InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SIX1

Summary

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.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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