TMC1_MOUSE
ID TMC1_MOUSE Reviewed; 757 AA.
AC Q8R4P5; Q7TQB2; Q9D435;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Transmembrane channel-like protein 1;
DE AltName: Full=Beethoven protein;
DE AltName: Full=Deafness protein;
DE AltName: Full=Transmembrane cochlear-expressed protein 1;
GN Name=Tmc1; Synonyms=Bth, dn;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INVOLVEMENT IN
RP DEAFNESS.
RC STRAIN=BALB/cJ; TISSUE=Cochlea;
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 MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 522-658, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=12812529; DOI=10.1186/1471-2164-4-24;
RA Keresztes G., Mutai H., Heller S.;
RT "TMC and EVER genes belong to a larger novel family, the TMC gene family
RT encoding transmembrane proteins.";
RL BMC Genomics 4:24-24(2003).
RN [4]
RP VARIANT BTH LYS-412.
RX PubMed=11850623; DOI=10.1038/ng848;
RA Vreugde S., Erven A., Kros C.J., Marcotti W., Fuchs H., Kurima K.,
RA Wilcox E.R., Friedman T.B., Griffith A.J., Balling R., Hrabe de Angelis M.,
RA Avraham K.B., Steel K.P.;
RT "Beethoven, a mouse model for dominant, progressive hearing loss DFNA36.";
RL Nat. Genet. 30:257-258(2002).
RN [5]
RP INTERACTION WITH PCDH15, AND SUBCELLULAR LOCATION.
RX PubMed=25114259; DOI=10.1073/pnas.1402152111;
RA Maeda R., Kindt K.S., Mo W., Morgan C.P., Erickson T., Zhao H.,
RA Clemens-Grisham R., Barr-Gillespie P.G., Nicolson T.;
RT "Tip-link protein protocadherin 15 interacts with transmembrane channel-
RT like proteins TMC1 and TMC2.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12907-12912(2014).
RN [6]
RP INTERACTION WITH TOMT, AND SUBCELLULAR LOCATION.
RX PubMed=28504928; DOI=10.7554/elife.24318;
RA Cunningham C.L., Wu Z., Jafari A., Zhao B., Schrode K., Harkins-Perry S.,
RA Lauer A., Mueller U.;
RT "The murine catecholamine methyltransferase mTOMT is essential for
RT mechanotransduction by cochlear hair cells.";
RL Elife 6:0-0(2017).
RN [7]
RP INTERACTION WITH TOMT, AND SUBCELLULAR LOCATION.
RX PubMed=28534737; DOI=10.7554/elife.28474;
RA Erickson T., Morgan C.P., Olt J., Hardy K., Busch-Nentwich E., Maeda R.,
RA Clemens R., Krey J.F., Nechiporuk A., Barr-Gillespie P.G., Marcotti W.,
RA Nicolson T.;
RT "Integration of Tmc1/2 into the mechanotransduction complex in zebrafish
RT hair cells is regulated by Transmembrane O-methyltransferase (Tomt).";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Probable ion channel required for the normal function of
CC cochlear hair cells. {ECO:0000269|PubMed:11850618}.
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:0000269|PubMed:28504928,
CC ECO:0000269|PubMed:28534737}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25114259,
CC ECO:0000269|PubMed:28534737}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Localized to the stereocilia of the cochlear hair
CC cells. {ECO:0000269|PubMed:28504928}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R4P5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R4P5-2; Sequence=VSP_006435, VSP_006436, VSP_006437;
CC -!- TISSUE SPECIFICITY: Detected in cochlear inner and outer hair cells and
CC in neurosensory epithelia of the vestibular end organs. Also expressed
CC in cortex, cerebellum, eye, colon, ovary and testis.
CC {ECO:0000269|PubMed:12812529}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low, constant levels in temporal bone
CC from embryonic day 14 to day 1 after birth. Increases by 8 to 16-fold
CC at day 5, 10 and 20 and continues to be expressed up to day 90.
CC -!- DISEASE: Note=Defects in Tmc1 are the cause of the dominant deaf mutant
CC Beethoven (BTH). Heterozygotes show progressive hair-cell degeneration
CC from day 20 onwards, leading to severe depletion of inner hair cells
CC and scattered loss of outer hair cells, and progressive loss of the
CC Preyer reflex from around day 30. Homozygotes show almost complete
CC degeneration of inner hair cells, and little or no Preyer reflex at any
CC age.
CC -!- DISEASE: Note=Defects in Tmc1 are the cause of recessive deaf mutant
CC dn. The dn mutant shows profound deafness with degeneration of the
CC organ of Corti, stria vascularis, and occasionally the saccular macula,
CC starting at about 10 days after birth (PubMed:11850618).
CC {ECO:0000269|PubMed:11850618}.
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}.
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DR EMBL; AF417579; AAL86400.1; -; mRNA.
DR EMBL; AK016832; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY263155; AAP35263.1; -; mRNA.
DR CCDS; CCDS50403.1; -. [Q8R4P5-1]
DR RefSeq; NP_083229.1; NM_028953.2. [Q8R4P5-1]
DR PDB; 6WUD; X-ray; 1.84 A; B=298-352.
DR PDBsum; 6WUD; -.
