TMC2_MOUSE
ID TMC2_MOUSE Reviewed; 888 AA.
AC Q8R4P4; Q7TQB1;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Transmembrane channel-like protein 2;
DE AltName: Full=Transmembrane cochlear-expressed protein 2;
GN Name=Tmc2;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 NUCLEOTIDE SEQUENCE [MRNA] OF 505-643, 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 [3]
RP INTERACTION WITH PCDH15.
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 [4]
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).
CC -!- FUNCTION: Probable ion channel required for the normal function of
CC cochlear hair cells (By similarity). 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:0000250|UniProtKB:Q8TDI7}.
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 (PubMed:28504928). Interacts (via N-terminus) with both
CC isoforms CD1 and CD3 of PCDH15 (PubMed:25114259).
CC {ECO:0000269|PubMed:25114259, ECO:0000269|PubMed:28504928}.
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:0000269|PubMed:28504928}.
CC -!- TISSUE SPECIFICITY: Inner ear and testis. {ECO:0000269|PubMed:11850618,
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. {ECO:0000269|PubMed:11850618}.
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}.
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DR EMBL; AF417581; AAL86402.1; -; mRNA.
DR EMBL; AY263156; AAP35264.1; -; mRNA.
DR CCDS; CCDS16736.1; -.
DR RefSeq; NP_619596.1; NM_138655.1.
DR AlphaFoldDB; Q8R4P4; -.
DR SMR; Q8R4P4; -.
DR STRING; 10090.ENSMUSP00000077139; -.
DR TCDB; 1.A.17.4.1; the calcium-dependent chloride channel (ca-clc) family.
DR iPTMnet; Q8R4P4; -.
DR PhosphoSitePlus; Q8R4P4; -.
DR PaxDb; Q8R4P4; -.
DR PRIDE; Q8R4P4; -.
DR Antibodypedia; 23203; 64 antibodies from 16 providers.
DR DNASU; 192140; -.
DR Ensembl; ENSMUST00000077988; ENSMUSP00000077139; ENSMUSG00000060332.
DR Ensembl; ENSMUST00000166774; ENSMUSP00000125843; ENSMUSG00000060332.
DR GeneID; 192140; -.
DR KEGG; mmu:192140; -.
DR UCSC; uc008mik.1; mouse.
DR CTD; 117532; -.
DR MGI; MGI:2151017; Tmc2.
DR VEuPathDB; HostDB:ENSMUSG00000060332; -.
DR eggNOG; ENOG502QVCF; Eukaryota.
DR GeneTree; ENSGT01050000244942; -.
DR HOGENOM; CLU_013958_2_0_1; -.
DR InParanoid; Q8R4P4; -.
DR OMA; HAPSQTH; -.
DR OrthoDB; 310839at2759; -.
DR PhylomeDB; Q8R4P4; -.
DR TreeFam; TF313462; -.
DR BioGRID-ORCS; 192140; 3 hits in 71 CRISPR screens.
DR PRO; PR:Q8R4P4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R4P4; protein.
DR Bgee; ENSMUSG00000060332; Expressed in crista ampullaris and 11 other tissues.
DR Genevisible; Q8R4P4; MM.
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; IGI:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; 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; IGI:MGI.
DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IGI:MGI.
DR GO; GO:0060005; P:vestibular reflex; IGI: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 Cell membrane; Ion channel; Ion transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..888
FT /note="Transmembrane channel-like protein 2"
FT /id="PRO_0000185383"
FT TOPO_DOM 1..245
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..318
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 434..490
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 491..511
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 512..675
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 676..696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 697..732
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 733..753
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 754..888
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 813..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..62
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 813..855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 862..881
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 888 AA; 101134 MW; 6D834D7987768FA7 CRC64;
MSPQLKSLDE EGDKSARRPT RKQTSRAACP QDGHRAQSSR KDPAKGSPRP GSSRKKQMEH
GSYHKGLQGQ KPRKVERSLQ GRKKDRRTSL KEQRASPKKE REALRKEAGK QLRKPRSTSL
GSSVSTGDSL SEEELAQILE QVEEKKKLIT TVRNKPWPMA KKLRELREAQ AFVEKYEGAL
GKGKGKHLYA YRMMMAKKWV KFKRDFDNFK TQCIPWEMKI KDIESHFGSS VASYFIFLRW
MYGVNLVLFG LIFGLVIIPE VLMGMPYGSI PRKTVPRAEE ERAMDFSVLW DFEGYIKYSA
LFYGYYNNQR TIGWLRYRLP MAYFMVGVSV FGYSLMIVIR SMASNTQGST SEGDSDSFTF
SFKMFTSWDY LIGNSETADN KYVSITTSFK ESIVDEQESN KEGNIHLTRF LRVLANFLIL
CCLCGSGYLI YFVVKRSQEF SKMQNVSWYE RNEVEIVMSL LGMFCPPLFE TIAALENYHP
RTGLKWQLGR IFALFLGNLY TFLLALMDDV HLKLSNEEKI KNITHWTLFN YYNSSGGNES
VPRPPPHPAD VPRGSCWETA VGIEFMRLTV SDMLVTYLTI LVGDFLRACF VRFMNHCWCW
DLEAGFPSYA EFDISGNVLG LIFNQGMIWM GSFYAPGLVG INVLRLLTSM YFQCWAVMSS
NVPHERVFKA SRSNNFYMGL LLLVLFLSLL PVAYTVMSLP PSFDCGPFSG KNRMYDVLHE
TIENDFPKFL GKIFAFLANP GLIIPAILLM FLAIYYLNSV SKSLSRANAQ LRKKIQALRE
VEKNHKSIKG KAIVTYSEDT IKNSSKNATQ IHLTKEEPTS HSSSQIQTLD KKAQGPHTSS
TEGGASPSTS WHHVGSQPPR GRRDSGQPQS QTYTGRSPSG KRTQRPHN
