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Q8R4P5 (TMC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane channel-like protein 1
Alternative name(s):
Beethoven protein
Deafness protein
Transmembrane cochlear-expressed protein 1
Gene names
Name:Tmc1
Synonyms:Bth, dn
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length757 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable ion channel required for the normal function of cochlear hair cells. Ref.1

Subcellular location

Membrane; Multi-pass membrane protein Potential.

Tissue specificity

Detected in cochlear inner and outer hair cells and in neurosensory epithelia of the vestibular end organs. Also expressed in cortex, cerebellum, eye, colon, ovary and testis. Ref.3

Developmental stage

Expressed at low, constant levels in temporal bone from embryonic day 14 to day 1 after birth. Increases by 8 to 16-fold at day 5, 10 and 20 and continues to be expressed up to day 90.

Involvement in disease

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. Ref.4

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.

Sequence similarities

Belongs to the TMC family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8R4P5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8R4P5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-545: Missing.
     546-562: FVRFCNYCWCWDLEYGY → MQQIPDALHSSPIALYE
     751-757: AAAAGGQ → GWRCGFVWRF...KKKKKDGKFQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 757757Transmembrane channel-like protein 1
PRO_0000185381

Regions

Topological domain1 – 193193Cytoplasmic Potential
Transmembrane194 – 21421Helical; Potential
Topological domain215 – 26652Extracellular Potential
Transmembrane267 – 28721Helical; Potential
Topological domain288 – 35972Cytoplasmic Potential
Transmembrane360 – 38021Helical; Potential
Topological domain381 – 43454Extracellular Potential
Transmembrane435 – 45521Helical; Potential
Topological domain456 – 631176Cytoplasmic Potential
Transmembrane632 – 65221Helical; Potential
Topological domain653 – 69644Extracellular Potential
Transmembrane697 – 71721Helical; Potential
Topological domain718 – 75740Cytoplasmic Potential
Compositional bias7 – 172166Arg/Asp/Glu/Lys-rich (highly charged)
Compositional bias746 – 7549Poly-Ala

Natural variations

Alternative sequence1 – 545545Missing in isoform 2.
VSP_006435
Alternative sequence546 – 56217FVRFC…LEYGY → MQQIPDALHSSPIALYE in isoform 2.
VSP_006436
Alternative sequence751 – 7577AAAAGGQ → GWRCGFVWRFCVPNSPYTLA LPMRHSMARHHRPWELIPRF LPSIISDLPKHLSEALISFP WEWIKKKKKDGKFQ in isoform 2.
VSP_006437
Natural variant4121M → K in BTH. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: 9FB6CB73A7DD367D

FASTA75787,264
        10         20         30         40         50         60 
MLQIQVEEKE EDTEESSSEE EEDKLPRRES LRPKRKRTRD VINEDDPEPE PEDEETRKAR 

        70         80         90        100        110        120 
EKERRRRLRR GAEEEEEIDE EELERLKALL DENRQMIATV KCKPWKMEKK IEVLKEAKKF 

       130        140        150        160        170        180 
VSENEGALGK GKGKKWFAFK MMMAKKWAKF LRDFENFKAA CVPWENKIKA IESQFGSSVA 

       190        200        210        220        230        240 
SYFLFLRWMY GVNMVLFVLT FSLIMLPEYL WGLPYGSLPR KTVPRAEEAS AANFGVLYDF 

       250        260        270        280        290        300 
NGLAQYSVLF YGYYDNKRTI GWLNFRLPLS YFLVGIMCIG YSFLVVLKAM TKNIGDDGGG 

       310        320        330        340        350        360 
DDNTFNFSWK VFCSWDYLIG NPETADNKFN SITMNFKEAI IEERAAQVEE NIHLIRFLRF 

       370        380        390        400        410        420 
LANFFVFLTL GASGYLIFWA VKRSQEFAQQ DPDTLGWWEK NEMNMVMSLL GMFCPTLFDL 

       430        440        450        460        470        480 
FAELEDYHPL IALKWLLGRI FALLLGNLYV FILALMDEIN NKIEEEKLVK ANITLWEANM 

