ID USH1C_HUMAN Reviewed; 552 AA. AC Q9Y6N9; A8K423; Q7RTU8; Q96B29; Q9UM04; Q9UM17; Q9UPC3; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 3. DT 27-MAR-2024, entry version 204. DE RecName: Full=Harmonin; DE AltName: Full=Antigen NY-CO-38/NY-CO-37; DE AltName: Full=Autoimmune enteropathy-related antigen AIE-75; DE AltName: Full=Protein PDZ-73; DE AltName: Full=Renal carcinoma antigen NY-REN-3; DE AltName: Full=Usher syndrome type-1C protein; GN Name=USH1C; Synonyms=AIE75; 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] (ISOFORMS 1 AND 3), AND VARIANT ASP-519. RC TISSUE=Colon cancer; RX PubMed=9610721; RX DOI=10.1002/(sici)1097-0215(19980529)76:5<652::aid-ijc7>3.0.co;2-p; RA Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., RA Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.; RT "Characterization of human colon cancer antigens recognized by autologous RT antibodies."; RL Int. J. Cancer 76:652-658(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Duodenum; RX PubMed=10500064; DOI=10.1016/s0016-5085(99)70340-9; RA Kobayashi I., Imamura K., Kubota M., Ishikawa S., Yamada M., Tonoki H., RA Okano M., Storch W.B., Moriuchi T., Sakiyama Y., Kobayashi K.; RT "Identification of an autoimmune enteropathy-related 75-kilodalton RT antigen."; RL Gastroenterology 117:823-830(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-519. RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT ASP-519. RC TISSUE=Colon; 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 [7] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [8] RP INVOLVEMENT IN USH1C, AND ALTERNATIVE SPLICING (ISOFORM 5). RX PubMed=10973247; DOI=10.1038/79171; RA Verpy E., Leibovici M., Zwaenepoel I., Liu X.-Z., Gal A., Salem N., RA Mansour A., Blanchard S., Kobayashi I., Keats B.J.B., Slim R., Petit C.; RT "A defect in harmonin, a PDZ domain-containing protein expressed in the RT inner ear sensory hair cells, underlies Usher syndrome type 1C."; RL Nat. Genet. 26:51-55(2000). RN [9] RP INTERACTION WITH USHBP1, AND DOMAIN. RX PubMed=11311560; DOI=10.1016/s0378-1119(01)00378-x; RA Ishikawa S., Kobayashi I., Hamada J., Tada M., Hirai A., Furuuchi K., RA Takahashi Y., Ba Y., Moriuchi T.; RT "Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ- RT domain protein AIE-75."; RL Gene 267:101-110(2001). RN [10] RP INVOLVEMENT IN DFNB18A. RX PubMed=12107438; DOI=10.1007/s00439-002-0732-4; RA Ahmed Z.M., Smith T.N., Riazuddin S., Makishima T., Ghosh M., Bokhari S., RA Menon P.S., Deshmukh D., Griffith A.J., Riazuddin S., Friedman T.B., RA Wilcox E.R.; RT "Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are RT allelic mutations of USHIC."; RL Hum. Genet. 110:527-531(2002). RN [11] RP INTERACTION WITH USH1G, AND TISSUE SPECIFICITY. RX PubMed=12588794; DOI=10.1093/hmg/ddg051; RA Weil D., El-Amraoui A., Masmoudi S., Mustapha M., Kikkawa Y., Laine S., RA Delmaghani S., Adato A., Nadifi S., Zina Z.B., Hamel C., Gal A., Ayadi H., RA Yonekawa H., Petit C.; RT "Usher syndrome type I G (USH1G) is caused by mutations in the gene RT encoding SANS, a protein that associates with the USH1C protein, RT harmonin."; RL Hum. Mol. Genet. 