SIX1 (sine oculis homeobox homolog 1) (mammalian)
2005-11-01 Heide L Ford , Aaron N Patrick , Marileila Varella-Garcia AffiliationDepts. of Obstetrics, Gynecology, Biochemistry, Molecular Genetics, University of Colorado Health Sciences Center, Fitzsimons Campus, Mail stop 8309, P.O. Box 6511, Aurora, CO 80045, USA
Identity
HGNC
LOCATION
14q23.1
LOCUSID
ALIAS
BOS3,DFNA23,TIP39
FUSION GENES
DNA/RNA
View of the SIX1 gene which is composed of 2 exons that are 833 and 543 bps respectively, and a single 2,052 bp intron. Start and stop codon positions are shown.
Description
The gene is composed of 2 exons and one intron and can be found on chromosome 14 at location 60,182,506-60,185,933.
Transcription
The transcript length is 1,376 base pairs and the start of the transcript is located in Contig AL049874.3.1.193047. The transcript can be detected in a variety of tissues during mouse development (see below for protein expression) and this has also been confirmed at the protein level (using reporter genes). The transcript is further detected throughout normal mouse mammary gland development with levels being the highest in the embryonic mammary gland and decreasing as the mammary gland differentiates in pregnancy and lactation. In the adult human, it is detected in skeletal muscle, pituitary gland, salivary gland, kidney, lung, and trachea.
Pseudogene
No
Proteins
View of the Six1 protein (total length 284 amino acids) that contains an N-terminal 115 amino acid Six domain (SD), and a 60 amino acid six-type homeodomain (HD). The SD is important for the interaction of Six1 with cofactors and also contributes to DNA binding along with the homeodomain.
Description
Six1 belongs to the Six family of homeoproteins. Amino acids: 284. Predicted Molecular Weight: 32210 Dalton. It exists as a phosphoprotein and is hyperphosphorylated in mitosis.
Expression
During mouse development, Six1 is expressed in otic vesicles, nasal placodes, branchial arches, Rathkes pouch, dorsal root ganglion, proximal cranial ganglia, somites, cranial mesenchyme, nephrogenic cords, and limb mesenchyme. Six1 expression in muscles is present throughout myogenesis and into adulthood.
Localisation
Nuclear
Function
Six1 is a transcription factor that is known to play a role in the proliferation and survival of precursor cells during normal development in numerous tissues including, amongst others, the kidney, inner ear, and muscle. It is also demonstrated to play a role in the proliferation of cancer cells and in cancer metastasis. It is known to activate several target genes, including cyclin A1, c-MYC, GDNF, and SLC12A2.
Mutations
Germinal
Germline mutations of SIX1 are observed in branchio-oto-renal sydrome, an autosomal dominant developmental disorder that is characterized by kidney and urinary tract malformations and hearing loss. The three SIX1 mutations identified to date all interfere with the ability of the Six1 protein to interact with its Eya1 cofactor, and two of the identified mutations additionally affect Six1-DNA binding.
Somatic
The SIX1 gene is amplified in about 5% of breast cancers (infiltrating ductal carcinomas). Overexpression of Six1 has been found in breast cancer, in Wilmstumors, and in rhabdomyosarcoma.
Implicated in
Entity name
Six1 is implicated in a number of cancers including breast cancer, rhabdomyosarcomas, and Wilms tumors. It has also been implicated in branchio-oto-renal syndrome.
Note
Six1 is overexpressed in approximately 50% of primary breast cancers and 90% of metastatic lesions. Its overexpression in breast cancer has been linked to increased proliferation of breast cancer cells. Six1 is also a critical mediator of metastasis in a mouse rhabdomyosarcoma model.
Disease
breast cancer, wilms tumor, rhabdomyosarcoma, branchio-oto-renal syndrome,
Cytogenetics
The SIX1 gene is amplified in human breast cancer
Idiogram of chromosome 14 (A) showing location of the SIX1 gene at 14q23 (clone RP11-1042B17, labeled in SpectrumRed). Clone RPMI-324B11 (labeled in SpectrumGreen) mapped at 14q11.2 was used as control. Metaphase spread (B) and interphase nuclei (C) of the non-malignant, immortalized MCF10A cell line showing two normal copies of chromosome 14 with signals generated by the SIX1 and control FISH probes. Metaphase spread of the mammary carcinoma cell line, 21MT2 (D), showing a normal copy of chromosome 14 with SIX1 (red) and control probe (green), two derivative chromosomes carrying only the SIX1 or the SIX1 and control signals and a copy of the derivative 14 chromosome with SIX1 gene amplification. Interphase nuclei from 21MT2 cells with multiple copies of red and green signals, including a cluster of SIX1 signals representing gene amplification (E).
Oncogenesis
SIX1 is overexpressed in several tumor types, including breast cancer, rhabdomyosarcomas, and Wilms tumors. It has been implicated in both the proliferation and metastasis of tumor cells.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|
Other Information
Locus ID:
NCBI: 6495
MIM: 601205
HGNC: 10887
Ensembl: ENSG00000126778
Variants:
dbSNP: 6495
ClinVar: 6495
TCGA: ENSG00000126778
COSMIC: SIX1
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000126778 | ENST00000554986 | H0YK85 |
| ENSG00000126778 | ENST00000645694 | Q15475 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Transcriptional misregulation in cancer | KEGG | ko05202 |
| Transcriptional misregulation in cancer | KEGG | hsa05202 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37779410 | 2024 | Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells. | 1 |
| 37779410 | 2024 | Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells. | 1 |
| 35017159 | 2023 | Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children. | 0 |
| 36892427 | 2023 | LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression. | 2 |
| 36937004 | 2023 | The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer. | 6 |
| 36961205 | 2023 | FOXC2-induced circCASK aggravates colorectal cancer progression by upregulating SIX1 expression. | 1 |
| 37479820 | 2023 | Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea. | 5 |
| 37551474 | 2023 | [Effect of Inhibiting SIX1 Expression on Drug-resistance of Acute Myeloid Leukemia Cell Line HL-60/ADR Cells]. | 0 |
| 37815464 | 2023 | Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor. | 1 |
| 38031089 | 2023 | SIX1 amplification modulates stemness and tumorigenesis in breast cancer. | 0 |
| 35017159 | 2023 | Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children. | 0 |
| 36892427 | 2023 | LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression. | 2 |
| 36937004 | 2023 | The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer. | 6 |
| 36961205 | 2023 | FOXC2-induced circCASK aggravates colorectal cancer progression by upregulating SIX1 expression. | 1 |
| 37479820 | 2023 | Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea. | 5 |
Citation
Heide L Ford ; Aaron N Patrick ; Marileila Varella-Garcia
SIX1 (sine oculis homeobox homolog 1) (mammalian)
Atlas Genet Cytogenet Oncol Haematol. 2005-11-01
Online version: http://atlasgeneticsoncology.org/gene/42302/six1
