CLRN2_MOUSE
ID CLRN2_MOUSE Reviewed; 232 AA.
AC B2RVW2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Clarin-2;
GN Name=Clrn2 {ECO:0000312|MGI:MGI:3646230};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=31448880; DOI=10.15252/emmm.201910288;
RA Dunbar L.A., Patni P., Aguilar C., Mburu P., Corns L., Wells H.R.,
RA Delmaghani S., Parker A., Johnson S., Williams D., Esapa C.T., Simon M.M.,
RA Chessum L., Newton S., Dorning J., Jeyarajan P., Morse S., Lelli A.,
RA Codner G.F., Peineau T., Gopal S.R., Alagramam K.N., Hertzano R., Dulon D.,
RA Wells S., Williams F.M., Petit C., Dawson S.J., Brown S.D., Marcotti W.,
RA El-Amraoui A., Bowl M.R.;
RT "Clarin-2 is essential for hearing by maintaining stereocilia integrity and
RT function.";
RL EMBO Mol. Med. 11:e10288-e10288(2019).
RN [4]
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 and for mechano-
CC electrical transduction. {ECO:0000269|PubMed:31448880,
CC ECO:0000269|PubMed:33496845}.
CC -!- SUBCELLULAR LOCATION: Cell projection, stereocilium membrane
CC {ECO:0000269|PubMed:31448880}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Detected in inner ear, particularly in hair bundles
CC of auditory hair cells and is enriched in apical stereocilia. Detected
CC in eye, but not in brain or muscle. {ECO:0000269|PubMed:31448880}.
CC -!- DEVELOPMENTAL STAGE: Expression in the cochlea is stable from late
CC embryonic stages to P12 (the onset of hearing in mice), but thereafter
CC increases. {ECO:0000269|PubMed:31448880}.
CC -!- DISRUPTION PHENOTYPE: Mice homozygous for an ENU-induced allele exhibit
CC an early-onset, progressive hearing loss, with a lack of fast-graded
CC voltage responses. These mice harbor an early truncating nonsense
CC variant (Trp4Ter). By postnatal days 6 (P6), mutants do not exhibit any
CC gross patterning defects, or differences in the overall number of outer
CC hair cells (OHC) and inner hair cells (IHC) bundles compared to
CC controls. However, despite normal shape organization, these mice shown
CC a progressive reduction in height of the middle and shortest row
CC stereocilia, which is evident first in OHCs by P8, and then later in
CC IHCs at P16. {ECO:0000269|PubMed:31448880}.
CC -!- SIMILARITY: Belongs to the clarin family. {ECO:0000305}.
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DR EMBL; GL456117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC147370; AAI47371.1; -; mRNA.
DR EMBL; BC147371; AAI47372.1; -; mRNA.
DR EMBL; BC147726; AAI47727.1; -; mRNA.
DR EMBL; BC147731; AAI47732.1; -; mRNA.
DR CCDS; CCDS51497.1; -.
DR RefSeq; NP_001156789.1; NM_001163317.1.
DR AlphaFoldDB; B2RVW2; -.
DR STRING; 10090.ENSMUSP00000058204; -.
DR PaxDb; B2RVW2; -.
DR PeptideAtlas; B2RVW2; -.
DR PRIDE; B2RVW2; -.
DR Antibodypedia; 51092; 42 antibodies from 13 providers.
DR Ensembl; ENSMUST00000053250; ENSMUSP00000058204; ENSMUSG00000049530.
DR GeneID; 624224; -.
DR KEGG; mmu:624224; -.
DR UCSC; uc012dvy.1; mouse.
DR CTD; 645104; -.
DR MGI; MGI:3646230; Clrn2.
DR VEuPathDB; HostDB:ENSMUSG00000049530; -.
DR eggNOG; ENOG502QUCR; Eukaryota.
DR GeneTree; ENSGT00850000132319; -.
DR HOGENOM; CLU_095723_1_0_1; -.
DR InParanoid; B2RVW2; -.
DR OMA; CFWICVA; -.
DR OrthoDB; 1188976at2759; -.
DR PhylomeDB; B2RVW2; -.
DR TreeFam; TF331875; -.
DR BioGRID-ORCS; 624224; 1 hit in 71 CRISPR screens.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; B2RVW2; protein.
DR Bgee; ENSMUSG00000049530; Expressed in hippocampal formation and 3 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI.
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:0042491; P:inner ear auditory receptor cell differentiation; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0120045; P:stereocilium maintenance; 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..232
FT /note="Clarin-2"
FT /id="PRO_0000454159"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..121
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 232 AA; 25486 MW; DFC0853F77C8545A CRC64;
MPGWFKKVWY GLASLLSFSS FLLIIVALSL PHWLSGKILC QTGVDLVNAT DPELVKFIGD
IYYGLFRGCK VRQCGLGGRQ SQFTIFPHLV KELNAGLHVT ILLLLFLALA LALVSMGFAI
LNIIQVPYRA VNGPGGICLW NVLAGGVVAL AIGSFMAAVK FHDLTERIAN FQERLFQFVV
VEEQYEESFW ICVASASAHA ANLVVVAISQ IPLPEIKTKM EEATVTPEDI LY