12:463-471(2003). RN [12] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [13] RP INTERACTION WITH SLC4A7 AND USH2A, AND DOMAIN. RX PubMed=16301216; DOI=10.1093/hmg/ddi417; RA Reiners J., van Wijk E., Maerker T., Zimmermann U., Juergens K., RA te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., Wolfrum U.; RT "Scaffold protein harmonin (USH1C) provides molecular links between Usher RT syndrome type 1 and type 2."; RL Hum. Mol. Genet. 14:3933-3943(2005). RN [14] RP INTERACTION WITH DOCK4, AND DOMAIN. RX PubMed=16464467; DOI=10.1016/j.jmb.2006.01.017; RA Yan D., Li F., Hall M.L., Sage C., Hu W.H., Giallourakis C., Upadhyay G., RA Ouyang X.M., Du L.L., Bethea J.R., Chen Z.Y., Yajnik V., Liu X.Z.; RT "An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the RT inner ear and binds to harmonin (USH1C)."; RL J. Mol. Biol. 357:755-764(2006). RN [15] RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH MYO7A AND USH1G. RX PubMed=21709241; DOI=10.1073/pnas.1104161108; RA Grati M., Kachar B.; RT "Myosin VIIa and sans localization at stereocilia upper tip-link density RT implicates these Usher syndrome proteins in mechanotransduction."; RL Proc. Natl. Acad. Sci. U.S.A. 108:11476-11481(2011). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION OF THE IMAC COMPLEX, RP INTERACTION WITH CDHR2; CDHR5 AND MYO7B, AND DOMAIN. RX PubMed=24725409; DOI=10.1016/j.cell.2014.01.067; RA Crawley S.W., Shifrin D.A. Jr., Grega-Larson N.E., McConnell R.E., RA Benesh A.E., Mao S., Zheng Y., Zheng Q.Y., Nam K.T., Millis B.A., RA Kachar B., Tyska M.J.; RT "Intestinal brush border assembly driven by protocadherin-based RT intermicrovillar adhesion."; RL Cell 157:433-446(2014). RN [17] RP FUNCTION, IDENTIFICATION OF THE IMAC COMPLEX, INTERACTION WITH ANKS4B AND RP MYO7B, DOMAIN, AND REGION. RX PubMed=26812018; DOI=10.1016/j.devcel.2015.12.022; RA Crawley S.W., Weck M.L., Grega-Larson N.E., Shifrin D.A. Jr., Tyska M.J.; RT "ANKS4B is essential for intermicrovillar adhesion complex formation."; RL Dev. Cell 36:190-200(2016). RN [18] RP IDENTIFICATION OF THE IMAC COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=32209652; DOI=10.1074/jbc.ra120.012820; RA Choi M.S., Graves M.J., Matoo S., Storad Z.A., El Sheikh Idris R.A., RA Weck M.L., Smith Z.B., Tyska M.J., Crawley S.W.; RT "The small EF-hand protein CALML4 functions as a critical myosin light RT chain within the intermicrovillar adhesion complex."; RL J. Biol. Chem. 295:9281-9296(2020). RN [19] RP STRUCTURE BY NMR OF 197-301. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the second PDZ domain of harmonin protein."; RL Submitted (NOV-2005) to the PDB data bank. RN [20] RP STRUCTURE BY NMR OF 1-80 AND 208-299 IN COMPLEX WITH CDH23, SUBCELLULAR RP LOCATION, AND INTERACTION WITH CDH23. RX PubMed=19297620; DOI=10.1073/pnas.0901819106; RA Pan L., Yan J., Wu L., Zhang M.; RT "Assembling stable hair cell tip link complex via multidentate interactions RT between harmonin and cadherin 23."; RL Proc. Natl. Acad. Sci. U.S.A. 106:5575-5580(2009). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-192 IN COMPLEX WITH USH1G, RP INTERACTION WITH USH1G, MUTAGENESIS OF ARG-103, DOMAIN, AND SUBCELLULAR RP LOCATION. RX PubMed=20142502; DOI=10.1073/pnas.0911385107; RA Yan J., Pan L., Chen X., Wu L., Zhang M.; RT "The structure of the harmonin/sans complex reveals an unexpected RT interaction mode of the two Usher syndrome proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 107:4040-4045(2010). