TOX high mobility group box family member 3, also known as ''TOX3'', is a human

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

encoded by this gene is a member of a subfamily of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s that also includes ''

TOX Tox or TOX may refer to: Science and technology * TOX, a protein encoded by the TOX gene * Tox screen, medical diagnostic screening for toxic substances Computing * Tox (protocol), peer-to-peer instant messaging software * tox (Python testing ...

'', ''

TOX2 TOX high mobility group box family member 2, also known as TOX2, is a human gene. The protein encoded by this gene is a member of a subfamily of transcription factors that also includes TOX, TOX3, and TOX4 that share almost identical HMG-box DNA- ...

'', and ''

TOX4 TOX4 (TOX high mobility group box family member 4) also known as KIAA0737, is a human gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation' ...

'' that share almost identical

HMG-box In molecular biology, the HMG-box (high mobility group box) is a protein domain which is involved in DNA binding. Structure The structure of the HMG-box domain contains three alpha helices separated by loops (see figure to the right). Function ...

DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...

s which function to modify

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

structure by unwinding and bending DNA. The protein TOX3 has a glutamine-rich C-terminus due to CAG repeats. ''TOX3'' is located on human chromosome band 16q12.1. The gene consists of seven exons and is highly expressed in both the brain and luminal epithelial breast tissue. Mutations in the gene are associated with increased susceptibility to breast cancer. ''TOX3'' plays a role in regulating calcium-dependent transcription and interacts with cAMP-response-element-binding protein (

CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...

) and CREB-binding protein (

CBP CBP may refer to: Business parks * Cebu Business Park, a central business district in Cebu City, Philippines * Changi Business Park, an eco-friendly industrial park in Singapore * Chiswick Business Park, a business park in Gunnersbury, West London ...

). It also increases transcription via interaction with

CITED1 Cbp/p300-interacting transactivator 1 is a protein that in humans is encoded by the ''CITED1'' gene. Interactions CITED1 has been shown to interact with HSPA8 Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc7 ...

, a transcription co-regulator that increases transcription factor activity.

Disease linkage

Mutations in the ''TOX3'' gene are associated with an increased risk of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

. The risk allele rs3803662 is a low-penetrance SNP (single nucleotide polymorphism) associated with decreased expression of ''TOX3'' and an increase in breast cancer risk. The risk locus was reported to regulate affinity of ''

FOXA1 Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the ''FOXA1'' gene. Function FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte ...

'' binding to chromatin, potentially affecting ''TOX3'' expression. This locus also interacts with high-penetrance mutations ''

BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...

'' and ''

BRCA2 ''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...

'' to increase risk. The rs3803662 variant has a high frequency in the population, with a minor allele frequency of 0.25. Little is known of the transcriptional mechanisms and protein interactions of ''TOX3''. However, a 2019 publication identified ''TOX3'' as a cancer suppressor gene in

clear cell renal cell carcinoma Clear-cell renal-cell carcinoma (CCRCC) is a type of renal-cell carcinoma. Genetics Cytogenetics * Alterations of chromosome 3p segments occurs in 70–90% of CCRCCs * Inactivation of von Hippel–Lindau disease ( VHL) gene by gene mutation a ...

(ccRCC) and reported that downregulation of ''TOX3'' facilitates the

epithelial mesenchymal transition Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

by decreasing repression of ''

SNAI1 Zinc finger protein SNAI1 (sometimes referred to as Snail) is a protein that in humans is encoded by the ''SNAI1'' gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithel ...

'' and ''

SNAI2 Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the ''SNAI2'' gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation. Function This gene encodes a member ...

'', resulting in tumor growth and metastasis. Like breast cancer, downregulation of ''TOX3'' is associated with worse prognosis in ccRCC patients.

References

Transcription factors {{gene-20-stub