Sex-determining region Y protein

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Sex-determining Region Y Protein[edit | edit source]

Location of the SRY gene on the Y chromosome

The Sex-determining Region Y protein (SRY protein) is a critical transcription factor involved in the initiation of male sex determination in humans. It is encoded by the SRY gene, which is located on the Y chromosome. The presence of the SRY protein triggers the development of male physical characteristics by promoting the formation of testes from the undifferentiated gonadal tissue.

Structure[edit | edit source]

The SRY protein is a member of the high-mobility group (HMG) of transcription factors. It contains a conserved DNA-binding domain known as the HMG box, which allows it to bind to specific DNA sequences and bend the DNA, facilitating the transcription of target genes. The HMG box is crucial for the protein's function in sex determination.

Function[edit | edit source]

The primary role of the SRY protein is to initiate the development of the testes from the bipotential gonadal ridge in the embryo. It does this by upregulating the expression of SOX9, another transcription factor that is essential for testis development. The activation of SOX9 leads to the differentiation of Sertoli cells, which are necessary for the formation of testicular cords and the subsequent development of male reproductive structures.

Mechanism of Action[edit | edit source]

The SRY protein binds to specific DNA sequences in the promoters of target genes, causing a conformational change in the DNA that facilitates the recruitment of other transcription factors and the transcriptional machinery. This process initiates a cascade of gene expression changes that result in the development of male characteristics.

Clinical Significance[edit | edit source]

Mutations in the SRY gene can lead to disorders of sex development (DSDs). For example, a mutation that disrupts the function of the SRY protein can result in Swyer syndrome, where an individual with an XY karyotype develops as a female due to the failure of testis development. Conversely, translocation of the SRY gene to an X chromosome can cause XX individuals to develop male characteristics.

Evolution[edit | edit source]

The SRY gene is believed to have evolved from a gene duplication event of the SOX3 gene, which is located on the X chromosome. The acquisition of the SRY gene on the Y chromosome was a pivotal event in the evolution of mammalian sex determination.

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Contributors: Prab R. Tumpati, MD