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-194 IN COMPLEX WITH ANKS4B, RP INTERACTION WITH CDHR2 AND MYO7B, REGION, AND DOMAIN. RX PubMed=26812017; DOI=10.1016/j.devcel.2015.12.020; RA Li J., He Y., Lu Q., Zhang M.; RT "Mechanistic basis of organization of the Harmonin/USH1C-mediated brush RT border microvilli tip-link complex."; RL Dev. Cell 36:179-189(2016). CC -!- FUNCTION: Anchoring/scaffolding protein that is a part of the CC functional network formed by USH1C, USH1G, CDH23 and MYO7A that CC mediates mechanotransduction in cochlear hair cells. Required for CC normal development and maintenance of cochlear hair cell bundles (By CC similarity). As part of the intermicrovillar adhesion complex/IMAC CC plays a role in brush border differentiation, controlling microvilli CC organization and length. Probably plays a central regulatory role in CC the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the CC microvilli tips (PubMed:24725409, PubMed:26812018). CC {ECO:0000250|UniProtKB:Q9ES64, ECO:0000269|PubMed:24725409, CC ECO:0000269|PubMed:26812018}. CC -!- SUBUNIT: Part of the IMAC/intermicrovillar adhesion CC complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, CC USH1C, CDHR2 and CDHR5 (PubMed:26812018, PubMed:32209652, CC PubMed:24725409). Part of a complex composed of USH1C, USH1G and MYO7A CC (PubMed:21709241). Interacts with F-actin (By similarity). Interacts CC with USH2A (PubMed:16301216). Interacts with SLC4A7 (PubMed:16301216). CC Interacts (via PDZ1 domain) with the C-terminus of USHBP1 CC (PubMed:11311560). Interacts (via N-terminus and PDZ 2 domain) with CC CDH23 (PubMed:19297620). Interacts with USH1G (PubMed:12588794, CC PubMed:20142502). Interacts with MYO7B (PubMed:24725409, CC PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their CC interaction with MYO7B at the microvilli tip (PubMed:24725409, CC PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B CC (PubMed:26812018, PubMed:26812017). Interacts (via PDZ 1 domain) with CC DOCK4 (PubMed:16464467). {ECO:0000250|UniProtKB:Q9ES64, CC ECO:0000269|PubMed:11311560, ECO:0000269|PubMed:12588794, CC ECO:0000269|PubMed:16301216, ECO:0000269|PubMed:16464467, CC ECO:0000269|PubMed:19297620, ECO:0000269|PubMed:20142502, CC ECO:0000269|PubMed:21709241, ECO:0000269|PubMed:24725409, CC ECO:0000269|PubMed:26812017, ECO:0000269|PubMed:26812018, CC ECO:0000269|PubMed:32209652, ECO:0000305|PubMed:24725409, CC ECO:0000305|PubMed:26812018}. CC -!- INTERACTION: CC Q9Y6N9; Q9UBT7: CTNNAL1; NbExp=3; IntAct=EBI-954308, EBI-514206; CC Q9Y6N9; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-954308, EBI-2548751; CC Q9Y6N9; P63000: RAC1; NbExp=3; IntAct=EBI-954308, EBI-413628; CC Q9Y6N9; Q495M9: USH1G; NbExp=13; IntAct=EBI-954308, EBI-8601749; CC Q9Y6N9-1; Q9BYE9: CDHR2; NbExp=2; IntAct=EBI-9541226, EBI-493793; CC Q9Y6N9-1; Q9HBB8: CDHR5; NbExp=2; IntAct=EBI-9541226, EBI-9540696; CC Q9Y6N9-4; Q8WXG9-1: ADGRV1; NbExp=3; IntAct=EBI-11523636, EBI-11621707; CC Q9Y6N9-4; Q8N8V4: ANKS4B; NbExp=5; IntAct=EBI-11523636, EBI-9658517; CC