ID TMC1_HUMAN Reviewed; 760 AA. AC Q8TDI8; A8MVZ2; B1AM91; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 2. DT 27-MAR-2024, entry version 156. DE RecName: Full=Transmembrane channel-like protein 1; DE AltName: Full=Transmembrane cochlear-expressed protein 1; GN Name=TMC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-81, VARIANT DFNA36 ASN-572, AND RP VARIANT DFNB7 VAL-654. RC TISSUE=Fetal brain; RX PubMed=11850618; DOI=10.1038/ng842; RA Kurima K., Peters L.M., Yang Y., Riazuddin S., Ahmed Z.M., Naz S., RA Arnaud D., Drury S., Mo J., Makishima T., Ghosh M., Menon P.S.N., RA Deshmukh D., Oddoux C., Ostrer H., Khan S., Raizuddin S., Deininger P.L., RA Hampton L.L., Sullivan S.L., Battey J.F., Keats B.J.B., Wilcox E.R., RA Friedman T.B., Griffith A.J.; RT "Dominant and recessive deafness caused by mutations of a novel gene, TMC1, RT required for cochlear hair-cell function."; RL Nat. Genet. 30:277-284(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 460-760. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP INTERACTION WITH CIB2. RX PubMed=34089643; DOI=10.1016/j.neuron.2021.05.007; RA Liang X., Qiu X., Dionne G., Cunningham C.L., Pucak M.L., Peng G., RA Kim Y.H., Lauer A., Shapiro L., Mueller U.; RT "CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of RT hair cells."; RL Neuron 109:2131-2149(2021). RN [6] RP VARIANT DFNA36 ASN-572. RX PubMed=25388789; DOI=10.1186/s12967-014-0311-1; RA Wei Q., Zhu H., Qian X., Chen Z., Yao J., Lu Y., Cao X., Xing G.; RT "Targeted genomic capture and massively parallel sequencing to identify RT novel variants causing Chinese hereditary hearing loss."; RL J. Transl. Med. 12:311-311(2014). CC -!- FUNCTION: Probable ion channel required for the normal function of CC cochlear hair cells. {ECO:0000250|UniProtKB:Q8R4P5}. CC -!- SUBUNIT: Interacts with TOMT (By similarity). The interaction of TMC1 CC and TMC2 with TOMT is required for the transportation of TMC1/2 into CC the stereocilia of hair cells. Interacts (via N-terminus) with both CC isoforms CD1 and CD3 of PCDH15 (By similarity). Interacts with CIB2 CC (PubMed:34089643). Interacts with CIB3 (By similarity). CC {ECO:0000250|UniProtKB:Q8R4P5, ECO:0000269|PubMed:34089643}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8R4P5}; CC Multi-pass membrane protein {ECO:0000305}. Note=Localized to the CC stereocilia of the cochlear hair cells. {ECO:0000250|UniProtKB:Q8R4P5}. CC -!- TISSUE SPECIFICITY: Detected in fetal cochlea, and at low levels in CC placenta and testis. CC -!- DISEASE: Deafness, autosomal dominant, 36 (DFNA36) [MIM:606705]: A form CC of non-syndromic sensorineural hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. DFNA36 is a bilateral hearing loss, and begins at 5-10 CC years of age. It progresses to profound deafness within 10-15 years. CC {ECO:0000269|PubMed:11850618, ECO:0000269|PubMed:25388789}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Deafness, autosomal recessive, 7 (DFNB7) [MIM:600974]: A form CC of non-syndromic sensorineural hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. {ECO:0000269|PubMed:11850618}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC05351.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC05351.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF417578; AAL86399.1; -; mRNA. DR EMBL; AL591662; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL162416; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590662; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471089; EAW62541.1; -; Genomic_DNA. DR EMBL; AK098607; BAC05351.1; ALT_SEQ; mRNA. DR CCDS; CCDS6643.1; -. DR RefSeq; NP_619636.2; NM_138691.2. DR AlphaFoldDB; Q8TDI8; -. DR SMR; Q8TDI8; -. DR BioGRID; 125588; 9. DR IntAct; Q8TDI8; 7. DR STRING; 9606.ENSP00000494684; -. DR TCDB; 1.A.17.4.15; the calcium-dependent chloride channel (ca-clc) family. DR iPTMnet; Q8TDI8; -. DR PhosphoSitePlus; Q8TDI8; -. DR BioMuta; TMC1; -. DR DMDM; 212286376; -. DR jPOST; Q8TDI8; -. DR MassIVE; Q8TDI8; -. DR PaxDb; 9606-ENSP00000297784; -. DR PeptideAtlas; Q8TDI8; -. DR ProteomicsDB; 74293; -. DR Antibodypedia; 27012; 80 antibodies from 13 providers. DR DNASU; 117531; -. DR Ensembl; ENST00000297784.10; ENSP00000297784.6; ENSG00000165091.18. DR Ensembl; ENST00000340019.4; ENSP00000341433.3; ENSG00000165091.18. DR Ensembl; ENST00000645208.2; ENSP00000494684.1; ENSG00000165091.18. DR GeneID; 117531; -. DR KEGG; hsa:117531; -. DR MANE-Select; ENST00000297784.10; ENSP00000297784.6; NM_138691.3; NP_619636.2. DR UCSC; uc004aiz.1; human. DR AGR; HGNC:16513; -. DR CTD; 117531; -. DR DisGeNET; 117531; -. DR GeneCards; TMC1; -. DR GeneReviews; TMC1; -. DR HGNC; HGNC:16513; TMC1. DR HPA; ENSG00000165091; Tissue enhanced (cervix). DR MalaCards; TMC1; -. DR MIM; 600974; phenotype. DR MIM; 606705; phenotype. DR MIM; 606706; gene. DR neXtProt; NX_Q8TDI8; -. DR OpenTargets; ENSG00000165091; -. DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA38156; -. DR VEuPathDB; HostDB:ENSG00000165091; -. DR eggNOG; ENOG502QQGX; Eukaryota. DR GeneTree; ENSGT01050000244942; -. DR HOGENOM; CLU_013958_2_1_1; -. DR InParanoid; Q8TDI8; -. DR OMA; PCLPGIN; -. DR OrthoDB; 1275943at2759; -. DR PhylomeDB; Q8TDI8; -. DR TreeFam; TF313462; -. DR PathwayCommons; Q8TDI8; -. DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea. DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea. DR SignaLink; Q8TDI8; -. DR SIGNOR; Q8TDI8; -. DR BioGRID-ORCS; 117531; 7 hits in 1136 CRISPR screens. DR ChiTaRS; TMC1; human. DR GeneWiki; TMC1; -. DR GenomeRNAi; 117531; -. DR Pharos; Q8TDI8; Tbio. DR PRO; PR:Q8TDI8; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q8TDI8; Protein. DR Bgee; ENSG00000165091; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 96 other cell types or tissues. DR ExpressionAtlas; Q8TDI8; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0032426; C:stereocilium tip; IEA:Ensembl. DR GO; GO:0008381; F:mechanosensitive monoatomic ion channel activity; IBA:GO_Central. DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central. DR GO; GO:0060117; P:auditory receptor cell development; IEA:Ensembl. DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IBA:GO_Central. DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IEA:Ensembl. DR GO; GO:0060005; P:vestibular reflex; IBA:GO_Central. DR InterPro; IPR038900; TMC. DR InterPro; IPR012496; TMC_dom. DR PANTHER; PTHR23302:SF18; TRANSMEMBRANE CHANNEL-LIKE PROTEIN 1; 1. DR PANTHER; PTHR23302; TRANSMEMBRANE CHANNEL-RELATED; 1. DR Pfam; PF07810; TMC; 1. DR Genevisible; Q8TDI8; HS. PE 1: Evidence at protein level; KW Cell membrane; Deafness; Disease variant; Hearing; Ion channel; KW Ion transport; Membrane; Non-syndromic deafness; Reference proteome; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..760 FT /note="Transmembrane channel-like protein 1" FT /id="PRO_0000185380" FT TOPO_DOM 1..199 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 200..220 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 221..272 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 273..293 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 294..365 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 366..386 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 387..440 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 441..461 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 462..634 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 635..655 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 656..699 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 700..720 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 721..760 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..80 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..15 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 27..51 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 60..80 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 81 FT /note="E -> K (in dbSNP:rs1796993)" FT /evidence="ECO:0000269|PubMed:11850618" FT /id="VAR_052333" FT VARIANT 141 FT /note="R -> W (in dbSNP:rs11143384)" FT /id="VAR_052334" FT VARIANT 486 FT /note="M -> T (in dbSNP:rs17058153)" FT /id="VAR_052335" FT VARIANT 572 FT /note="D -> N (in DFNA36; dbSNP:rs121908072)" FT /evidence="ECO:0000269|PubMed:11850618, FT ECO:0000269|PubMed:25388789" FT /id="VAR_014125" FT VARIANT 654 FT /note="M -> V (in DFNB7; dbSNP:rs121908074)" FT /evidence="ECO:0000269|PubMed:11850618" FT /id="VAR_014126" FT CONFLICT 673 FT /note="M -> R (in Ref. 4; BAC05351)" FT /evidence="ECO:0000305" SQ SEQUENCE 760 AA; 87768 MW; 129D585A4B44EAAA CRC64; MSPKKVQIKV EEKEDETEES SSEEEEEVED KLPRRESLRP KRKRTRDVIN EDDPEPEPED EETRKAREKE RRRRLKRGAE EEEIDEEELE RLKAELDEKR QIIATVKCKP WKMEKKIEVL KEAKKFVSEN EGALGKGKGK RWFAFKMMMA KKWAKFLRDF ENFKAACVPW ENKIKAIESQ FGSSVASYFL FLRWMYGVNM VLFILTFSLI MLPEYLWGLP YGSLPRKTVP RAEEASAANF GVLYDFNGLA QYSVLFYGYY DNKRTIGWMN FRLPLSYFLV GIMCIGYSFL VVLKAMTKNI GDDGGGDDNT FNFSWKVFTS WDYLIGNPET ADNKFNSITM NFKEAITEEK AAQVEENVHL IRFLRFLANF FVFLTLGGSG YLIFWAVKRS QEFAQQDPDT LGWWEKNEMN MVMSLLGMFC PTLFDLFAEL EDYHPLIALK WLLGRIFALL LGNLYVFILA LMDEINNKIE EEKLVKANIT LWEANMIKAY NASFSENSTG PPFFVHPADV PRGPCWETMV GQEFVRLTVS DVLTTYVTIL IGDFLRACFV RFCNYCWCWD LEYGYPSYTE FDISGNVLAL IFNQGMIWMG SFFAPSLPGI NILRLHTSMY FQCWAVMCCN VPEARVFKAS RSNNFYLGML LLILFLSTMP VLYMIVSLPP SFDCGPFSGK NRMFEVIGET LEHDFPSWMA KILRQLSNPG LVIAVILVMV LAIYYLNATA KGQKAANLDL KKKMKMQALE NKMRNKKMAA ARAAAAAGRQ //