ID   CLRN2_HUMAN             Reviewed;         232 AA.
AC   A0PK11;
DT   06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 1.
DT   03-AUG-2022, entry version 94.
DE   RecName: Full=Clarin-2;
GN   Name=CLRN2 {ECO:0000312|HGNC:HGNC:33939};
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   INVOLVEMENT IN DFNB117, AND VARIANT DFNB117 LYS-165.
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:0000250|UniProtKB:B2RVW2}.
CC   -!- INTERACTION:
CC       A0PK11; Q8N6S5: ARL6IP6; NbExp=3; IntAct=EBI-12813623, EBI-2808844;
CC       A0PK11; O00501: CLDN5; NbExp=3; IntAct=EBI-12813623, EBI-18400628;
CC       A0PK11; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-12813623, EBI-11749983;
CC       A0PK11; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-12813623, EBI-12142257;
CC       A0PK11; P26715: KLRC1; NbExp=3; IntAct=EBI-12813623, EBI-9018187;
CC       A0PK11; Q8N386: LRRC25; NbExp=3; IntAct=EBI-12813623, EBI-11304917;
CC       A0PK11; O14524-2: NEMP1; NbExp=3; IntAct=EBI-12813623, EBI-10969203;
CC       A0PK11; Q9Y3P8: SIT1; NbExp=3; IntAct=EBI-12813623, EBI-6977215;
CC       A0PK11; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-12813623, EBI-17280858;
CC       A0PK11; P27105: STOM; NbExp=3; IntAct=EBI-12813623, EBI-1211440;
CC       A0PK11; Q8N6K0: TEX29; NbExp=3; IntAct=EBI-12813623, EBI-19027521;
CC       A0PK11; Q9H7M9: VSIR; NbExp=3; IntAct=EBI-12813623, EBI-744988;
CC   -!- SUBCELLULAR LOCATION: Cell projection, stereocilium membrane
CC       {ECO:0000250|UniProtKB:B2RVW2}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- DISEASE: Deafness, autosomal recessive, 117 (DFNB117) [MIM:619174]: A
CC       form of non-syndromic deafness characterized by pre-lingual, moderate-
CC       to-profound sensorineural hearing loss. Sensorineural hearing loss
CC       results from damage to the neural receptors of the inner ear, the nerve
CC       pathways to the brain, or the area of the brain that receives sound
CC       information. {ECO:0000269|PubMed:33496845}. Note=The disease is caused
CC       by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the clarin family. {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; AC093600; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC127863; AAI27864.1; -; mRNA.
DR   CCDS; CCDS47032.1; -.
DR   RefSeq; NP_001073296.1; NM_001079827.2.
DR   AlphaFoldDB; A0PK11; -.
DR   BioGRID; 570156; 76.
DR   IntAct; A0PK11; 12.
DR   STRING; 9606.ENSP00000424711; -.
DR   TCDB; 9.A.46.1.2; the clarin (clrn) family.
DR   GlyGen; A0PK11; 1 site.
DR   BioMuta; CLRN2; -.
DR   MassIVE; A0PK11; -.
DR   PaxDb; A0PK11; -.
DR   PeptideAtlas; A0PK11; -.
DR   PRIDE; A0PK11; -.
DR   Antibodypedia; 51092; 42 antibodies from 13 providers.
DR   DNASU; 645104; -.
DR   Ensembl; ENST00000511148.2; ENSP00000424711.2; ENSG00000249581.2.
DR   GeneID; 645104; -.
DR   KEGG; hsa:645104; -.
DR   MANE-Select; ENST00000511148.2; ENSP00000424711.2; NM_001079827.2; NP_001073296.1.
DR   UCSC; uc003gpg.1; human.
DR   CTD; 645104; -.
DR   DisGeNET; 645104; -.
DR   GeneCards; CLRN2; -.
DR   HGNC; HGNC:33939; CLRN2.
DR   HPA; ENSG00000249581; Not detected.
DR   MalaCards; CLRN2; -.
DR   MIM; 618988; gene.
DR   MIM; 619174; phenotype.
DR   neXtProt; NX_A0PK11; -.
DR   OpenTargets; ENSG00000249581; -.
DR   PharmGKB; PA162382499; -.
DR   VEuPathDB; HostDB:ENSG00000249581; -.
DR   eggNOG; ENOG502QUCR; Eukaryota.
DR   GeneTree; ENSGT00850000132319; -.
DR   HOGENOM; CLU_095723_1_0_1; -.
DR   InParanoid; A0PK11; -.
DR   OMA; CFWICVA; -.
DR   OrthoDB; 1188976at2759; -.
DR   PhylomeDB; A0PK11; -.
DR   TreeFam; TF331875; -.
DR   PathwayCommons; A0PK11; -.
DR   SignaLink; A0PK11; -.
DR   BioGRID-ORCS; 645104; 5 hits in 1059 CRISPR screens.
DR   GenomeRNAi; 645104; -.
DR   Pharos; A0PK11; Tdark.
DR   PRO; PR:A0PK11; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; A0PK11; protein.
DR   Bgee; ENSG00000249581; Expressed in cortical plate and 16 other tissues.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0032421; C:stereocilium bundle; ISS:UniProtKB.
DR   GO; GO:0060171; C:stereocilium membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0060088; P:auditory receptor cell stereocilium organization; ISS:UniProtKB.
DR   GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR   GO; GO:0120045; P:stereocilium maintenance; ISS:UniProtKB.
DR   InterPro; IPR026748; Clarin.
DR   PANTHER; PTHR31548; PTHR31548; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Deafness; Disease variant; Glycoprotein;
KW   Hearing; Membrane; Non-syndromic deafness; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..232
FT                   /note="Clarin-2"
FT                   /id="PRO_0000274697"
FT   TRANSMEM        10..30
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"
FT   CARBOHYD        48
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         113
FT                   /note="L -> V (in dbSNP:rs13147559)"
FT                   /id="VAR_053826"
FT   VARIANT         153
FT                   /note="A -> T (in dbSNP:rs2597791)"
FT                   /id="VAR_053827"
FT   VARIANT         165
FT                   /note="T -> K (in DFNB117; due to a nucleotide substitution
FT                   that can result in aberrant splicing; patient cells contain
FT                   both normally spliced transcripts and transcripts that
FT                   retained intron 2)"
FT                   /evidence="ECO:0000269|PubMed:33496845"
FT                   /id="VAR_085237"
SQ   SEQUENCE   232 AA;  25446 MW;  B6521162BA9B14A6 CRC64;
     MPGWFKKAWY GLASLLSFSS FILIIVALVV PHWLSGKILC QTGVDLVNAT DRELVKFIGD
     IYYGLFRGCK VRQCGLGGRQ SQFTIFPHLV KELNAGLHVM ILLLLFLALA LALVSMGFAI
     LNMIQVPYRA VSGPGGICLW NVLAGGVVAL AIASFVAAVK FHDLTERIAN FQEKLFQFVV
     VEEQYEESFW ICVASASAHA ANLVVVAISQ IPLPEIKTKI EEATVTAEDI LY