ID PCD15_HUMAN Reviewed; 1955 AA. AC Q96QU1; A6NL19; C6ZEF5; C6ZEF6; C6ZEF7; Q5VY38; Q5VY39; Q6TRH8; Q8NDB9; AC Q96QT8; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=Protocadherin-15; DE Flags: Precursor; GN Name=PCDH15; Synonyms=USH1F; 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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INVOLVEMENT IN RP USHER SYNDROME TYPE 1F, AND VARIANT GLN-929. RC TISSUE=Fetal brain; RX PubMed=11487575; DOI=10.1093/hmg/10.16.1709; RA Alagramam K.N., Yuan H., Kuehn M.H., Murcia C.L., Wayne S., RA Srisailpathy C.R.S., Lowry R.B., Knaus R., Van Laer L., Bernier F.P., RA Schwartz S., Lee C., Morton C.C., Mullins R.F., Ramesh A., Van Camp G., RA Hagemen G.S., Woychik R.P., Smith R.J.H.; RT "Mutations in the novel protocadherin PCDH15 cause Usher syndrome type RT 1F."; RL Hum. Mol. Genet. 10:1709-1718(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN USHER SYNDROME RP TYPE 1F. RX PubMed=11398101; DOI=10.1086/321277; RA Ahmed Z.M., Riazuddin S., Bernstein S.L., Ahmed Z., Khan S., Griffith A.J., RA Morell R.J., Friedman T.B., Riazuddin S., Wilcox E.R.; RT "Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F."; RL Am. J. Hum. Genet. 69:25-34(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS DFNB23 GLY-134 AND RP ASP-262. RX PubMed=14570705; DOI=10.1093/hmg/ddg358; RA Ahmed Z.M., Riazuddin S., Ahmad J., Bernstein S.L., Guo Y., Sabar M.F., RA Sieving P., Riazuddin S., Griffith A.J., Friedman T.B., Belyantseva I.A., RA Wilcox E.R.; RT "PCDH15 is expressed in the neurosensory epithelium of the eye and ear and RT mutant alleles are responsible for both USH1F and DFNB23."; RL Hum. Mol. Genet. 12:3215-3223(2003). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), TISSUE SPECIFICITY, VARIANT RP DFNB23 GLY-134, AND VARIANT USH1DF GLY-178. RC TISSUE=Retina; RX PubMed=18719945; DOI=10.1007/s00439-008-0543-3; RA Ahmed Z.M., Riazuddin S., Aye S., Ali R.A., Venselaar H., Anwar S., RA Belyantseva P.P., Qasim M., Riazuddin S., Friedman T.B.; RT "Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 RT and type 1 Usher syndrome."; RL Hum. Genet. 124:215-223(2008). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS ALA-435 RP AND GLN-929. RC TISSUE=Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP IDENTIFICATION OF ISOFORMS 1 AND 3, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND VARIANT ALA-19. RX PubMed=16369489; DOI=10.1038/sj.onc.1209301; RA Rouget-Quermalet V., Giustiniani J., Marie-Cardine A., Beaud G., RA Besnard F., Loyaux D., Ferrara P., Leroy K., Shimizu N., Gaulard P., RA Bensussan A., Schmitt C.; RT "Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker RT for NK/T cell lymphomas."; RL Oncogene 25:2807-2811(2006). RN [8] RP VARIANTS USH1F LYS-1342 AND THR-1867 DEL. RX PubMed=15660226; DOI=10.1007/s00439-004-1227-2; RA Ouyang X.M., Yan D., Du L.L., Hejtmancik J.F., Jacobson S.G., Nance W.E., RA Li A.R., Angeli S., Kaiser M., Newton V., Brown S.D.M., Balkany T., RA Liu X.Z.; RT "Characterization of Usher syndrome type I gene mutations in an Usher RT syndrome patient population."; RL Hum. Genet. 116:292-299(2005). RN [9] RP INVOLVEMENT IN USH1DF. RX PubMed=15537665; DOI=10.1093/hmg/ddi010; RA Zheng Q.Y., Yan D., Ouyang X.M., Du L.L., Yu H., Chang B., Johnson K.R., RA Liu X.Z.; RT "Digenic inheritance of deafness caused by mutations in genes encoding RT cadherin 23 and protocadherin 15 in mice and humans."; RL Hum. Mol. Genet. 