InnateDB Protein
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IDBP-8304.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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SIX1
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Protein Name
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SIX homeobox 1
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Synonyms
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BOS3; DFNA23; TIP39;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000247182
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InnateDB Gene
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IDBG-8302 (SIX1)
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Protein Structure
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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}.
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Subcellular Localization |
Nucleus. Cytoplasm.
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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.
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Tissue Specificity |
Specifically expressed in skeletal muscle.
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Comments |
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Number of Interactions
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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]
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Protein-Protein |
15
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
13 [view]
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
IPR001356
Homeobox domain
IPR009057
Homeodomain-like
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PFAM |
PF00046
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PRINTS |
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PIRSF |
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SMART |
SM00389
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TIGRFAMs |
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Modification |
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SwissProt |
Q15475
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PhosphoSite |
PhosphoSite-Q15475
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
6495
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UniGene |
Hs.734092
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RefSeq |
NP_005973
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HUGO |
HGNC:10887
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OMIM |
601205
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CCDS |
CCDS9748
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HPRD |
03125
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IMGT |
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EMBL |
AF323497
BC008874
BT007083
X91868
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GenPept |
AAH08874
AAK06772
AAP35746
CAA62974
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