DR AlphaFoldDB; Q8R4P5; -.
DR SMR; Q8R4P5; -.
DR STRING; 10090.ENSMUSP00000040859; -.
DR TCDB; 1.A.17.4.6; the calcium-dependent chloride channel (ca-clc) family.
DR iPTMnet; Q8R4P5; -.
DR PhosphoSitePlus; Q8R4P5; -.
DR MaxQB; Q8R4P5; -.
DR PaxDb; Q8R4P5; -.
DR PRIDE; Q8R4P5; -.
DR ProteomicsDB; 259471; -. [Q8R4P5-1]
DR Antibodypedia; 27012; 54 antibodies from 13 providers.
DR DNASU; 13409; -.
DR Ensembl; ENSMUST00000039500; ENSMUSP00000040859; ENSMUSG00000024749. [Q8R4P5-1]
DR GeneID; 13409; -.
DR KEGG; mmu:13409; -.
DR UCSC; uc008gyo.1; mouse. [Q8R4P5-2]
DR UCSC; uc008gyp.1; mouse. [Q8R4P5-1]
DR CTD; 117531; -.
DR MGI; MGI:2151016; Tmc1.
DR VEuPathDB; HostDB:ENSMUSG00000024749; -.
DR eggNOG; ENOG502QQGX; Eukaryota.
DR GeneTree; ENSGT01050000244942; -.
DR HOGENOM; CLU_013958_2_1_1; -.
DR InParanoid; Q8R4P5; -.
DR OMA; RNKPWKM; -.
DR OrthoDB; 310839at2759; -.
DR PhylomeDB; Q8R4P5; -.
DR TreeFam; TF313462; -.
DR BioGRID-ORCS; 13409; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Tmc1; mouse.
DR PRO; PR:Q8R4P5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8R4P5; protein.
DR Bgee; ENSMUSG00000024749; Expressed in spermatid and 37 other tissues.
DR ExpressionAtlas; Q8R4P5; baseline and differential.
DR Genevisible; Q8R4P5; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032426; C:stereocilium tip; IDA:MGI.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IMP:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:MGI.
DR GO; GO:0060117; P:auditory receptor cell development; IMP:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0060005; P:vestibular reflex; IMP:MGI.
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 3D-structure; Alternative splicing; Cell membrane; Deafness;
KW Disease variant; Hearing; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..757
FT /note="Transmembrane channel-like protein 1"
FT /id="PRO_0000185381"
FT TOPO_DOM 1..193
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..266
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 381..434
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..631
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 653..696
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 697..717
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 718..757
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..545
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006435"
FT VAR_SEQ 546..562
FT /note="FVRFCNYCWCWDLEYGY -> MQQIPDALHSSPIALYE (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006436"
FT VAR_SEQ 751..757
FT /note="AAAAGGQ -> GWRCGFVWRFCVPNSPYTLALPMRHSMARHHRPWELIPRFL
FT PSIISDLPKHLSEALISFPWEWIKKKKKDGKFQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006437"
FT VARIANT 412
FT /note="M -> K (in BTH)"
FT /evidence="ECO:0000269|PubMed:11850623"
FT HELIX 306..312
FT /evidence="ECO:0007829|PDB:6WUD"
FT HELIX 322..346
FT /evidence="ECO:0007829|PDB:6WUD"
SQ SEQUENCE 757 AA; 87264 MW; 9FB6CB73A7DD367D CRC64;
MLQIQVEEKE EDTEESSSEE EEDKLPRRES LRPKRKRTRD VINEDDPEPE PEDEETRKAR
EKERRRRLRR GAEEEEEIDE EELERLKALL DENRQMIATV KCKPWKMEKK IEVLKEAKKF
VSENEGALGK GKGKKWFAFK MMMAKKWAKF LRDFENFKAA CVPWENKIKA IESQFGSSVA
SYFLFLRWMY GVNMVLFVLT FSLIMLPEYL WGLPYGSLPR KTVPRAEEAS AANFGVLYDF
NGLAQYSVLF YGYYDNKRTI GWLNFRLPLS YFLVGIMCIG YSFLVVLKAM TKNIGDDGGG
DDNTFNFSWK VFCSWDYLIG NPETADNKFN SITMNFKEAI IEERAAQVEE NIHLIRFLRF
LANFFVFLTL GASGYLIFWA VKRSQEFAQQ DPDTLGWWEK NEMNMVMSLL GMFCPTLFDL
FAELEDYHPL IALKWLLGRI FALLLGNLYV FILALMDEIN NKIEEEKLVK ANITLWEANM
IKAYNESLSG LSGNTTGAPF FVHPADVPRG PCWETMVGQE FVRLTVSDVL TTYVTILIGD
FLRACFVRFC NYCWCWDLEY GYPSYTEFDI SGNVLALIFN QGMIWMGSFF APSLPGINIL
RLHTSMYFQC WAVMCCNVPE ARVFKASRSN NFYLGMLLLI LFLSTMPVLY MIVSLPPSFD
CGPFSGKNRM FEVIGETLEH DFPSWMAKIL RQLSNPGLVI AVILVMVLTI YYLNATAKGQ
KAANLDLKKK MKQQALENKM RNKKMAAARA AAAAGGQ
