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1.A.17.4.6
Transmembrane channel-like protein-1, Tmc1. Also called Transmembrane cochlear-expressed protein-1, Beethoven protein and deafness protein.  Required for normal function of cochlear hair cells, possibly as a Na+/K+/Ca2+ channel (Kim and Fettiplace 2013).  TMC1 and TMC2 are both components of hair cell transduction channels and contribute to permeation properties (Pan et al. 2013; Kawashima et al. 2014).  Channel activity has been demonstrated for the C. elegans orthologue, and the mouse Tmc1.  The C. elegans Tmc1 is probably a Na+-activated Na+-selective mechanosensor. The C. elegans Tmc2 may be a Na+/K+ channel.  The mouse Tmc1 is functional and replaces Tmc2 when expressed in C. elegans (WR Schafer, personal communication).  Ca2+ currents are blocked by the peptide toxin GsMTx-4 (Beurg et al. 2014).  Tmc1 and Tmc2, expressed in cochlear and vestibular hair cells, are required for hair cell mechanoelectric transduction (Nakanishi et al. 2014); mutations disrupt mechanoelectric transduction and are a cause of autosomal dominant and recessive forms of nonsyndromic hearing loss (Gao et al. 2015).  Using the mutant mouse model (Tmc1; Beethoven) for progressive hearing loss in humans (DFNA36) this mutation has been shown to affect the MET channel pore, reducing its Ca2+ permeability and its affinity for the permeant blocker, dihydrostreptomycin (Corns et al. 2016).  Evidence for TMC1 beiing the hair cell mechanosensitive channel has been evaluated (Fettiplace 2016).  The human orthologue (UniProt acc # Q8TDI8) is 96% identical.

Accession Number:Q8R4P5
Protein Name:Transmembrane channel-like protein 1
Length:757
Molecular Weight:87264.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Na+, K+, Ca2+

Cross database links:

Genevestigator: Q8R4P5
eggNOG: roNOG13961
HEGENOM: HBG716626

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FASTA formatted sequence
1:	MLQIQVEEKE EDTEESSSEE EEDKLPRRES LRPKRKRTRD VINEDDPEPE PEDEETRKAR 
61:	EKERRRRLRR GAEEEEEIDE EELERLKALL DENRQMIATV KCKPWKMEKK IEVLKEAKKF 
121:	VSENEGALGK GKGKKWFAFK MMMAKKWAKF LRDFENFKAA CVPWENKIKA IESQFGSSVA 
181:	SYFLFLRWMY GVNMVLFVLT FSLIMLPEYL WGLPYGSLPR KTVPRAEEAS AANFGVLYDF 
241:	NGLAQYSVLF YGYYDNKRTI GWLNFRLPLS YFLVGIMCIG YSFLVVLKAM TKNIGDDGGG 
301:	DDNTFNFSWK VFCSWDYLIG NPETADNKFN SITMNFKEAI IEERAAQVEE NIHLIRFLRF 
361:	LANFFVFLTL GASGYLIFWA VKRSQEFAQQ DPDTLGWWEK NEMNMVMSLL GMFCPTLFDL 
421:	FAELEDYHPL IALKWLLGRI FALLLGNLYV FILALMDEIN NKIEEEKLVK ANITLWEANM 
481:	IKAYNESLSG LSGNTTGAPF FVHPADVPRG PCWETMVGQE FVRLTVSDVL TTYVTILIGD 
541:	FLRACFVRFC NYCWCWDLEY GYPSYTEFDI SGNVLALIFN QGMIWMGSFF APSLPGINIL 
601:	RLHTSMYFQC WAVMCCNVPE ARVFKASRSN NFYLGMLLLI LFLSTMPVLY MIVSLPPSFD 
661:	CGPFSGKNRM FEVIGETLEH DFPSWMAKIL RQLSNPGLVI AVILVMVLTI YYLNATAKGQ 
721:	KAANLDLKKK MKQQALENKM RNKKMAAARA AAAAGGQ