ID   CLRN2_DANRE             Reviewed;         233 AA.
AC   A0A2R8RY99;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   20-JUN-2018, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Clarin-2;
GN   Name=clrn2 {ECO:0000312|ZFIN:ZDB-GENE-061207-64};
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 [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).
RN   [2]
RP   DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP   FUNCTION.
RX   PubMed=33496845; DOI=10.1007/s00439-020-02254-z;
RA   Vona B., Mazaheri N., Lin S.J., Dunbar L.A., Maroofian R., Azaiez H.,
RA   Booth K.T., Vitry S., Rad A., Rueschendorf F., Varshney P., Fowler B.,
RA   Beetz C., Alagramam K.N., Murphy D., Shariati G., Sedaghat A., Houlden H.,
RA   Petree C., VijayKumar S., Smith R.J.H., Haaf T., El-Amraoui A., Bowl M.R.,
RA   Varshney G.K., Galehdari H.;
RT   "A biallelic variant in CLRN2 causes non-syndromic hearing loss in
RT   humans.";
RL   Hum. Genet. 140:915-931(2021).
CC   -!- FUNCTION: Plays a key role to hearing function. Required for normal
CC       organization and maintenance of the stereocilia bundle.
CC       {ECO:0000269|PubMed:33496845}.
CC   -!- SUBCELLULAR LOCATION: Cell projection, stereocilium membrane
CC       {ECO:0000250|UniProtKB:B2RVW2}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: High expression in utricle, saccule and lagena of
CC       the inner ear. Expression is restricted to hair cells.
CC       {ECO:0000269|PubMed:33496845}.
CC   -!- DEVELOPMENTAL STAGE: First detected at 18 hours post fertilization
CC       (hpf), a stage when the otic placode begins to form the otic vesicle in
CC       zebrafish, and then increases throughout development.
CC       {ECO:0000269|PubMed:33496845}.
CC   -!- DISRUPTION PHENOTYPE: Depletion of clrn2 using CRISPR-Cas9-mediated
CC       gene editing induces reduced response after sound stimulation.
CC       Furthermore, clrn2 crispants show disrupted hair bundle structure and
CC       fewer hair cells compared to controls. {ECO:0000269|PubMed:33496845}.
CC   -!- SIMILARITY: Belongs to the clarin family. {ECO:0000305}.
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DR   EMBL; BX548248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; A0A2R8RY99; -.
DR   Ensembl; ENSDART00000189585; ENSDARP00000155872; ENSDARG00000110932.
DR   ZFIN; ZDB-GENE-061207-64; clrn2.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Unplaced.
DR   GO; GO:0070451; C:cell hair; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0060171; C:stereocilium membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:UniProtKB.
DR   GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR   InterPro; IPR026748; Clarin.
DR   PANTHER; PTHR31548; PTHR31548; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cell projection; Hearing; Membrane; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..233
FT                   /note="Clarin-2"
FT                   /id="PRO_0000454160"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        100..120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        187..207
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   233 AA;  25835 MW;  5B7E2C2BFEB7647F CRC64;
     MPTLWKQIVF SFASILSIGS VVLLVVALST ERWVTGTTLC QTGVDLVNAS RPELEQFTGH
     IYYGLFQGGK TRRCGLGIRR AKIYIFPKLI KKINSGLHMI IIFFLFTAIG FAVVSLAFCI
     YNARKVPYQS IKGPFGLYIW NFIAGKSIAM GFACFLAAIQ CHKLTEHVAN YSESLFTLVI
     LEENLGFSFW LVVASAVTHG ANILVVASSK IHLPKIQTKK PEEPTATGED FLY