Q8TDI8 (TMC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane channel-like protein 1

Alternative name(s):
Transmembrane cochlear-expressed protein 1

Gene names

Name:

TMC1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	760 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the normal function of cochlear hair cells By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Detected in fetal cochlea, and at low levels in placenta and testis.
Involvement in disease	Defects in TMC1 are the cause of deafness autosomal dominant type 36 (DFNA36) [MIM:606705]. DFNA36 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA36 is a bilateral hearing loss, and begins at 5-10 years of age. It progresses to profound deafness within 10-15 years. Ref.1 Defects in TMC1 are the cause of deafness autosomal recessive type 7 (DFNB7) [MIM:600974]; also known as autosomal recessive neurosensory deafness type 11 (DFNB11). This hearing loss is congenital and profound.
Sequence similarities	Belongs to the TMC family.
Sequence caution	The sequence BAC05351.1 differs from that shown. Reason: Erroneous termination at position 744. Translated as Arg. The sequence BAC05351.1 differs from that shown. Reason: Frameshift at position 588.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 760	760	Transmembrane channel-like protein 1		PRO_0000185380
Regions
	Topological domain	1 – 199	199	Cytoplasmic Potential
	Transmembrane	200 – 220	21	Helical; Potential
	Topological domain	221 – 272	52	Extracellular Potential
	Transmembrane	273 – 293	21	Helical; Potential
	Topological domain	294 – 365	72	Cytoplasmic Potential
	Transmembrane	366 – 386	21	Helical; Potential
	Topological domain	387 – 440	54	Extracellular Potential
	Transmembrane	441 – 461	21	Helical; Potential
	Topological domain	462 – 634	173	Cytoplasmic Potential
	Transmembrane	635 – 655	21	Helical; Potential
	Topological domain	656 – 699	44	Extracellular Potential
	Transmembrane	700 – 720	21	Helical; Potential
	Topological domain	721 – 760	40	Cytoplasmic Potential
	Compositional bias	4 – 178	175	Arg/Asp/Glu/Lys-rich (highly charged)
	Compositional bias	749 – 757	9	Poly-Ala
Natural variations
	Natural variant	81	1	E → K. Ref.1 Corresponds to variant rs1796993 [ dbSNP | Ensembl ].		VAR_052333
	Natural variant	141	1	R → W. Corresponds to variant rs11143384 [ dbSNP | Ensembl ].		VAR_052334
	Natural variant	486	1	M → T. Corresponds to variant rs17058153 [ dbSNP | Ensembl ].		VAR_052335
	Natural variant	572	1	D → N in DFNA36. Ref.1		VAR_014125
	Natural variant	654	1	M → V in DFNB7. Ref.1		VAR_014126
Experimental info
	Sequence conflict	673	1	M → R in BAC05351. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q8TDI8 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: 129D585A4B44EAAA	FASTA	760	87,768
	10 20 30 40 50 60 MSPKKVQIKV EEKEDETEES SSEEEEEVED KLPRRESLRP KRKRTRDVIN EDDPEPEPED 70 80 90 100 110 120 EETRKAREKE RRRRLKRGAE EEEIDEEELE RLKAELDEKR QIIATVKCKP WKMEKKIEVL 130 140 150 160 170 180 KEAKKFVSEN EGALGKGKGK RWFAFKMMMA KKWAKFLRDF ENFKAACVPW ENKIKAIESQ 190 200 210 220 230 240 FGSSVASYFL FLRWMYGVNM VLFILTFSLI MLPEYLWGLP YGSLPRKTVP RAEEASAANF 250 260 270 280 290 300 GVLYDFNGLA QYSVLFYGYY DNKRTIGWMN FRLPLSYFLV GIMCIGYSFL VVLKAMTKNI 310 320 330 340 350 360 GDDGGGDDNT FNFSWKVFTS WDYLIGNPET ADNKFNSITM NFKEAITEEK AAQVEENVHL 370 380 390 400 410 420 IRFLRFLANF FVFLTLGGSG YLIFWAVKRS QEFAQQDPDT LGWWEKNEMN MVMSLLGMFC 430 440 450 460 470 480 PTLFDLFAEL EDYHPLIALK WLLGRIFALL LGNLYVFILA LMDEINNKIE EEKLVKANIT 490 500 510 520 530 540 LWEANMIKAY NASFSENSTG PPFFVHPADV PRGPCWETMV GQEFVRLTVS DVLTTYVTIL 550 560 570 580 590 600 IGDFLRACFV RFCNYCWCWD LEYGYPSYTE FDISGNVLAL IFNQGMIWMG SFFAPSLPGI 610 620 630 640 650 660 NILRLHTSMY FQCWAVMCCN VPEARVFKAS RSNNFYLGML LLILFLSTMP VLYMIVSLPP 670 680 690 700 710 720 SFDCGPFSGK NRMFEVIGET LEHDFPSWMA KILRQLSNPG LVIAVILVMV LAIYYLNATA 730 740 750 760 KGQKAANLDL KKKMKMQALE NKMRNKKMAA ARAAAAAGRQ

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: 11850618] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LYS-81; DFNA36 ASN-572 AND DFNB7 VAL-654. Tissue: Fetal brain.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 460-760. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF417578 mRNA. Translation: AAL86399.1. AL591662, AL162416, AL590662 Genomic DNA. Translation: CAH72029.1. AL162416, AL590662, AL591662 Genomic DNA. Translation: CAH72129.1. AL590662, AL162416, AL591662 Genomic DNA. Translation: CAI15164.1. CH471089 Genomic DNA. Translation: EAW62541.1. AK098607 mRNA. Translation: BAC05351.1. Sequence problems.
IPI	IPI00291387.
RefSeq	NP_619636.2. NM_138691.2.
UniGene	Hs.670211.
3D structure databases
ProteinModelPortal	Q8TDI8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8TDI8. 1 interaction.
STRING	Q8TDI8.
Polymorphism databases
DMDM	212286376.
Proteomic databases
PRIDE	Q8TDI8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297784; ENSP00000297784; ENSG00000165091. ENST00000340019; ENSP00000341433; ENSG00000165091. ENST00000396237; ENSP00000379538; ENSG00000165091.
GeneID	117531.
KEGG	hsa:117531.
Organism-specific databases
CTD	117531.
GeneCards	GC09P075137.
H-InvDB	HIX0008098.
HGNC	HGNC:16513. TMC1.
MIM	600974. phenotype. 606705. phenotype. 606706. gene.
neXtProt	NX_Q8TDI8.
Orphanet	90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA. 90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKB	PA38156.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13476.
GeneTree	ENSGT00550000074255.
HOGENOM	HBG716626.
HOVERGEN	HBG036209.
OMA	GNLYVFI.
OrthoDB	EOG4P5K8P.
PhylomeDB	Q8TDI8.
Gene expression databases
ArrayExpress	Q8TDI8.
Bgee	Q8TDI8.
CleanEx	HS_TMC1.
Genevestigator	Q8TDI8.
GermOnline	ENSG00000165091. Homo sapiens.
Family and domain databases
InterPro	IPR012496. TMC. [Graphical view]
Pfam	PF07810. TMC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	80206.
SOURCE	Search...

Entry information

Entry name

TMC1_HUMAN

Accession

Primary (citable) accession number: Q8TDI8
Secondary accession number(s): A8MVZ2, B1AM91

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 19, 2002
Last sequence update:	July 22, 2008
Last modified:	January 25, 2012
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.