Transmembrane channel-like protein 1 (TMC1) is a transmembrane protein encoded by TMC1 gene. It belongs to the transmembrane channel-like (TMC) protein family that is conserved from worms to humans. The mammalian genome encodes eight TMC genes, of which TMC1 and TMC2 are essential for hearing. TMC1 is located on chromosome 9q21 and contains 24 exons, which constitute the coding region of 2283 nucleotides. TMC1 encodes a protein required for the normal functioning of a mechanically activated channel, which is capable of sensory transduction in auditory and vestibular hair cells. The TMC1 protein localizes to the tip of the hair cell stereocilia, which is the site of conventional mechanical transduction. The TMC1 topology consists of six membrane-spanning domains with three extracellular loops, a large intracellular loop deposited between the transmembrane (TM) domains four and five, a long N-terminal and a short intracellular C-terminus. Its structure suggests that it can act as receptors, transport proteins, pumps or channels.
|Basic Information of TMC1|
|Protein Name||Transmembrane channel-like protein 1|
|Aliases||Transmembrane cochlear-expressed protein 1|
|Organism||Homo sapiens (Human)|
TMC1 is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. It plays a very critical role in conventional transduction in auditory and vestibular hair cells. TMC1 mRNA is specifically expressed in neurosensory hair cells of the inner ear and its mutations are associated with hearing loss. Mutations of TMC1 gene in humans and mice can result in a non-syndromic dominant or recessive hearing loss at the DFNA36 and DFNB7/B11 loci, respectively, on chromosome 9q13-q21. TMC1 mutations are a common cause of autosomal recessive nonsyndromic deafness, particularly in the Indian, Pakistani, Turkish and Tunisian families. In addition, the specific cellular function of TMCs is unknown. Nevertheless, it has been speculated that the TMC proteins are either ion channels, transporters, or modulators of such.
Fig.1 Structure of TMC1. TMC1 contains six transmembrane cells (S1 to S6) with intracellular N- and C-termini, and a long intracellular loop between domains S4 and S5. Point mutations that cause deafness in mice are indicated by red circles and the hatched segment indicates amino acid deletions, with residue numbers referring to mouse sequences. Point mutations causing deafness in humans are indicated by pink circles, with residue numbers referring to mouse sequences. (Robert, 2016)
This study finds that TMC1 is a pore-forming subunit of the hair cell mechanotransduction (MET) channel complex.
This article finds that there are different numbers of channels per MET complex and each channel requires multiple TMC1 molecules, which operate together in a coordinated or collaborative manner.
This article identifies four pathogenic variants of TMC1, suggesting that TMC1 may be the more common cause of hearing loss than expected.
This study analyzes the spectrum and founder effects of TMC1 mutations in non-syndromic deaf patients in Xiamen and shows that haplotype analysis is useful to understand the founder effect of the hot spot mutation.
This study demonstrates for the first time that TMC1 is a transmembrane protein.
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