Q8R4P5 (TMC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	757 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Hearing Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	Ion channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	auditory receptor cell development Inferred from mutant phenotype PubMed 22105175. Source: MGI detection of mechanical stimulus involved in sensory perception of sound Inferred from mutant phenotype PubMed 22105175. Source: MGI ion transport Inferred from electronic annotation. Source: UniProtKB-KW vestibular reflex Inferred from genetic interaction PubMed 22105175. Source: MGI
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 16455951. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW stereocilium bundle tip Inferred from direct assay PubMed 22105175. Source: MGI
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 757	757	Transmembrane channel-like protein 1		PRO_0000185381
Regions
	Topological domain	1 – 193	193	Cytoplasmic Potential
	Transmembrane	194 – 214	21	Helical; Potential
	Topological domain	215 – 266	52	Extracellular Potential
	Transmembrane	267 – 287	21	Helical; Potential
	Topological domain	288 – 359	72	Cytoplasmic Potential
	Transmembrane	360 – 380	21	Helical; Potential
	Topological domain	381 – 434	54	Extracellular Potential
	Transmembrane	435 – 455	21	Helical; Potential
	Topological domain	456 – 631	176	Cytoplasmic Potential
	Transmembrane	632 – 652	21	Helical; Potential
	Topological domain	653 – 696	44	Extracellular Potential
	Transmembrane	697 – 717	21	Helical; Potential
	Topological domain	718 – 757	40	Cytoplasmic Potential
	Compositional bias	7 – 172	166	Arg/Asp/Glu/Lys-rich (highly charged)
	Compositional bias	746 – 754	9	Poly-Ala
Natural variations
	Alternative sequence	1 – 545	545	Missing in isoform 2.		VSP_006435
	Alternative sequence	546 – 562	17	FVRFC…LEYGY → MQQIPDALHSSPIALYE in isoform 2.		VSP_006436
	Alternative sequence	751 – 757	7	AAAAGGQ → GWRCGFVWRFCVPNSPYTLA LPMRHSMARHHRPWELIPRF LPSIISDLPKHLSEALISFP WEWIKKKKKDGKFQ in isoform 2.		VSP_006437
	Natural variant	412	1	M → K in BTH. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 9FB6CB73A7DD367D	FASTA	757	87,264
	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
	Isoform 2 [UniParc]. Checksum: 71E4F324D407716E	FASTA	279	31,965
	10 20 30 40 50 60 MQQIPDALHS SPIALYEPSY TEFDISGNVL ALIFNQGMIW MGSFFAPSLP GINILRLHTS 70 80 90 100 110 120 MYFQCWAVMC CNVPEARVFK ASRSNNFYLG MLLLILFLST MPVLYMIVSL PPSFDCGPFS 130 140 150 160 170 180 GKNRMFEVIG ETLEHDFPSW MAKILRQLSN PGLVIAVILV MVLTIYYLNA TAKGQKAANL 190 200 210 220 230 240 DLKKKMKQQA LENKMRNKKM AAARAGWRCG FVWRFCVPNS PYTLALPMRH SMARHHRPWE 250 260 270 LIPRFLPSII SDLPKHLSEA LISFPWEWIK KKKKDGKFQ

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00230747. IPI00331320.
RefSeq	NP_083229.1. NM_028953.2.
UniGene	Mm.219585.
3D structure databases
ModBase	Search...
Protein family/group databases
TCDB	9.B.99.1.1. transmembrane channel-like protein (TMC) family.
PTM databases
PhosphoSite	Q8R4P5.
Proteomic databases
PaxDb	Q8R4P5.
PRIDE	Q8R4P5.
Protocols and materials databases
DNASU	13409.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000039500; ENSMUSP00000040859; ENSMUSG00000024749.
GeneID	13409.
KEGG	mmu:13409.
UCSC	uc008gyo.1. mouse. uc008gyp.1. mouse.
Organism-specific databases
CTD	117531.
MGI	MGI:2151016. Tmc1.
Phylogenomic databases
eggNOG	NOG78939.
GeneTree	ENSGT00670000097681.
HOGENOM	HOG000231742.
HOVERGEN	HBG036209.
InParanoid	Q8R4P5.
OMA	CNVPEAR.
OrthoDB	EOG4P5K8P.
Gene expression databases
ArrayExpress	Q8R4P5.
Bgee	Q8R4P5.
CleanEx	MM_TMC1.
Genevestigator	Q8R4P5.
GermOnline	ENSMUSG00000024749. Mus musculus.
Family and domain databases
InterPro	IPR012496. TMC. [Graphical view]
Pfam	PF07810. TMC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	283811.
SOURCE	Search...

Entry information

Entry name

TMC1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program