14:103-111(2005). RN [10] RP VARIANTS USH1F GLN-134 AND ALA-1161 (ISOFORM 4), AND VARIANTS ALA-19; RP SER-174; SER-380; ALA-435; GLN-929 AND SER-1273. RX PubMed=22815625; RA Jaijo T., Oshima A., Aller E., Carney C., Usami S., Millan J.M., RA Kimberling W.J.; RT "Mutation screening of the PCDH15 gene in Spanish patients with Usher RT syndrome type I."; RL Mol. Vis. 18:1719-1726(2012). RN [11] RP VARIANT DFNB23 1576-GLN--LEU-1955 DEL. RX PubMed=28281779; DOI=10.1089/gtmb.2016.0328; RA Wang R., Han S., Khan A., Zhang X.; RT "Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or RT Syndromic Hearing Loss."; RL Genet. Test. Mol. Biomarkers 21:316-321(2017). CC -!- FUNCTION: Calcium-dependent cell-adhesion protein. Essential for CC maintenance of normal retinal and cochlear function. CC -!- SUBUNIT: Antiparallel heterodimer with CDH23. Found in a complex with CC TMIE and LHFPL5. Interacts with LHFPL5/TMHS; this interaction is CC required for efficient localization to hair bundles. Interacts with CC MYO7A. Interacts with USH1G; this interaction may recruit USH1G to the CC plasma membrane. Interacts with TOMT. Isoforms CD1 and CD3 interact CC with TMC1 (via N-terminus) and TMC2 (via N-terminus). CC {ECO:0000250|UniProtKB:Q99PJ1}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I CC membrane protein {ECO:0000250}. Note=Efficient localization to the CC plasma membrane requires the presence of LHFPL5. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=A, CD1-1; CC IsoId=Q96QU1-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q96QU1-2; Sequence=VSP_028257, VSP_028258; CC Name=3; Synonyms=C; CC IsoId=Q96QU1-3; Sequence=VSP_028259, VSP_028260; CC Name=4; Synonyms=CD2-1; CC IsoId=Q96QU1-4; Sequence=VSP_046616, VSP_046617, VSP_046622; CC Name=5; Synonyms=CD3-1; CC IsoId=Q96QU1-6; Sequence=VSP_046618, VSP_046621; CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, kidney, spleen and CC testis. Found also in the inner and outer synaptic layers, and the CC nerve fiber layer in adult and fetal retinas. Found in the supporting CC cells, outer sulcus cells and spiral ganglion of fetal cochlea. CC Expressed in cytotoxic tumor-derived T- and NK-cell lines as well as CC biopsies of nasal NK/T-cell lymphomas. Not detected in normal or in CC vitro activated peripheral blood cells, CD4 or CD8 lymphocytes or NK CC cells. Isoform 3 is expressed in brain, heart, cerebellum and kidney. CC CD1 isoforms, such as isoform 1, have a limited pattern of expression CC and is detected in testis, retina and cochlea. CD2 isoforms, such as CC isoforms 4 and 5, are expressed in heart, kidney, thymus, spleen, CC testis, retina and cochlea. CD3 isoforms, such as isoform 6, are widely CC expressed. {ECO:0000269|PubMed:11487575, ECO:0000269|PubMed:16369489, CC ECO:0000269|PubMed:18719945}. CC -!- DOMAIN: Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic CC interaction with CDH23. {ECO:0000250}. CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each CC cadherin domain and rigidify the connections, imparting a strong CC curvature to the full-length ectodomain. {ECO:0000250}. CC -!- DISEASE: Usher syndrome 1F (USH1F) [MIM:602083]: USH is a genetically CC heterogeneous condition characterized by the association of retinitis CC pigmentosa with sensorineural deafness. Age at onset and differences in CC auditory and vestibular function distinguish Usher syndrome type 1 CC (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). CC USH1 is characterized by profound congenital sensorineural deafness, CC absent vestibular function and prepubertal onset of progressive CC retinitis pigmentosa leading to blindness. CC {ECO:0000269|PubMed:15660226, ECO:0000269|PubMed:22815625}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Usher