Homo sapiens Protein: SIX1
InnateDB Protein IDBP-8304.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SIX1
Protein Name SIX homeobox 1
Synonyms BOS3; DFNA23; TIP39;
Species Homo sapiens
Ensembl Protein ENSP00000247182
InnateDB Gene IDBG-8302 (SIX1)
Protein Structure
UniProt Annotation
Function Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development. Plays an important role in the development of several organs, including kidney, muscle and inner ear. Depending on context, functions as transcriptional repressor or activator. Lacks an activation domain, and requires interaction with EYA family members for transcription activation. Mediates nuclear translocation of EYA1 and EYA2. Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter. Regulates the expression of numerous genes, including MYC, CCND1 and EZR. Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2. Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex. During myogenesis, seems to act together with EYA2 and DACH2 (By similarity). Regulates the expression of CCNA1. {ECO:0000250, ECO:0000269PubMed:15123840, ECO:0000269PubMed:15141091, ECO:0000269PubMed:19497856, ECO:0000269PubMed:23435380}.
Subcellular Localization Nucleus. Cytoplasm.
Disease Associations Deafness, autosomal dominant, 23 (DFNA23) [MIM:605192]: A form of non-syndromic deafness characterized by prelingual, bilateral, symmetric hearing loss with a conductive component present in some but not all patients. {ECO:0000269PubMed:15141091}. Note=The disease is caused by mutations affecting the gene represented in this entry.Branchiootic syndrome 3 (BOS3) [MIM:608389]: 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. {ECO:0000269PubMed:15141091, ECO:0000269PubMed:17637804, ECO:0000269PubMed:18330911, ECO:0000269PubMed:21280147}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=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.
Tissue Specificity Specifically expressed in skeletal muscle.
Number of Interactions This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.
Experimentally validated
Total 15 [view]
Protein-Protein 15 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 13 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001657 ureteric bud development
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001759 organ induction
GO:0001822 kidney development
GO:0003151 outflow tract morphogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006915 apoptotic process
GO:0007389 pattern specification process
GO:0007519 skeletal muscle tissue development
GO:0007605 sensory perception of sound
GO:0008582 regulation of synaptic growth at neuromuscular junction
GO:0010468 regulation of gene expression
GO:0021610 facial nerve morphogenesis
GO:0030855 epithelial cell differentiation
GO:0030878 thyroid gland development
GO:0032880 regulation of protein localization
GO:0034504 protein localization to nucleus
GO:0035909 aorta morphogenesis
GO:0042472 inner ear morphogenesis
GO:0042474 middle ear morphogenesis
GO:0043524 negative regulation of neuron apoptotic process
GO:0045664 regulation of neuron differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048538 thymus development
GO:0048665 neuron fate specification
GO:0048699 generation of neurons
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0048704 embryonic skeletal system morphogenesis
GO:0048705 skeletal system morphogenesis
GO:0048839 inner ear development
GO:0048856 anatomical structure development
GO:0051451 myoblast migration
GO:0060037 pharyngeal system development
GO:0071599 otic vesicle development
GO:0072001 renal system development
GO:0072075 metanephric mesenchyme development
GO:0072095 regulation of branch elongation involved in ureteric bud branching
GO:0072107 positive regulation of ureteric bud formation
GO:0072172 mesonephric tubule formation
GO:0072193 ureter smooth muscle cell differentiation
GO:0072513 positive regulation of secondary heart field cardioblast proliferation
GO:0090103 cochlea morphogenesis
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis
GO:0090191 negative regulation of branching involved in ureteric bud morphogenesis
GO:2000729 positive regulation of mesenchymal cell proliferation involved in ureter development
Cellular Component
GO:0005634 nucleus
GO:0005667 transcription factor complex
GO:0005730 nucleolus
GO:0005737 cytoplasm
Protein Structure and Domains
InterPro IPR001356 Homeobox domain
IPR009057 Homeodomain-like
PFAM PF00046
Post-translational Modifications
SwissProt Q15475
PhosphoSite PhosphoSite-Q15475
UniProt Splice Variant
Entrez Gene 6495
UniGene Hs.734092
RefSeq NP_005973
OMIM 601205
HPRD 03125
EMBL AF323497 BC008874 BT007083 X91868
GenPept AAH08874 AAK06772 AAP35746 CAA62974