Q9Y6N9-4; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-11523636, EBI-744099; CC Q9Y6N9-4; Q9Y5F1: PCDHB12; NbExp=3; IntAct=EBI-11523636, EBI-12012016; CC Q9Y6N9-4; P54646: PRKAA2; NbExp=3; IntAct=EBI-11523636, EBI-1383852; CC Q9Y6N9-4; O75445-1: USH2A; NbExp=3; IntAct=EBI-11523636, EBI-11621644; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20142502}. CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:19297620, CC ECO:0000269|PubMed:21709241}. Cell projection, microvillus CC {ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:32209652}. CC Note=Colocalizes with F-actin (By similarity). Detected at the tip of CC cochlear hair cell stereocilia (By similarity). Enriched in microvilli CC of the intestinal brush border (PubMed:24725409, PubMed:32209652). CC {ECO:0000250|UniProtKB:Q9ES64, ECO:0000269|PubMed:24725409, CC ECO:0000269|PubMed:32209652}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q9Y6N9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y6N9-2; Sequence=VSP_003789; CC Name=3; CC IsoId=Q9Y6N9-3; Sequence=VSP_003790; CC Name=4; CC IsoId=Q9Y6N9-4; Sequence=VSP_007422; CC Name=5; CC IsoId=Q9Y6N9-5; Sequence=VSP_043520, VSP_043521; CC -!- TISSUE SPECIFICITY: Expressed in small intestine, colon, kidney, eye CC and weakly in pancreas. Expressed also in vestibule of the inner ear. CC {ECO:0000269|PubMed:12588794}. CC -!- DOMAIN: The PDZ 1 domain mediates interaction with ANKS4B, DOCK4, CC USHBP1, USH1G, SLC4A7. {ECO:0000269|PubMed:16301216, CC ECO:0000269|PubMed:16464467, ECO:0000269|PubMed:20142502, CC ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812017, CC ECO:0000269|PubMed:26812018}. CC -!- DOMAIN: The N-terminal region constitutes an independently folded CC domain that has structural similarity with the CCM2 C-terminus, despite CC very low sequence similarity. {ECO:0000269|PubMed:20142502}. CC -!- DISEASE: Usher syndrome 1C (USH1C) [MIM:276904]: 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:10973247}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Deafness, autosomal recessive, 18A (DFNB18A) [MIM:602092]: 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:12107438}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC18049.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mutations of the USH1C gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/ush1cmut.htm"; 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; AF039700; AAC18049.1; ALT_FRAME; mRNA. DR EMBL; AF039699; AAC18048.1; -; mRNA. DR EMBL; AB006955; BAA81739.1; -; mRNA. DR EMBL; AB018687; BAA81740.1; -; mRNA. DR EMBL; AK290788; BAF83477.1; -; mRNA. DR EMBL; AC124799; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016057; AAH16057.1; -; mRNA. DR EMBL; CH471064; EAW68432.1; -; Genomic_DNA. DR EMBL; BK000147; DAA00086.1; -; mRNA. DR CCDS; CCDS31438.1; -. [Q9Y6N9-1] DR CCDS; CCDS73265.1; -. [Q9Y6N9-4] DR CCDS; CCDS7825.1; -. [Q9Y6N9-5] DR RefSeq; NP_001284693.1; NM_001297764.1. [Q9Y6N9-4] DR RefSeq; NP_005700.2; NM_005709.3. [Q9Y6N9-1] DR RefSeq; NP_710142.1; NM_153676.3. [Q9Y6N9-5] DR PDB; 1X5N; NMR; -; A=201-301. DR PDB; 2KBQ; NMR; -; A=1-80. DR PDB; 2KBR; NMR; -; A=1-80. DR PDB; 2KBS; NMR; -; A=208-299. DR PDB; 2LSR; NMR; -; A=1-80. DR