syndrome 1D/F (USH1DF) [MIM:601067]: A digenic recessive CC form of Usher syndrome, a genetically heterogeneous condition CC characterized by the association of retinitis pigmentosa with CC sensorineural deafness. Age at onset and differences in auditory and CC vestibular function distinguish Usher syndrome type 1 (USH1), Usher CC syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is CC characterized by profound congenital sensorineural deafness, absent CC vestibular function and prepubertal onset of progressive retinitis CC pigmentosa leading to blindness. {ECO:0000269|PubMed:15537665, CC ECO:0000269|PubMed:18719945}. Note=The disease is caused by variants CC affecting distinct genetic loci, including the gene represented in this CC entry. CC -!- DISEASE: Deafness, autosomal recessive, 23 (DFNB23) [MIM:609533]: A CC form of non-syndromic sensorineural hearing loss. Sensorineural CC deafness results from damage to the neural receptors of the inner ear, CC the nerve pathways to the brain, or the area of the brain that receives CC sound information. {ECO:0000269|PubMed:14570705, CC ECO:0000269|PubMed:18719945, ECO:0000269|PubMed:28281779}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=ACF76477.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=CAD38850.2; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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; AY029205; AAK31581.1; -; mRNA. DR EMBL; AY029237; AAK31804.1; -; mRNA. DR EMBL; AY388963; AAR26468.1; -; mRNA. DR EMBL; EU718480; ACF76476.1; -; mRNA. DR EMBL; EU718481; ACF76477.1; ALT_SEQ; mRNA. DR EMBL; EU718482; ACF76478.1; -; mRNA. DR EMBL; AL834134; CAD38850.2; ALT_TERM; mRNA. DR EMBL; AC013737; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC016817; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC024073; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC027671; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353784; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356114; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL360214; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL365496; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS7248.1; -. [Q96QU1-1] DR CCDS; CCDS86093.1; -. [Q96QU1-3] DR CCDS; CCDS86094.1; -. [Q96QU1-6] DR CCDS; CCDS86095.1; -. [Q96QU1-4] DR RefSeq; NP_149045.3; NM_033056.3. [Q96QU1-1] DR RefSeq; XP_016872061.1; XM_017016572.1. DR PDB; 4XHZ; X-ray; 2.80 A; A=816-1144. DR PDB; 5T4M; X-ray; 2.24 A; A/B=263-616. DR PDB; 5T4N; X-ray; 2.70 A; A/B=263-616. DR PDB; 5ULY; X-ray; 2.64 A; A/B/C/D=143-390. DR PDB; 6E8F; X-ray; 2.99 A; A/B/C=263-608. DR PDB; 6EB5; X-ray; 2.60 A; A/B=143-390. DR PDB; 6MFO; X-ray; 3.15 A; A=27-391. DR PDB; 6N2E; X-ray; 2.90 A; A/B=27-391. DR PDBsum; 4XHZ; -. DR PDBsum; 5T4M; -. DR PDBsum; 5T4N; -. DR PDBsum; 5ULY; -. DR PDBsum; 6E8F; -. DR PDBsum; 6EB5; -. DR PDBsum; 6MFO; -. DR PDBsum; 6N2E; -. DR AlphaFoldDB; Q96QU1; -. DR SMR; Q96QU1; -. DR BioGRID; 122407; 2. DR IntAct; Q96QU1; 1. DR MINT; Q96QU1; -. DR STRING; 9606.ENSP00000363068; -. DR ChEMBL; CHEMBL6112; -. DR GlyCosmos; Q96QU1; 13 sites, No reported glycans. DR GlyGen; Q96QU1; 13 sites. DR iPTMnet; Q96QU1; -. DR PhosphoSitePlus; Q96QU1; -. DR BioMuta; PCDH15; -. DR DMDM; 116242702; -. DR EPD; Q96QU1; -. DR jPOST; Q96QU1; -. DR MassIVE; Q96QU1; -. DR MaxQB; Q96QU1; -. DR PaxDb; 9606-ENSP00000363068; -. DR PeptideAtlas; Q96QU1; -. DR ProteomicsDB; 77903; -. [Q96QU1-1] DR ProteomicsDB; 77904; -. [Q96QU1-2] DR ProteomicsDB; 77905; -. [Q96QU1-3] DR Antibodypedia; 27955; 