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TMC1 Membrane Protein Introduction

Introduction of TMC1

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
Gene Name TMC1
Aliases Transmembrane cochlear-expressed protein 1
Organism Homo sapiens (Human)
UniProt ID Q8TDI8
Transmembrane Times 6
Length (aa) 760
Sequence MSPKKVQIKVEEKEDETEESSSEEEEEVEDKLPRRESLRPKRKRTRDVINEDDPEPEPEDEETRKAREKERRRRLKRGAEEEEIDEEELERLKAELDEKRQIIATVKCKPWKMEKKIEVLKEAKKFVSENEGALGKGKGKRWFAFKMMMAKKWAKFLRDFENFKAACVPWENKIKAIESQFGSSVASYFLFLRWMYGVNMVLFILTFSLIMLPEYLWGLPYGSLPRKTVPRAEEASAANFGVLYDFNGLAQYSVLFYGYYDNKRTIGWMNFRLPLSYFLVGIMCIGYSFLVVLKAMTKNIGDDGGGDDNTFNFSWKVFTSWDYLIGNPETADNKFNSITMNFKEAITEEKAAQVEENVHLIRFLRFLANFFVFLTLGGSGYLIFWAVKRSQEFAQQDPDTLGWWEKNEMNMVMSLLGMFCPTLFDLFAELEDYHPLIALKWLLGRIFALLLGNLYVFILALMDEINNKIEEEKLVKANITLWEANMIKAYNASFSENSTGPPFFVHPADVPRGPCWETMVGQEFVRLTVSDVLTTYVTILIGDFLRACFVRFCNYCWCWDLEYGYPSYTEFDISGNVLALIFNQGMIWMGSFFAPSLPGINILRLHTSMYFQCWAVMCCNVPEARVFKASRSNNFYLGMLLLILFLSTMPVLYMIVSLPPSFDCGPFSGKNRMFEVIGETLEHDFPSWMAKILRQLSNPGLVIAVILVMVLAIYYLNATAKGQKAANLDLKKKMKMQALENKMRNKKMAAARAAAAAGRQ

The Function of TMC1 Membrane Protein

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.

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. 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)

Application of TMC1 Membrane Protein in Literature

  1. Ballesteros A., et al. Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins. Elife. 2018, 7. PubMed ID: 30063209

    This study finds that TMC1 is a pore-forming subunit of the hair cell mechanotransduction (MET) channel complex.

  2. Beurg M., et al. Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea. Nature Communications. 2018, 9(1):2185. PubMed ID: 29872055

    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.

  3. Wang H., et al. Identification of four TMC1 variations in different Chinese families with hereditary hearing loss. Molecular Genetics & Genomic Medicine. 2018. PubMed ID: 29654653

    This article identifies four pathogenic variants of TMC1, suggesting that TMC1 may be the more common cause of hearing loss than expected.

  4. Jiang Y., et al. Mutation spectra and founder effect of TMC1 in patients with non-syndromic deafness in Xiamen area, China. American Journal of Medical Genetics Part B Neuropsychiatric Genetics. 2018, 177(3):301-307. PubMed ID: 29533536

    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.

  5. Labay V., et al. Topology of transmembrane channel-like gene 1 protein. Biochemistry. 2010, 49(39):8592-8. PubMed ID: 20672865

    This study demonstrates for the first time that TMC1 is a transmembrane protein.

TMC1 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TMC1 antibody development services.


During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

  1. Fettiplace Robert. (2016). Is TMC1 the Hair Cell Mechanotransducer Channel? Biophysical Journal. 111(1):3-9.

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