       490        500        510        520        530        540 
IKAYNESLSG LSGNTTGAPF FVHPADVPRG PCWETMVGQE FVRLTVSDVL TTYVTILIGD 

       550        560        570        580        590        600 
FLRACFVRFC NYCWCWDLEY GYPSYTEFDI SGNVLALIFN QGMIWMGSFF APSLPGINIL 

       610        620        630        640        650        660 
RLHTSMYFQC WAVMCCNVPE ARVFKASRSN NFYLGMLLLI LFLSTMPVLY MIVSLPPSFD 

       670        680        690        700        710        720 
CGPFSGKNRM FEVIGETLEH DFPSWMAKIL RQLSNPGLVI AVILVMVLTI YYLNATAKGQ 

       730        740        750 
KAANLDLKKK MKQQALENKM RNKKMAAARA AAAAGGQ 

« Hide

Isoform 2 [UniParc].

Checksum: 71E4F324D407716E
Show »

FASTA27931,965

References

« Hide 'large scale' references
[1]"Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function."
Kurima K., Peters L.M., Yang Y., Riazuddin S., Ahmed Z.M., Naz S., Arnaud D., Drury S., Mo J., Makishima T., Ghosh M., Menon P.S.N., Deshmukh D., Oddoux C., Ostrer H., Khan S., Raizuddin S., Deininger P.L. expand/collapse author list , Hampton L.L., Sullivan S.L., Battey J.F., Keats B.J.B., Wilcox E.R., Friedman T.B., Griffith A.J.
Nat. Genet. 30:277-284(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Strain: BALB/c.
Tissue: Cochlea.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Testis.
[3]"TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins."
Keresztes G., Mutai H., Heller S.
BMC Genomics 4:24-24(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 522-658, TISSUE SPECIFICITY.
Strain: C57BL/6J.
[4]"Beethoven, a mouse model for dominant, progressive hearing loss DFNA36."
Vreugde S., Erven A., Kros C.J., Marcotti W., Fuchs H., Kurima K., Wilcox E.R., Friedman T.B., Griffith A.J., Balling R., Hrabe de Angelis M., Avraham K.B., Steel K.P.
Nat. Genet. 30:257-258(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BTH LYS-412.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF417579 mRNA. Translation: AAL86400.1.
AK016832 mRNA. No translation available.
AY263155 mRNA. Translation: AAP35263.1.
RefSeqNP_083229.1. NM_028953.2.
UniGeneMm.219585.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein family/group databases

TCDB1.A.17.4.6. the calcium-dependent chloride channel (ca-clc) family.

PTM databases

PhosphoSiteQ8R4P5.

Proteomic databases

PaxDbQ8R4P5.
PRIDEQ8R4P5.

Protocols and materials databases

DNASU13409.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000039500; ENSMUSP00000040859; ENSMUSG00000024749. [Q8R4P5-1]
GeneID13409.
KEGGmmu:13409.
UCSCuc008gyo.1. mouse. [Q8R4P5-2]
uc008gyp.1. mouse. [Q8R4P5-1]

Organism-specific databases

CTD117531.
MGIMGI:2151016. Tmc1.

Phylogenomic databases

eggNOGNOG78939.
GeneTreeENSGT00670000097681.
HOGENOMHOG000231742.
HOVERGENHBG036209.
InParanoidQ8R4P5.
OMAHTSMYFQ.
OrthoDBEOG7FR7FN.
PhylomeDBQ8R4P5.
TreeFamTF313462.

Gene expression databases

BgeeQ8R4P5.
CleanExMM_TMC1.
GenevestigatorQ8R4P5.

Family and domain databases

InterProIPR012496. TMC.
[Graphical view]
PfamPF07810. TMC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio283811.
PROQ8R4P5.
SOURCESearch...

Entry information

Entry nameTMC1_MOUSE
AccessionPrimary (citable) accession number: Q8R4P5
Secondary accession number(s): Q7TQB2, Q9D435
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: June 1, 2002
Last modified: April 16, 2014
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot