Tmc1
entrez
13409
canonical
uniprot
Q8R4P5
canonical
ensembl
ENSMUSG00000024749
resolver
ensp
ENSMUSP00000040859
resolver
genesymbol
Tmc1
resolver
genesymbol_syn
Bth
resolver
genesymbol_syn
TMC1ex1
resolver
genesymbol_syn
dn
resolver
uniprot
A0A6S6MPY2
resolver
uniprot
Q7TQB2
resolver
uniprot
Q9D435
resolver
uniprot_entry
A0A6S6MPY2_MOUSE
resolver
uniprot_entry
TMC1_MOUSE
resolver
uniprot_sec
Q7TQB2
resolver
uniprot_sec
Q9D435
resolver
amino_acid_sequence
MLQIQVEEKEEDTEESSSEEEEDKLPRRESLRPKRKRTRDVINEDDPEPEPEDEETRKAREKERRRRLRRGAEEEEEIDEEELERLKALLDENRQMIATVKCKPWKMEKKIEVLKEAKKFVSENEGALGKGKGKKWFAFKMMMAKKWAKFLRDFENFKAACVPWENKIKAIESQFGSSVASYFLFLRWMYGVNMVLFVLTFSLIMLPEYLWGLPYGSLPRKTVPRAEEASAANFGVLYDFNGLAQYSVLFYGYYDNKRTIGWLNFRLPLSYFLVGIMCIGYSFLVVLKAMTKNIGDDGGGDDNTFNFSWKVFCSWDYLIGNPETADNKFNSITMNFKEAIIEERAAQVEENIHLIRFLRFLANFFVFLTLGASGYLIFWAVKRSQEFAQQDPDTLGWWEKNEMNMVMSLLGMFCPTLFDLFAELEDYHPLIALKWLLGRIFALLLGNLYVFILALMDEINNKIEEEKLVKANITLWEANMIKAYNESLSGLSGNTTGAPFFVHPADVPRGPCWETMVGQEFVRLTVSDVLTTYVTILIGDFLRACFVRFCNYCWCWDLEYGYPSYTEFDISGNVLALIFNQGMIWMGSFFAPSLPGINILRLHTSMYFQCWAVMCCNVPEARVFKASRSNNFYLGMLLLILFLSTMPVLYMIVSLPPSFDCGPFSGKNRMFEVIGETLEHDFPSWMAKILRQLSNPGLVIAVILVMVLTIYYLNATAKGQKAANLDLKKKMKQQALENKMRNKKMAAARAAAAAGGQ
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Tmc1 are the cause of the dominant deaf mutant Beethoven (BTH). Heterozygotes show progressive hair-cell degeneration from day 20 onwards, leading to severe depletion of inner hair cells and scattered loss of outer hair cells, and progressive loss of the Preyer reflex from around day 30. Homozygotes show almost complete degeneration of inner hair cells, and little or no Preyer reflex at any age. {ECO:0000269|PubMed:11850623, ECO:0000269|PubMed:36191207}.; DISEASE: Note=Defects in Tmc1 are the cause of recessive deaf mutant dn. The dn mutant shows profound deafness with degeneration of the organ of Corti, stria vascularis, and occasionally the saccular macula, starting at about 10 days after birth (PubMed:11850618). {ECO:0000269|PubMed:11850618}.
uniprot
proteins
function
FUNCTION: Pore-forming subunit of the mechanotransducer (MET) non-selective cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system (PubMed:11850618, PubMed:23871232, PubMed:30138589, PubMed:36191207). The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, the tip-link PCDH15, and possibly the PIEZO subunits (PubMed:30138589, PubMed:36191207). MET channel is activated by tension in the tip-link extending from the side wall of one stereocilium to the tip of the adjacent shorter stereocilium, where the channel is located (PubMed:30138589, PubMed:36191207). TMC1 MET channel is highly permeable to calcium and likely transports monovalent cations (PubMed:23871232, PubMed:30138589, PubMed:36191207). Also involved in vestibular hair cells transduction current (PubMed:23871232). {ECO:0000269|PubMed:11850618, ECO:0000269|PubMed:23871232, ECO:0000269|PubMed:30138589, ECO:0000269|PubMed:36191207}.
uniprot
proteins
mass_dalton
87264
uniprot
proteins
mutagenesis
MUTAGEN 312; /note="F->R: Disrupts interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 315; /note="W->D: Disrupts interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 317; /note="Y->A: Disrupts interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 321; /note="N->K: No impact on interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 323; /note="E->K: No impact on interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 332; /note="I->D: Disrupts interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 336; /note="F->D: Disrupts interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 337; /note="K->Q: No impact on interaction with CIB2 and CIB3."; /evidence="ECO:0000269|PubMed:34089643"; MUTAGEN 416; /note="T->K: Reduced Ca(2+) permeability. No change in channel conductance."; /evidence="ECO:0000269|PubMed:36191207"; MUTAGEN 447; /note="N->C: Reduced sensory transduction current."; /evidence="ECO:0000269|PubMed:30138589"; MUTAGEN 520; /note="E->Q: Reduced Ca(2+) permeability. Reduced channel conductance."; /evidence="ECO:0000269|PubMed:36191207"; MUTAGEN 528; /note="D->C: Reduced sensory transduction current."; /evidence="ECO:0000269|PubMed:30138589"; MUTAGEN 528; /note="D->N: Reduced Ca(2+) permeability. Reduced channel conductance."; /evidence="ECO:0000269|PubMed:36191207"; MUTAGEN 554; /note="W->L: Reduced Ca(2+) permeability. Reduced channel expression without affecting conductance."; /evidence="ECO:0000269|PubMed:36191207"; MUTAGEN 569; /note="D->A: Reduced single-channel currents."; /evidence="ECO:0000269|PubMed:30138589"; MUTAGEN 569; /note="D->N: Reduced Ca(2+) permeability. Reduced channel expression without affecting conductance."; /evidence="ECO:0000269|PubMed:36191207
uniprot
proteins
protein_family
TMC family
uniprot
proteins
pubmed
11850618
uniprot
proteins
pubmed
11850623
uniprot
proteins
pubmed
12812529
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
23871232
uniprot
proteins
pubmed
25114259
uniprot
proteins
pubmed
28504928
uniprot
proteins
pubmed
28534737
uniprot
proteins
pubmed
28663585
uniprot
proteins
pubmed
30138589
uniprot
proteins
pubmed
34089643
uniprot
proteins
pubmed
36191207
uniprot
proteins
pubmed
38228630
uniprot
proteins
sequence_length
757
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25114259, ECO:0000269|PubMed:28534737}; Multi-pass membrane protein {ECO:0000305}. Note=Localized to the stereocilia tips of the cochlear hair cells. {ECO:0000269|PubMed:28504928, ECO:0000269|PubMed:38228630}.
uniprot
proteins
transmembrane_region
TRANSMEM 177..214; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 266..297; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 354..384; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 397..424; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 429..463; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 513..550; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 570..590; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 594..616; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 631..654; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3"; TRANSMEM 698..731; /note="Helical"; /evidence="ECO:0000250|UniProtKB:D3KZG3
uniprot
proteins