TMC2_HUMAN
ID TMC2_HUMAN Reviewed; 906 AA.
AC Q8TDI7; Q5JXT0; Q5JXT1; Q6UWW4; Q6ZS41; Q8N9F3; Q9BYN2; Q9BYN3; Q9BYN4;
AC Q9BYN5;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Transmembrane channel-like protein 2;
DE AltName: Full=Transmembrane cochlear-expressed protein 2;
GN Name=TMC2; Synonyms=C20orf145; ORFNames=UNQ907/PRO1928;
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] (ISOFORM 1), VARIANT LYS-123, AND FUNCTION.
RC TISSUE=Brain, Inner ear, and Testis;
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 SEQUENCE REVISION.
RA Kurima K., Griffith A.J., Friedman T.B.;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 427-906 (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 693-906 (ISOFORM 3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
CC -!- FUNCTION: Probable ion channel required for the normal function of
CC cochlear hair cells (PubMed:11850618). Component of the hair cell's
CC mechanotransduction (MET) machinery. Involved in mechanosensitive
CC responses of the hair cells (By similarity).
CC {ECO:0000250|UniProtKB:E7FFT2, 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:0000250|UniProtKB:Q8R4P4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:E7FFT2};
CC Multi-pass membrane protein {ECO:0000305}. Note=Localized to the
CC stereocilia of the cochlear hair cells. {ECO:0000250|UniProtKB:Q8R4P4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TDI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDI7-3; Sequence=VSP_015281, VSP_015282;
CC Name=3;
CC IsoId=Q8TDI7-4; Sequence=VSP_015279, VSP_015283, VSP_015284;
CC -!- TISSUE SPECIFICITY: Detected in fetal cochlea.
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88976.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC04423.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF417580; AAL86401.2; -; mRNA.
DR EMBL; AK094789; BAC04423.1; ALT_INIT; mRNA.
DR EMBL; AK127751; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL049712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY358613; AAQ88976.1; ALT_INIT; mRNA.
DR CCDS; CCDS13029.2; -. [Q8TDI7-1]
DR RefSeq; NP_542789.2; NM_080751.2. [Q8TDI7-1]
DR AlphaFoldDB; Q8TDI7; -.
DR SMR; Q8TDI7; -.
DR BioGRID; 125589; 1.
DR IntAct; Q8TDI7; 1.
DR STRING; 9606.ENSP00000351732; -.
DR iPTMnet; Q8TDI7; -.
DR PhosphoSitePlus; Q8TDI7; -.
DR BioMuta; TMC2; -.
DR DMDM; 313104275; -.
DR PaxDb; Q8TDI7; -.
DR PeptideAtlas; Q8TDI7; -.
DR PRIDE; Q8TDI7; -.
DR Antibodypedia; 23203; 64 antibodies from 16 providers.
DR DNASU; 117532; -.
DR Ensembl; ENST00000358864.2; ENSP00000351732.1; ENSG00000149488.14. [Q8TDI7-1]
DR GeneID; 117532; -.
DR KEGG; hsa:117532; -.
DR MANE-Select; ENST00000358864.2; ENSP00000351732.1; NM_080751.3; NP_542789.2.
DR UCSC; uc002wgf.1; human. [Q8TDI7-1]
DR CTD; 117532; -.
DR DisGeNET; 117532; -.
DR GeneCards; TMC2; -.
DR HGNC; HGNC:16527; TMC2.
DR HPA; ENSG00000149488; Tissue enhanced (lung, pituitary gland).
DR MIM; 606707; gene.
DR neXtProt; NX_Q8TDI7; -.
DR OpenTargets; ENSG00000149488; -.
DR PharmGKB; PA38158; -.
DR VEuPathDB; HostDB:ENSG00000149488; -.
DR eggNOG; ENOG502QVCF; Eukaryota.
DR GeneTree; ENSGT01050000244942; -.
DR HOGENOM; CLU_013958_2_0_1; -.
DR InParanoid; Q8TDI7; -.
DR OMA; HAPSQTH; -.
DR OrthoDB; 310839at2759; -.
DR PhylomeDB; Q8TDI7; -.
DR TreeFam; TF313462; -.
DR PathwayCommons; Q8TDI7; -.
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; Q8TDI7; -.
DR SIGNOR; Q8TDI7; -.
DR BioGRID-ORCS; 117532; 10 hits in 1060 CRISPR screens.
DR ChiTaRS; TMC2; human.
DR GeneWiki; TMC2; -.
DR GenomeRNAi; 117532; -.
DR Pharos; Q8TDI7; Tbio.
DR PRO; PR:Q8TDI7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8TDI7; protein.