115 antibodies from 20 providers. DR DNASU; 65217; -. DR Ensembl; ENST00000320301.11; ENSP00000322604.6; ENSG00000150275.20. [Q96QU1-1] DR Ensembl; ENST00000373955.5; ENSP00000363066.1; ENSG00000150275.20. [Q96QU1-3] DR Ensembl; ENST00000395445.6; ENSP00000378832.2; ENSG00000150275.20. [Q96QU1-4] DR Ensembl; ENST00000616114.4; ENSP00000483745.1; ENSG00000150275.20. [Q96QU1-6] DR GeneID; 65217; -. DR KEGG; hsa:65217; -. DR UCSC; uc001jju.2; human. [Q96QU1-1] DR AGR; HGNC:14674; -. DR CTD; 65217; -. DR DisGeNET; 65217; -. DR GeneCards; PCDH15; -. DR GeneReviews; PCDH15; -. DR HGNC; HGNC:14674; PCDH15. DR HPA; ENSG00000150275; Group enriched (adrenal gland, retina). DR MalaCards; PCDH15; -. DR MIM; 276900; phenotype. DR MIM; 601067; phenotype. DR MIM; 602083; phenotype. DR MIM; 605514; gene. DR MIM; 609533; phenotype. DR neXtProt; NX_Q96QU1; -. DR OpenTargets; ENSG00000150275; -. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR Orphanet; 231169; Usher syndrome type 1. DR PharmGKB; PA32999; -. DR VEuPathDB; HostDB:ENSG00000150275; -. DR eggNOG; KOG3594; Eukaryota. DR GeneTree; ENSGT00940000156675; -. DR HOGENOM; CLU_286776_0_0_1; -. DR InParanoid; Q96QU1; -. DR OrthoDB; 5353563at2759; -. DR PhylomeDB; Q96QU1; -. DR PathwayCommons; Q96QU1; -. DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea. DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea. DR SignaLink; Q96QU1; -. DR SIGNOR; Q96QU1; -. DR BioGRID-ORCS; 65217; 10 hits in 1140 CRISPR screens. DR ChiTaRS; PCDH15; human. DR GeneWiki; PCDH15; -. DR GenomeRNAi; 65217; -. DR Pharos; Q96QU1; Tbio. DR PRO; PR:Q96QU1; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q96QU1; Protein. DR Bgee; ENSG00000150275; Expressed in left adrenal gland cortex and 95 other cell types or tissues. DR ExpressionAtlas; Q96QU1; baseline and differential. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; IDA:HGNC-UCL. DR GO; GO:0001750; C:photoreceptor outer segment; IDA:HGNC-UCL. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032420; C:stereocilium; ISS:HGNC-UCL. DR GO; GO:0045202; C:synapse; IDA:HGNC-UCL. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0050957; P:equilibrioception; IMP:HGNC-UCL. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro. DR GO; GO:0048839; P:inner ear development; IEA:InterPro. DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:HGNC-UCL. DR GO; GO:0050953; P:sensory perception of light stimulus; IMP:HGNC-UCL. DR GO; GO:0007605; P:sensory perception of sound; IMP:HGNC-UCL. DR CDD; cd11304; Cadherin_repeat; 9. DR Gene3D; 2.60.40.3430; -; 1. DR Gene3D; 2.60.40.60; Cadherins; 10. DR InterPro; IPR002126; Cadherin-like_dom. DR InterPro; IPR015919; Cadherin-like_sf. DR InterPro; IPR020894; Cadherin_CS. DR InterPro; IPR041149; EC_dom. DR InterPro; IPR030718; EC_dom_sf. DR PANTHER; PTHR24025; DESMOGLEIN FAMILY MEMBER; 1. DR PANTHER; PTHR24025:SF30; NEURAL-CADHERIN; 1. DR Pfam; PF00028; Cadherin; 8. DR Pfam; PF18432; ECD; 1. DR PRINTS; PR00205; CADHERIN. DR PRINTS; PR01217; PRICHEXTENSN. DR SMART; SM00112; CA; 11. DR SUPFAM; SSF49313; Cadherin-like; 10. DR PROSITE; PS00232; CADHERIN_1; 3. DR PROSITE; PS50268; CADHERIN_2; 10. DR Genevisible; Q96QU1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell adhesion; Cell membrane; KW Deafness; Disease variant; Disulfide bond; Glycoprotein; Hearing; Membrane; KW Non-syndromic deafness; Reference proteome; Repeat; Retinitis pigmentosa; KW Secreted; Signal; Transmembrane; Transmembrane helix; Usher syndrome. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..1955 FT /note="Protocadherin-15" FT /id="PRO_0000003998" FT TOPO_DOM 27..1376 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1377..1397 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1398..1955 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 40..147 FT /note="Cadherin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 148..265 FT /note="Cadherin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 278..395 FT /note="Cadherin 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 396..509 FT /note="Cadherin 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 510..616 FT /note="Cadherin 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 617..717 FT /note="Cadherin 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 719..819 FT /note="Cadherin 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 820..926 FT /note="Cadherin 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 927..1035 FT /note="Cadherin 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 1037..1144 FT /note="Cadherin 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 1145..1259 FT /note="Cadherin 11" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT REGION 1426..1446 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1601..1623 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1745..1766 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1928..1955 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 52 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 201 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 419 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 559 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 662 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 724 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 768 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 821 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 851 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1064 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1084 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1175 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 32..120 FT /evidence="ECO:0000250" FT VAR_SEQ 1..1118 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14570705" FT /id="VSP_028257" FT VAR_SEQ 435 FT /note="D -> DVPPSGVP (in isoform 4)" FT /evidence="ECO:0000303|PubMed:18719945" FT /id="VSP_046616" FT VAR_SEQ 957..961 FT /note="GLPAS -> VSRRH (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_028259" FT VAR_SEQ 962..1955 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_028260" FT VAR_SEQ 1119..1125 FT /note="LRVPSKS -> MTFSHSG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14570705" FT /id="VSP_028258" FT VAR_SEQ 1456..1776 FT /note="ILFLLYHFQQSRGNNSVSEDRKHQQVVMPFSSNTIEAHKSAHVDGSLKSNKL FT KSARKFTFLSDEDDLSAHNPLYKENISQVSTNSDISQRTDFVDPFSPKIQAKSKSLRGP FT REKIQRLWSQSVSLPRRLMRKVPNRPEIIDLQQWQGTRQKAENENTGICTNKRGSSNPL FT LTTEEANLTEKEEIRQGETLMIEGTEQLKSLSSDSSFCFPRPHFSFSTLPTVSRTVELK FT SEPNVISSPAECSLELSPSRPCVLHSSLSRRETPICMLPIETERNIFENFAHPPNISPS FT ACPLPPPPPISPPSPPPAPAPLAPPPDISPFSL -> MYEMPQYGSRRRLLPPAGQEEY FT GEVVGEAEEEYEEEEEEPKKIKKPKVEIREPSEEEEVVVTIEKPPAAEPTYTTWKRARI FT FPMIFKKVRGLADKRGIVDLEGEEWQRRLEEEDKDYLKLTLDQEEATESTVESEEESSS FT DYTEYSEEESEFSESETTEEESESETPSEEEESSTPESEESESTESEGEKARKNIVLAR FT RRPMVEEVKEVKGRKEEPQEEQKEPKMEEEEHSEEEESGPAPVEESTDPEAQDIPEEGS FT AESASVEGGVESEEESESGSSSSSSESQSGGPWGYQVPAYDRSKNANQKKSPGANSEGY FT NTAL (in isoform 4)" FT /evidence="ECO:0000303|PubMed:18719945" FT /id="VSP_046617" FT VAR_SEQ 1456..1675 FT /note="ILFLLYHFQQSRGNNSVSEDRKHQQVVMPFSSNTIEAHKSAHVDGSLKSNKL FT