TMC1_HUMAN
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 03-AUG-2022, entry version 147.
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], AND VARIANTS LYS-81; DFNA36 ASN-572 AND DFNB7
RP 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 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}.
CC -!- SUBUNIT: Interacts with TOMT. The interaction of TMC1 and TMC2 with
CC TOMT is required for the transportation of TMC1/2 into the stereocilia
CC of hair cells. Interacts (via N-terminus) with both isoforms CD1 and
CC CD3 of PCDH15. {ECO:0000250|UniProtKB:Q8R4P5}.
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};
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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; 6.
DR STRING; 9606.ENSP00000297784; -.
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; Q8TDI8; -.
DR PeptideAtlas; Q8TDI8; -.
DR PRIDE; Q8TDI8; -.
DR ProteomicsDB; 74293; -.
DR Antibodypedia; 27012; 54 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 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; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 90636; 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; RNKPWKM; -.
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 1059 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 buccal mucosa cell and 95 other tissues.
DR ExpressionAtlas; Q8TDI8; baseline and differential.
DR Genevisible; Q8TDI8; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0032426; C:stereocilium tip; IEA:Ensembl.
DR GO; GO:0008381; F:mechanosensitive 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; PTHR23302; 1.
DR Pfam; PF07810; TMC; 1.
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
