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Aliases for SIX1 Gene

Aliases for SIX1 Gene

  • SIX Homeobox 1 2 3
  • Sine Oculis Homeobox Homolog 1 3 4
  • DFNA23 3 6
  • BOS3 3 6
  • Sine Oculis Homeobox (Drosophila) Homolog 1 2
  • Sine Oculis Homeobox Homolog 1 (Drosophila) 2
  • Deafness, Autosomal Dominant 23 2
  • Homeobox Protein SIX1 3
  • TIP39 3

External Ids for SIX1 Gene

Previous HGNC Symbols for SIX1 Gene

  • DFNA23

Previous GeneCards Identifiers for SIX1 Gene

  • GC14M058438
  • GC14M054906
  • GC14M059102
  • GC14M060182
  • GC14M061111
  • GC14M041274
  • GC14M061113

Summaries for SIX1 Gene

Entrez Gene Summary for SIX1 Gene

  • 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]

GeneCards Summary for SIX1 Gene

SIX1 (SIX Homeobox 1) is a Protein Coding gene. Diseases associated with SIX1 include deafness, autosomal dominant 23 and brachiootic syndrome 3. Among its related pathways are Transcriptional misregulation in cancer. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and chromatin binding. An important paralog of this gene is SIX6.

UniProtKB/Swiss-Prot for SIX1 Gene

  • 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.

Gene Wiki entry for SIX1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIX1 Gene

Genomics for SIX1 Gene

Regulatory Elements for SIX1 Gene

Genomic Location for SIX1 Gene

Start:
60,643,415 bp from pter
End:
60,658,259 bp from pter
Size:
14,845 bases
Orientation:
Minus strand

Genomic View for SIX1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SIX1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIX1 Gene

Proteins for SIX1 Gene

  • Protein details for SIX1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15475-SIX1_HUMAN
    Recommended name:
    Homeobox protein SIX1
    Protein Accession:
    Q15475
    Secondary Accessions:
    • Q53Y16
    • Q96H64

    Protein attributes for SIX1 Gene

    Size:
    284 amino acids
    Molecular mass:
    32210 Da
    Quaternary structure:
    • Interacts with DACH1 and EYA3 (By similarity). Interacts with EYA1 and EYA2. Interacts with CDC20.

    Three dimensional structures from OCA and Proteopedia for SIX1 Gene

neXtProt entry for SIX1 Gene

Proteomics data for SIX1 Gene at MOPED

Post-translational modifications for SIX1 Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIX1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SIX1 Gene

Domains for SIX1 Gene

Gene Families for SIX1 Gene

HGNC:
  • SIX :Homeoboxes / SINE class

Suggested Antigen Peptide Sequences for SIX1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q15475

UniProtKB/Swiss-Prot:

SIX1_HUMAN :
  • Q15475
Domain:
  • Contains 1 homeobox DNA-binding domain.
Family:
  • Belongs to the SIX/Sine oculis homeobox family.
genes like me logo Genes that share domains with SIX1: view

Function for SIX1 Gene

Molecular function for SIX1 Gene

GENATLAS Biochemistry: Drosophila sine oculis homolog SIX1 homeo box encoding gene,expressed during development in limb tendons,also expressed in skeletal and smooth muscle
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for SIX1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IMP 15141091
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IMP 15141091
GO:0003677 DNA binding IDA 19497856
GO:0003682 chromatin binding IEA --
GO:0003700 sequence-specific DNA binding transcription factor activity ISS --
genes like me logo Genes that share ontologies with SIX1: view
genes like me logo Genes that share phenotypes with SIX1: view

Animal Models for SIX1 Gene

MGI Knock Outs for SIX1:

miRNA for SIX1 Gene

Targeting motifs for SIX1 Gene
HOMER Transcription Factor Regulatory Elements motif SIX1
  • Consensus sequence: GKVTCADRTTWC Submotif: canonical Cell Type: Myoblast GeoId: GSE20150

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targeting for SIX1 Gene

Localization for SIX1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIX1 Gene

Nucleus. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIX1 Gene COMPARTMENTS Subcellular localization image for SIX1 gene
Compartment Confidence
nucleus 5
cytoskeleton 1
extracellular 1

Gene Ontology (GO) - Cellular Components for SIX1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005667 transcription factor complex ISS --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with SIX1: view

Pathways for SIX1 Gene

genes like me logo Genes that share pathways with SIX1: view

Pathways by source for SIX1 Gene

1 KEGG pathway for SIX1 Gene

Gene Ontology (GO) - Biological Process for SIX1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IEA --
GO:0001657 ureteric bud development ISS --
GO:0001658 branching involved in ureteric bud morphogenesis ISS --
GO:0001759 organ induction ISS --
GO:0001822 kidney development ISS --
genes like me logo Genes that share ontologies with SIX1: view

Transcripts for SIX1 Gene

mRNA/cDNA for SIX1 Gene

Unigene Clusters for SIX1 Gene

SIX homeobox 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIX1 Gene

No ASD Table

Relevant External Links for SIX1 Gene

GeneLoc Exon Structure for
SIX1
ECgene alternative splicing isoforms for
SIX1

Expression for SIX1 Gene

mRNA expression in normal human tissues for SIX1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SIX1 Gene

This gene is overexpressed in Muscle - Skeletal (20.7) and Pituitary (8.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SIX1 Gene