KSARKFTFLSDEDDLSAHNPLYKENISQVSTNSDISQRTDFVDPFSPKIQAKSKSLRGP FT REKIQRLWSQSVSLPRRLMRKVPNRPEIIDLQQWQGTRQKAENENTGICTNKRGSSNPL FT LTTEEANLTEKEEIRQGETLMIEGTEQLKSLSSDSSFCFPRPHFSFSTLP -> MYEMP FT QYGSRRRLLPPAGQEEYGEVVGEAEEEYEEEEWARKRMIKLVVDREYETSSTGEDSAPE FT CQRNRLHHPSIHSNINGNIYIAQNGSVVRTRRACLTDNLKVASPVRLGGPFKKLDKLAV FT THEENVPLNTLSKGPFSTEKMNARPTLVTFAPCPVGTDNTAVKPLRNRLKSTVEQESMI FT DSKNIKEALEFHSDHTQSDDEELWMGPWNNLHIPMTKL (in isoform 5)" FT /evidence="ECO:0000303|PubMed:18719945" FT /id="VSP_046618" FT VAR_SEQ 1676..1955 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:18719945" FT /id="VSP_046621" FT VAR_SEQ 1777..1955 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:18719945" FT /id="VSP_046622" FT VARIANT 19 FT /note="S -> A (in dbSNP:rs11004439)" FT /evidence="ECO:0000269|PubMed:16369489, FT ECO:0000269|PubMed:22815625" FT /id="VAR_028289" FT VARIANT 134 FT /note="R -> G (in DFNB23; dbSNP:rs137853003)" FT /evidence="ECO:0000269|PubMed:14570705, FT ECO:0000269|PubMed:18719945" FT /id="VAR_024035" FT VARIANT 134 FT /note="R -> Q (in USH1F; dbSNP:rs767966376)" FT /evidence="ECO:0000269|PubMed:22815625" FT /id="VAR_071696" FT VARIANT 174 FT /note="N -> S (in dbSNP:rs145037203)" FT /evidence="ECO:0000269|PubMed:22815625" FT /id="VAR_071697" FT VARIANT 178 FT /note="D -> G (in USH1DF)" FT /evidence="ECO:0000269|PubMed:18719945" FT /id="VAR_069297" FT VARIANT 262 FT /note="G -> D (in DFNB23; dbSNP:rs137853002)" FT /evidence="ECO:0000269|PubMed:14570705" FT /id="VAR_024036" FT VARIANT 380 FT /note="G -> S (in dbSNP:rs10825269)" FT /evidence="ECO:0000269|PubMed:22815625" FT /id="VAR_028290" FT VARIANT 435 FT /note="D -> A (in dbSNP:rs4935502)" FT /evidence="ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:22815625" FT /id="VAR_028291" FT VARIANT 929 FT /note="R -> Q (in dbSNP:rs2135720)" FT /evidence="ECO:0000269|PubMed:11487575, FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:22815625" FT /id="VAR_028292" FT VARIANT 1273 FT /note="R -> S (in dbSNP:rs111033363)" FT /evidence="ECO:0000269|PubMed:22815625" FT /id="VAR_071698" FT VARIANT 1342 FT /note="Q -> K (in USH1F; benign; dbSNP:rs61731387)" FT /evidence="ECO:0000269|PubMed:15660226" FT /id="VAR_024037" FT VARIANT 1576..1955 FT /note="Missing (in DFNB23)" FT /evidence="ECO:0000269|PubMed:28281779" FT /id="VAR_079507" FT VARIANT 1867 FT /note="Missing (in USH1F)" FT /evidence="ECO:0000269|PubMed:15660226" FT /id="VAR_024038" FT CONFLICT 261 FT /note="L -> S (in Ref. 1; AAK31581)" FT /evidence="ECO:0000305" FT CONFLICT 467 FT /note="Q -> L (in Ref. 1; AAK31581)" FT /evidence="ECO:0000305" FT CONFLICT 1276 FT /note="Q -> R (in Ref. 1; AAK31581)" FT /evidence="ECO:0000305" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 40..47 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 55..58 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:6MFO" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 73..79 FT /evidence="ECO:0007829|PDB:6N2E" FT HELIX 81..83 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:6N2E" FT TURN 89..92 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:6N2E" FT TURN 107..109 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 113..122 FT /evidence="ECO:0007829|PDB:6N2E" FT TURN 123..125 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 128..138 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 146..150 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 152..157 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:6EB5" FT TURN 169..174 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:6EB5" FT HELIX 182..185 FT /evidence="ECO:0007829|PDB:6N2E" FT