TMC2A_DANRE
ID TMC2A_DANRE Reviewed; 916 AA.
AC E7FFT2; A0A076V364; A2BHH3;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Transmembrane channel-like protein 2-A {ECO:0000303|PubMed:25114259};
GN Name=tmc2a {ECO:0000303|PubMed:25114259};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PCDH15A, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND PHYLOGENETIC
RP ANALYSIS.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Probable ion channel required for the normal function of hair
CC cells (By similarity). Component of the hair cell's mechanotransduction
CC (MET) machinery. Involved in mechanosensitive responses of the hair
CC cells (PubMed:25114259). {ECO:0000250|UniProtKB:Q8TDI7,
CC ECO:0000269|PubMed:25114259}.
CC -!- SUBUNIT: Interacts (via N-terminus) with both isoforms CD1 and CD3 of
CC PCDH15A (via cytoplasmic domain); this interaction is required for
CC mechanotransduction of the hair cells and correct localization of
CC PCDH15A in hair bundles of the hair cells.
CC {ECO:0000269|PubMed:25114259}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25114259};
CC Multi-pass membrane protein {ECO:0000255|RuleBase:RU310713}.
CC Note=Localized to mature hair bundles of the hair cells.
CC {ECO:0000269|PubMed:25114259}.
CC -!- TISSUE SPECIFICITY: In adults, expression is restricted to the hair
CC cells of inner ear and lateral line organ. Expressed at higher levels
CC in the larval inner ear than in the lateral-line neuromasts.
CC {ECO:0000269|PubMed:25114259}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the nascent hair cells of the
CC developing ear as early as 1 day post fertilization (dpf), and
CC expression in the inner ear continues throughout development.
CC Expression is restricted to the upper hair cell layer of the
CC neuroepithelium at 5 dpf. {ECO:0000269|PubMed:25114259}.
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000255|RuleBase:RU310713}.
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DR EMBL; KM115407; AIK19896.1; -; mRNA.
DR EMBL; BX571945; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX950207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001289166.1; NM_001302237.1.
DR AlphaFoldDB; E7FFT2; -.
DR SMR; E7FFT2; -.
DR STRING; 7955.ENSDARP00000117851; -.
DR TCDB; 1.A.17.4.13; the calcium-dependent chloride channel (ca-clc) family.
DR PaxDb; E7FFT2; -.
DR Ensembl; ENSDART00000073638; ENSDARP00000068128; ENSDARG00000033104.
DR GeneID; 571240; -.
DR KEGG; dre:571240; -.
DR CTD; 571240; -.
DR eggNOG; ENOG502QVCF; Eukaryota.
DR GeneTree; ENSGT01050000244942; -.
DR HOGENOM; CLU_013958_2_0_1; -.
DR OrthoDB; 310839at2759; -.
DR TreeFam; TF313462; -.
DR PRO; PR:E7FFT2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IBA:GO_Central.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IBA:GO_Central.
DR GO; GO:0060119; P:inner ear receptor cell development; IEP:UniProtKB.
DR GO; GO:0048882; P:lateral line development; IEP:UniProtKB.
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 1: Evidence at protein level;
KW Cell membrane; Ion channel; Ion transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..916
FT /note="Transmembrane channel-like protein 2-A"
FT /id="PRO_0000441915"
FT TOPO_DOM 1..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..344
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 345..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..478
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 479..499
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 517..537
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 538..649
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 650..670
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 671..704
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 705..725
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 726..762
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 763..783
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 784..916
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..916
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..110
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..146
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 804..825
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 916 AA; 103312 MW; 8C710B1150880FE0 CRC64;
MPKKSDTTRK LEDVGIEIDG DVDSAEEDKK SKGKGGKKAA GGKRGKASED GEDEDEDDKP
PKGRRAANKK KPAPVDEEDS DDDIPQRRSA GNRRRGNVRE RGDGDKKKSG KKGRRGGKKN
EKGKGKDSDK DSDKDEKKKK NSSGDESDSD EEDESMSEGE MAKLMEEVEE KKKLIANIRN
KPWRMRRRLK VLKEAQQFVD KFEGALGKGK GRKLYAYKVM MMKKWIKFKR DFENFRTACI
PWERKIKEVE SHFGSSVASY FIFLRWMYGM NLVLFSLTFG LVVIPEVLMG LPYGSIPRKT
VPREDQDTAM DYSVLTDFNG YCKYSVLFYG YYNNQRTIGF LKFRLPLSYL MVGIGTFGYS
LMVVIRTMAK NADVGGGDGE DNEFTFAWKM FTSWDYLIGN AETADNKYAS ITTSFKESIV
DEQENQKDEN IHLRRFLRVL ANFLITCTLG GSGYLIYFVV KRSQEFQNMD NLSWYEKNEL
EIIMSLLGLV GPMLFETIAE LEEYHPRIAL KWQLGRIFAL FLGNLYTFLL ALFDEVNAKL
EEEESIKNAS IWFLKEYYAN YTANNPNDTG TPPPINPADA IRGPCWETTV GVEFVKLTIS
DIQVTYLTIL IGDFLRAFIV RFLNYCWCWD LEAGWPSYGE FDISGNVLGL VFNQGMIWMG
AFYAPGLVGI NVLRLLSSMY YQCWAVMACN VPHERVFKAS KSNNFYMGLL LLILFLSLLP
VVYTIMSLPP SFDCGPFSGK ERMFDVVMET IDLDLPAFMG TLFGYVANPG LVISAVLLMV
LAIYYLNSVS EAYKNSNNEL KKKMQMARDE EKNRRNNKDS TNQVMKDLED LLPNRPPTPP
SPRENIAEKN QGQGGKSAKV KPGTAGGVHL QKDVSLASAN PNARGPVTRA PGPRGPGPLP
GQPGAGRGQG PPPRRQ