DR Bgee; ENSG00000149488; Expressed in cerebellar hemisphere and 77 other tissues.
DR ExpressionAtlas; Q8TDI7; baseline and differential.
DR Genevisible; Q8TDI7; HS.
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:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:UniProtKB.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..906
FT /note="Transmembrane channel-like protein 2"
FT /id="PRO_0000185382"
FT TOPO_DOM 1..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 358..431
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..508
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 530..693
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 694..714
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 715..750
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..906
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..906
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 800..820
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 821..868
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..644
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_015279"
FT VAR_SEQ 625..665
FT /note="PSYAEFDISGNVLGLIFNQGMIWMGSFYAPGLVGINVLRLL -> VGHHFMD
FT IPHKGISTIFFDTYSQMHSWAFHFFGSLMTVSAL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015281"
FT VAR_SEQ 666..906
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015282"
FT VAR_SEQ 727..806
FT /note="SGKNRMYDVLQETIENDFPTFLGKIFAFLANPGLIIPAILLMFLAIYYLNSV
FT SKSLSRANAQLRKKIQVLREVEKSHKSV -> RCRVSVAREHLPSRGSLLRGPRPRIPV
FT LVSCQPVKGHGTLGESPMPFKRVFCQDGNVRSFCVCAVHFSSHQPPVAVECLK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_015283"
FT VAR_SEQ 807..906
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_015284"
FT VARIANT 123
FT /note="R -> K (in dbSNP:rs6050063)"
FT /evidence="ECO:0000269|PubMed:11850618"
FT /id="VAR_023360"
FT VARIANT 205
FT /note="Q -> R (in dbSNP:rs11908093)"
FT /id="VAR_057281"
FT VARIANT 217
FT /note="W -> R (in dbSNP:rs34884202)"
FT /id="VAR_057282"
FT VARIANT 573
FT /note="S -> C (in dbSNP:rs16987592)"
FT /id="VAR_030621"
FT VARIANT 589
FT /note="S -> C (in dbSNP:rs16987592)"
FT /id="VAR_057283"
FT VARIANT 800
FT /note="E -> Q (in dbSNP:rs768537423)"
FT /id="VAR_030622"
FT VARIANT 816
FT /note="E -> Q (in dbSNP:rs6115242)"
FT /id="VAR_057284"
SQ SEQUENCE 906 AA; 102610 MW; 0EB7A3E35C870E2A CRC64;
MSHQVKGLKE EARGGVKGRV KSGSPHTGDR LGRRSSSKRA LKAEGTPGRR GAQRSQKERA
GGSPSPGSPR RKQTGRRRHR EELGEQERGE AERTCEGRRK RDERASFQER TAAPKREKEI
PRREEKSKRQ KKPRSSSLAS SASGGESLSE EELAQILEQV EEKKKLIATM RSKPWPMAKK
LTELREAQEF VEKYEGALGK GKGKQLYAYK MLMAKKWVKF KRDFDNFKTQ CIPWEMKIKD
IESHFGSSVA SYFIFLRWMY GVNLVLFGLI FGLVIIPEVL MGMPYGSIPR KTVPRAEEEK
AMDFSVLWDF EGYIKYSALF YGYYNNQRTI GWLRYRLPMA YFMVGVSVFG YSLIIVIRSM
ASNTQGSTGE GESDNFTFSF KMFTSWDYLI GNSETADNKY ASITTSFKES IVDEQESNKE
ENIHLTRFLR VLANFLIICC LCGSGYLIYF VVKRSQQFSK MQNVSWYERN EVEIVMSLLG
MFCPPLFETI AALENYHPRT GLKWQLGRIF ALFLGNLYTF LLALMDDVHL KLANEETIKN
ITHWTLFNYY NSSGWNESVP RPPLHPADVP RGSCWETAVG IEFMRLTVSD MLVTYITILL
GDFLRACFVR FMNYCWCWDL EAGFPSYAEF DISGNVLGLI FNQGMIWMGS FYAPGLVGIN
VLRLLTSMYF QCWAVMSSNV PHERVFKASR SNNFYMGLLL LVLFLSLLPV AYTIMSLPPS
FDCGPFSGKN RMYDVLQETI ENDFPTFLGK IFAFLANPGL IIPAILLMFL AIYYLNSVSK
SLSRANAQLR KKIQVLREVE KSHKSVKGKA TARDSEDTPK SSSKNATQLQ LTKEETTPPS
ASQSQAMDKK AQGPGTSNSA SRTTLPASGH LPISRPPGIG PDSGHAPSQT HPWRSASGKS
AQRPPH