STRAND 187..192 FT /evidence="ECO:0007829|PDB:6EB5" FT HELIX 200..203 FT /evidence="ECO:0007829|PDB:6EB5" FT TURN 209..211 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:6EB5" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 227..236 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:5ULY" FT STRAND 247..257 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 264..266 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 281..287 FT /evidence="ECO:0007829|PDB:5T4M" FT HELIX 292..295 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 305..307 FT /evidence="ECO:0007829|PDB:6E8F" FT STRAND 309..311 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 313..315 FT /evidence="ECO:0007829|PDB:6EB5" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:6EB5" FT STRAND 322..331 FT /evidence="ECO:0007829|PDB:5T4M" FT HELIX 334..337 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 342..344 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 347..349 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 355..357 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 360..372 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 377..386 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 394..405 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 426..429 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 431..433 FT /evidence="ECO:0007829|PDB:6E8F" FT STRAND 442..447 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 449..451 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 456..461 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 463..467 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 471..473 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 476..484 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 493..500 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 512..519 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 527..530 FT /evidence="ECO:0007829|PDB:5T4M" FT HELIX 539..541 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 544..550 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 555..558 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 560..562 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 564..567 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 578..587 FT /evidence="ECO:0007829|PDB:5T4M" FT TURN 591..593 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 596..606 FT /evidence="ECO:0007829|PDB:5T4M" FT STRAND 818..829 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 837..840 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 846..848 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 853..856 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 859..861 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 862..864 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 865..867 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 869..871 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 873..878 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 882..884 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 891..899 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 908..917 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 924..927 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 929..935 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 944..947 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 950..952 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 959..961 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 964..968 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 