Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the GJB2 gene.

Function

Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels. Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are designated by their molecular mass. Another system of nomenclature divides gap junction proteins into two categories, alpha and beta, according to sequence similarities at the nucleotide and amino acid levels. For example, CX43 (GJA1) is designated alpha-1 gap junction protein, whereas GJB1 (CX32), and GJB2 (CX26; this protein) are called beta-1 and beta-2 gap junction proteins, respectively. This nomenclature emphasizes that GJB1 and GJB2 are more homologous to each other than either of them is to gap junction protein, alpha GJA1. Gap junction beta-2 protein is a member of the connexin protein family and plays a crucial role in forming gap junctions, which are channels that allow the transport of nutrients, ions, and signaling molecules between adjacent cells. GJB2 is widely expressed throughout the body, with particularly important functions in the inner ear and skin. In the cochlea, GJB2 is believed to be essential for maintaining proper potassium ion levels and for the maturation of certain cochlear cells, both of which are critical for the process of converting sound waves into electrical nerve impulses. In the skin, GJB2 contributes to the growth, maturation, and stability of the epidermis.

Clinical significance

Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1 (also known as connexin 26 deafness or GJB2-related deafness). One fairly common mutation is the deletion of one guanine from a string of six, resulting in a frameshift and termination of the protein at amino acid number 13. Having two copies of this mutation results in deafness. Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle. The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer, breast cancer, and bladder cancer. Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion and by stimulating the self-perpetuation ability of cancer stem cells.