SOURCE GeneReport for Unigene cluster for SIX1 Gene Hs.633506

mRNA Expression by UniProt/SwissProt for SIX1 Gene

Q15475-SIX1_HUMAN
Tissue specificity: Specifically expressed in skeletal muscle
genes like me logo Genes that share expressions with SIX1: view

Orthologs for SIX1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIX1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIX1 35
  • 100 (n)
  • 100 (a)
SIX1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia -- 36
  • 5 (a)
OneToMany
SIX1 35
  • 93.19 (n)
  • 98.59 (a)
SIX1 36
  • 78 (a)
OneToMany
dog
(Canis familiaris)
Mammalia SIX1 35
  • 94.48 (n)
  • 99.65 (a)
SIX1 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Six1 35
  • 93.31 (n)
  • 99.3 (a)
Six1 16
Six1 36
  • 99 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIX1 36
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SIX1 36
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Six1 35
  • 93.19 (n)
  • 99.3 (a)
chicken
(Gallus gallus)
Aves SIX1 35
  • 85.22 (n)
  • 92.55 (a)
SIX1 36
  • 92 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIX1 36
  • 87 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Six1 35
tropical clawed frog
(Silurana tropicalis)
Amphibia six1 35
  • 78.4 (n)
  • 94.37 (a)
Str.9229 35
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.722 35
zebrafish
(Danio rerio)
Actinopterygii Dr.27681 35
six1b 35
  • 77.46 (n)
  • 91.9 (a)
six1b 36
  • 92 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011695 35
  • 74.29 (n)
  • 87.23 (a)
fruit fly
(Drosophila melanogaster)
Insecta so 35
  • 76.32 (n)
  • 87.43 (a)
so 36
  • 43 (a)
OneToMany
so 37
  • 87 (a)
Six4 37
  • 62 (a)
worm
(Caenorhabditis elegans)
Secernentea ceh-33 36
  • 44 (a)
OneToMany
ceh-33 37
  • 61 (a)
ceh-32 37
  • 56 (a)
ceh-35 37
  • 38 (a)
ceh-34 37
  • 53 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.7135 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 24 (a)
ManyToMany
Species with no ortholog for SIX1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIX1 Gene

ENSEMBL:
Gene Tree for SIX1 (if available)
TreeFam:
Gene Tree for SIX1 (if available)

Paralogs for SIX1 Gene

Paralogs for SIX1 Gene

Selected SIMAP similar genes for SIX1 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with SIX1: view

Variants for SIX1 Gene

Sequence variations from dbSNP and Humsavar for SIX1 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type MAF
rs3742637 -- 60,645,239(-) TGAGT(G/T)GTGTA utr-variant-3-prime
rs3742638 -- 60,645,163(-) GAATT(A/G)CAGGG utr-variant-3-prime
rs3832952 -- 60,645,012(-) TTCAT(-/AT)GTTAA utr-variant-3-prime
rs3841301 -- 60,650,508(+) AATAT(-/AAT)CCTTA upstream-variant-2KB
rs4627254 -- 60,649,982(+) GCTTA(A/T)GGAAC upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for SIX1 Gene

Variant ID Type Subtype PubMed ID
nsv819505 CNV Gain 19587683
nsv1295 CNV Loss 18451855

Relevant External Links for SIX1 Gene

HapMap Linkage Disequilibrium report
SIX1
Human Gene Mutation Database (HGMD)
SIX1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIX1 Gene

Disorders for SIX1 Gene

(2) OMIM Diseases for SIX1 Gene (601205)

UniProtKB/Swiss-Prot

SIX1_HUMAN
  • 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:0000269 PubMed: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:0000269 PubMed:15141091, ECO:0000269 PubMed:17637804, ECO:0000269 PubMed:18330911, ECO:0000269 PubMed: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.

(3) University of Copenhagen DISEASES for SIX1 Gene

(10) Novoseek inferred disease relationships for SIX1 Gene

Disease -log(P) Hits PubMed IDs
bor syndrome 97.1 16
renal anomaly 87.9 1
urinary tract anomaly 73.2 2
rhabdomyosarcoma 35.1 1
metastasis 25.4 9

Relevant External Links for SIX1

GeneTests
SIX1
GeneReviews
SIX1
Human Genome Epidemiology (HuGE) Navigator
SIX1
genes like me logo Genes that share disorders with SIX1: view

Publications for SIX1 Gene

  1. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. (PMID: 15141091) Ruf R.G. … Hildebrandt F. (Proc. Natl. Acad. Sci. U.S.A. 2004) 2 3 4 23
  2. Cell cycle regulation of the human Six1 homeoprotein is mediated by APC(Cdh1). (PMID: 17130831) Christensen K.L. … Ford H.L. (Oncogene 2007) 3 4 23
  3. Branchio-oto-renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses. (PMID: 17637804) Sanggaard K.M. … Tranebjaerg L. (Eur. J. Hum. Genet. 2007) 3 4 23
  4. SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR. (PMID: 18330911) Kochhar A. … Smith R.J. (Hum. Mutat. 2008) 3 4 23
  5. Biochemical and functional characterization of six SIX1 Branchio-oto- renal syndrome mutations. (PMID: 19497856) Patrick A.N. … Ford H.L. (J. Biol. Chem. 2009) 3 4 23

Products for SIX1 Gene

Sources for SIX1 Gene

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