973..978 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 979..981 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 983..985 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 987..992 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1001..1009 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1012..1014 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1017..1026 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 1029..1031 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1034..1036 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1038..1040 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1054..1057 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1067..1074 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1080..1082 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 1084..1086 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1088..1091 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 1097..1099 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1102..1111 FT /evidence="ECO:0007829|PDB:4XHZ" FT HELIX 1112..1115 FT /evidence="ECO:0007829|PDB:4XHZ" FT TURN 1116..1118 FT /evidence="ECO:0007829|PDB:4XHZ" FT STRAND 1127..1135 FT /evidence="ECO:0007829|PDB:4XHZ" FT VARIANT Q96QU1-4:1611 FT /note="E -> A (in USH1F; dbSNP:rs11003863)" FT /evidence="ECO:0000269|PubMed:22815625" FT /id="VAR_082801" SQ SEQUENCE 1955 AA; 216069 MW; 23BA3A237CB188E7 CRC64; MFRQFYLWTC LASGIILGSL FEICLGQYDD DCKLARGGPP ATIVAIDEES RNGTILVDNM LIKGTAGGPD PTIELSLKDN VDYWVLMDPV KQMLFLNSTG RVLDRDPPMN IHSIVVQVQC INKKVGTIIY HEVRIVVRDR NDNSPTFKHE SYYATVNELT PVGTTIFTGF SGDNGATDID DGPNGQIEYV IQYNPDDPTS NDTFEIPLML TGNIVLRKRL NYEDKTRYFV IIQANDRAQN LNERRTTTTT LTVDVLDGDD LGPMFLPCVL VPNTRDCRPL TYQAAIPELR TPEELNPIIV TPPIQAIDQD RNIQPPSDRP GILYSILVGT PEDYPRFFHM HPRTAELSLL EPVNRDFHQK FDLVIKAEQD NGHPLPAFAG LHIEILDENN QSPYFTMPSY QGYILESAPV GATISDSLNL TSPLRIVALD KDIEDTKDPE LHLFLNDYTS VFTVTQTGIT RYLTLLQPVD REEQQTYTFS ITAFDGVQES EPVIVNIQVM DANDNTPTFP EISYDVYVYT DMRPGDSVIQ LTAVDADEGS NGEITYEILV GAQGDFIINK TTGLITIAPG VEMIVGRTYA LTVQAADNAP PAERRNSICT VYIEVLPPNN QSPPRFPQLM YSLEISEAMR VGAVLLNLQA TDREGDSITY AIENGDPQRV FNLSETTGIL TLGKALDRES TDRYILIITA SDGRPDGTST ATVNIVVTDV NDNAPVFDPY LPRNLSVVEE EANAFVGQVK ATDPDAGING QVHYSLGNFN NLFRITSNGS IYTAVKLNRE VRDYYELVVV ATDGAVHPRH STLTLAIKVL DIDDNSPVFT NSTYTVLVEE NLPAGTTILQ IEAKDVDLGA NVSYRIRSPE VKHFFALHPF TGELSLLRSL DYEAFPDQEA SITFLVEAFD IYGTMPPGIA TVTVIVKDMN DYPPVFSKRI YKGMVAPDAV KGTPITTVYA EDADPPGLPA SRVRYRVDDV QFPYPASIFE VEEDSGRVIT RVNLNEEPTT IFKLVVVAFD DGEPVMSSSA TVKILVLHPG EIPRFTQEEY RPPPVSELAT KGTMVGVISA AAINQSIVYS IVSGNEEDTF GINNITGVIY VNGPLDYETR TSYVLRVQAD SLEVVLANLR VPSKSNTAKV YIEIQDENNH PPVFQKKFYI GGVSEDARMF TSVLRVKATD KDTGNYSVMA YRLIIPPIKE GKEGFVVETY TGLIKTAMLF HNMRRSYFKF QVIATDDYGK GLSGKADVLV SVVNQLDMQV IVSNVPPTLV EKKIEDLTEI LDRYVQEQIP GAKVVVESIG ARRHGDAFSL EDYTKCDLTV YAIDPQTNRA IDRNELFKFL DGKLLDINKD FQPYYGEGGR ILEIRTPEAV TSIKKRGESL GYTEGALLAL AFIIILCCIP AILVVLVSYR QFKVRQAECT KTARIQAALP AAKPAVPAPA PVAAPPPPPP PPPGAHLYEE LGDSSILFLL YHFQQSRGNN SVSEDRKHQQ VVMPFSSNTI EAHKSAHVDG SLKSNKLKSA RKFTFLSDED DLSAHNPLYK ENISQVSTNS DISQRTDFVD PFSPKIQAKS KSLRGPREKI QRLWSQSVSL PRRLMRKVPN RPEIIDLQQW QGTRQKAENE NTGICTNKRG SSNPLLTTEE ANLTEKEEIR QGETLMIEGT EQLKSLSSDS SFCFPRPHFS FSTLPTVSRT VELKSEPNVI SSPAECSLEL SPSRPCVLHS SLSRRETPIC MLPIETERNI FENFAHPPNI SPSACPLPPP PPISPPSPPP APAPLAPPPD ISPFSLFCPP PSPPSIPLPL PPPTFFPLSV STSGPPTPPL LPPFPTPLPP PPPSIPCPPP PSASFLSTEC VCITGVKCTT NLMPAEKIKS SMTQLSTTTV CKTDPQREPK GILRHVKNLA ELEKSVANMY SQIEKNYLRT NVSELQTMCP SEVTNMEITS EQNKGSLNNI VEGTEKQSHS QSTSL //