Biomarker: SIX1

Histology type: endometrial carcinoma

Country: USA

Region: North Carolina

Followed up time :

Conclusion: The SIX1 oncoprotein is aberrantly expressed in the endometrium following developmental exposure to estrogenic chemicals, correlates with uterine cancer, and is a biomarker in human endometrial cancers.

Sample type : tissue

Sample method: immunohistochemistry,Real time RT-PCR

Expression pattern : aberrantly expressed

Expression elevation: Overall abundance of SIX1 immunolabeling was evaluated by light microscopy and assigned a qualitative labeling score from 0–4 (0=absent, 1=minimal, 2=mild, 3=moderate, 4=severe) based on staining intensity and the estimated percentage of labeled cells within a section.

Funtion Uniprot: Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (By similarity). Plays an important role in the development of several organs, including kidney, muscle and inner ear (By similarity). Depending on context, functions as transcriptional repressor or activator (By similarity). Lacks an activation domain, and requires interaction with EYA family members for transcription activation (PubMed:15141091). Mediates nuclear translocation of EYA1 and EYA2 (PubMed:19497856). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer (PubMed:27923061, PubMed:23435380, PubMed:15141091, PubMed:19497856). Regulates the expression of numerous genes, including MYC, CCND1 and EZR (By similarity). Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2 (By similarity). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (By similarity). During myogenesis, seems to act together with EYA2 and DACH2 (By similarity). Regulates the expression of CCNA1 (PubMed:15123840). Promotes brown adipocyte differentiation (By similarity).

UniProt ID: Q15475

UniProt Link: https://www.uniprot.org/uniprotkb/Q15475/entry

Biological function from UniProt: Apoptosis, Transcription, Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Specifically expressed in skeletal muscle.

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Recommended name: Homeobox protein SIX1

Gene name from HGNC: 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]

HPA class: Cancer-related genes Disease related genes Human disease related genes Transcription factors

AlphaFold DB: Q15475

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q15475

HPA link: https://www.proteinatlas.org/ENSG00000126778-SIX1

Tissue specificity RNA from HPA: Tissue enhanced (parathyroid gland, salivary gland, skeletal muscle, tongue)

Tissue expression from HPA: Nuclear expression in selected tissues.

Single cell type specificity Cell type enhanced (Skeletal myocytes, Respiratory ciliated cells, Club cells, Basal respiratory cells, Basal prostatic cells, Ionocytes, Prostatic glandular cells, Spermatogonia)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Nucleoli (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in endometrial cancer (unfavorable) and lung cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000126778-SIX1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000126778-SIX1/pathology/endometrial+cancer

Expression figure legend: SIX1 immunolabeling in human endometrial cancers.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025359/figure/F3/

Phenotype ID: 605192;608389;

Disease: Deafness, autosomal dominant, 23 (DFNA23);Branchiootic syndrome 3 (BOS3);No disease ID;

Note1: The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting the gene represented in this entry;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

OMIM: 601205

OMIM link1: https://www.omim.org/entry/605192;https://www.omim.org/entry/608389;

OMIM link2: https://www.omim.org/entry/601205

HGNC ID: HGNC:10887

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10887