system morphogenesisISS:UniProtKB
Biological Process endothelin receptor signaling pathwayIEA:Ensembl
Biological Process epithelial cell differentiationISS:UniProtKB
Biological Process facial nerve morphogenesisIEA:Ensembl
Biological Process fungiform papilla morphogenesisIEA:Ensembl
Biological Process generation of neuronsISS:UniProtKB
Biological Process inner ear developmentISS:UniProtKB
Biological Process inner ear morphogenesisISS:UniProtKB
Biological Process kidney developmentISS:UniProtKB
Biological Process mesenchymal cell proliferation involved in ureter developmentIEA:Ensembl
Biological Process mesonephric tubule formationISS:UniProtKB
Biological Process metanephric mesenchyme developmentISS:UniProtKB
Biological Process middle ear morphogenesisIEA:Ensembl
Biological Process myoblast migrationISS:UniProtKB
Biological Process myoblast proliferationIEA:Ensembl
Biological Process myotome developmentIEA:Ensembl
Biological Process negative regulation of neuron apoptotic processISS:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Biological Process neural crest cell differentiationIEA:Ensembl
Biological Process neuron fate specificationIEA:Ensembl
Biological Process Notch signaling pathwayIEA:Ensembl
Biological Process olfactory placode formationIEA:Ensembl
Biological Process organ inductionISS:UniProtKB
Biological Process otic vesicle developmentIEA:Ensembl
Biological Process outflow tract morphogenesisIEA:Ensembl
Biological Process pattern specification processISS:UniProtKB
Biological Process pharyngeal system developmentIEA:Ensembl
Biological Process positive regulation of branching involved in ureteric bud morphogenesisISS:UniProtKB
Biological Process positive regulation of brown fat cell differentiationISS:UniProtKB
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of mesenchymal cell proliferation involved in ureter developmentIEA:Ensembl
Biological Process positive regulation of myoblast proliferationIEA:Ensembl
Biological Process positive regulation of secondary heart field cardioblast proliferationIEA:Ensembl
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of ureteric bud formationISS:UniProtKB
Biological Process protein localization to nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of branch elongation involved in ureteric bud branchingISS:UniProtKB
Biological Process regulation of DNA-templated transcriptionISS:UniProtKB
Biological Process regulation of epithelial cell proliferationIEA:Ensembl
Biological Process regulation of neuron differentiationISS:UniProtKB
Biological Process regulation of protein localizationIEA:Ensembl
Biological Process regulation of skeletal muscle cell differentiationIEA:Ensembl
Biological Process regulation of skeletal muscle cell proliferationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of skeletal muscle satellite cell proliferationIEA:Ensembl
Biological Process regulation of synaptic assembly at neuromuscular junctionIEA:Ensembl
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sensory perception of soundIEA:Ensembl
Biological Process skeletal muscle fiber developmentManual Assertion Based On ExperimentIBA:GO_Central
Biological Process skeletal muscle tissue developmentISS:UniProtKB
Biological Process thymus developmentISS:UniProtKB
Biological Process thyroid gland developmentISS:UniProtKB
Biological Process trigeminal ganglion developmentIEA:Ensembl
Biological Process ureter smooth muscle cell differentiationIEA:Ensembl
Biological Process ureteric bud developmentISS:UniProtKB

Nucleus
Cytoplasm

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.
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.

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.