PDB; 3K1R; X-ray; 2.30 A; A=1-192. DR PDB; 5F3X; X-ray; 2.65 A; A/C=1-194. DR PDB; 5MV8; X-ray; 1.88 A; B=428-552. DR PDB; 5MV9; X-ray; 2.60 A; B=428-552. DR PDB; 5XBF; X-ray; 1.80 A; B=428-552. DR PDB; 7X2E; X-ray; 1.85 A; A=193-370. DR PDBsum; 1X5N; -. DR PDBsum; 2KBQ; -. DR PDBsum; 2KBR; -. DR PDBsum; 2KBS; -. DR PDBsum; 2LSR; -. DR PDBsum; 3K1R; -. DR PDBsum; 5F3X; -. DR PDBsum; 5MV8; -. DR PDBsum; 5MV9; -. DR PDBsum; 5XBF; -. DR PDBsum; 7X2E; -. DR AlphaFoldDB; Q9Y6N9; -. DR BMRB; Q9Y6N9; -. DR SMR; Q9Y6N9; -. DR BioGRID; 115392; 32. DR CORUM; Q9Y6N9; -. DR DIP; DIP-41473N; -. DR ELM; Q9Y6N9; -. DR IntAct; Q9Y6N9; 31. DR MINT; Q9Y6N9; -. DR iPTMnet; Q9Y6N9; -. DR PhosphoSitePlus; Q9Y6N9; -. DR BioMuta; USH1C; -. DR DMDM; 160113087; -. DR EPD; Q9Y6N9; -. DR jPOST; Q9Y6N9; -. DR MassIVE; Q9Y6N9; -. DR MaxQB; Q9Y6N9; -. DR PeptideAtlas; Q9Y6N9; -. DR ProteomicsDB; 86750; -. [Q9Y6N9-1] DR ProteomicsDB; 86751; -. [Q9Y6N9-2] DR ProteomicsDB; 86752; -. [Q9Y6N9-3] DR ProteomicsDB; 86753; -. [Q9Y6N9-4] DR ProteomicsDB; 86754; -. [Q9Y6N9-5] DR Antibodypedia; 24888; 296 antibodies from 33 providers. DR DNASU; 10083; -. DR Ensembl; ENST00000005226.12; ENSP00000005226.7; ENSG00000006611.17. [Q9Y6N9-5] DR Ensembl; ENST00000318024.9; ENSP00000317018.4; ENSG00000006611.17. [Q9Y6N9-1] DR Ensembl; ENST00000526313.5; ENSP00000432236.1; ENSG00000006611.17. [Q9Y6N9-3] DR Ensembl; ENST00000527020.5; ENSP00000436934.1; ENSG00000006611.17. [Q9Y6N9-4] DR Ensembl; ENST00000527720.5; ENSP00000432944.1; ENSG00000006611.17. [Q9Y6N9-2] DR GeneID; 10083; -. DR KEGG; hsa:10083; -. DR MANE-Select; ENST00000005226.12; ENSP00000005226.7; NM_153676.4; NP_710142.1. [Q9Y6N9-5] DR UCSC; uc001mne.4; human. [Q9Y6N9-1] DR AGR; HGNC:12597; -. DR CTD; 10083; -. DR DisGeNET; 10083; -. DR GeneCards; USH1C; -. DR GeneReviews; USH1C; -. DR HGNC; HGNC:12597; USH1C. DR HPA; ENSG00000006611; Tissue enhanced (intestine, kidney). DR MalaCards; USH1C; -. DR MIM; 276900; phenotype. DR MIM; 276904; phenotype. DR MIM; 602092; phenotype. DR MIM; 605242; gene. DR neXtProt; NX_Q9Y6N9; -. DR OpenTargets; ENSG00000006611; -. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR Orphanet; 231169; Usher syndrome type 1. DR PharmGKB; PA37226; -. DR VEuPathDB; HostDB:ENSG00000006611; -. DR eggNOG; KOG3528; Eukaryota. DR GeneTree; ENSGT00950000183002; -. DR HOGENOM; CLU_019813_0_0_1; -. DR InParanoid; Q9Y6N9; -. DR OMA; LQLEPMD; -. DR OrthoDB; 2913575at2759; -. DR PhylomeDB; Q9Y6N9; -. DR TreeFam; TF325033; -. DR PathwayCommons; Q9Y6N9; -. 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; Q9Y6N9; -. DR SIGNOR; Q9Y6N9; -. DR BioGRID-ORCS; 10083; 4 hits in 1150 CRISPR screens. DR ChiTaRS; USH1C; human. DR EvolutionaryTrace; Q9Y6N9; -. DR GeneWiki; USH1C; -. DR GenomeRNAi; 10083; -. DR Pharos; Q9Y6N9; Tbio. DR PRO; PR:Q9Y6N9; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9Y6N9; Protein. DR Bgee; ENSG00000006611; Expressed in mucosa of transverse colon and 149 other cell types or tissues. DR ExpressionAtlas; Q9Y6N9; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IDA:HGNC-UCL. DR GO; GO:0005903; C:brush border; IDA:UniProtKB. DR GO; GO:0005929; C:cilium; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005902; C:microvillus; IDA:UniProtKB. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:BHF-UCL. DR GO; GO:0001750; C:photoreceptor outer segment; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL. DR GO; GO:0002142; C:stereocilia ankle link complex; IBA:GO_Central. DR GO; GO:0032420; C:stereocilium; ISS:BHF-UCL. DR GO; GO:0032426; C:stereocilium tip; IBA:GO_Central. DR GO; GO:0045202; C:synapse; ISS:BHF-UCL. DR GO; GO:0030507; F:spectrin binding; IDA:MGI. DR GO; GO:0051017; P:actin filament bundle assembly; ISS:BHF-UCL. DR GO; GO:1904970; P:brush border assembly; IDA:UniProtKB. DR GO; GO:0050957; P:equilibrioception; IMP:HGNC-UCL. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:HGNC-UCL. DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; ISS:BHF-UCL. DR GO; GO:0042472; P:inner ear morphogenesis; ISS:BHF-UCL. DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; ISS:BHF-UCL. DR GO; GO:0030046; P:parallel actin filament bundle assembly; ISS:BHF-UCL. DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:HGNC-UCL. DR GO; GO:1904106; P:protein localization to microvillus; IMP:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0032532; P:regulation of microvillus length; ISS:UniProtKB. DR GO; GO:0046549; P:retinal cone cell development; IBA:GO_Central. 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; cd07353; harmonin_N; 1. DR CDD; cd00992; PDZ_signaling; 3. DR Gene3D; 1.20.1160.20; -; 1. DR Gene3D; 2.30.42.10; -; 3. DR InterPro; IPR030237; Harmonin_N. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR PANTHER; PTHR23116:SF36; HARMONIN; 1. DR PANTHER; PTHR23116; PDZ DOMAIN CONTAINING WHIRLIN AND HARMONIN-RELATED; 1. DR Pfam; PF00595; PDZ; 3. DR Pfam; PF21219; USH1C_N; 1. DR SMART; SM00228; PDZ; 3. DR SUPFAM; SSF50156; PDZ domain-like; 3. DR PROSITE; PS50106; PDZ; 3. DR Genevisible; Q9Y6N9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell projection; Coiled coil; KW Cytoplasm; Cytoskeleton; Deafness; Differentiation; Hearing; KW Non-syndromic deafness; Phosphoprotein; Reference proteome; Repeat; KW Retinitis pigmentosa; Usher syndrome. FT CHAIN 1..552 FT /note="Harmonin" FT /id="PRO_0000065727" FT DOMAIN 87..169 FT /note="PDZ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 211..293 FT /note="PDZ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 452..537 FT /note="PDZ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 1..86 FT /note="N-terminal domain" FT /evidence="ECO:0000269|PubMed:20142502" FT REGION 194..552 FT /note="Mediates interaction with MYO7B" FT /evidence="ECO:0000269|PubMed:26812017, FT ECO:0000269|PubMed:26812018" FT REGION 401..427 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 310..377 FT /evidence="ECO:0000255" FT MOD_RES 219 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9ES64" FT VAR_SEQ 1..31 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10500064" FT /id="VSP_003789" FT VAR_SEQ 274..292 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_007422" FT VAR_SEQ 404..552 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9610721" FT /id="VSP_003790" FT VAR_SEQ 404..427 FT /note="YDQGVEPELEPADDLDGGTEEQGE -> SFGWFYRYDGKFPTIRKKGKDKKK FT AKYGSLQDLRKNKKELEFEQKLYKEKEEMLEKEKQLKINRLAQEVSETEREDLEESEKI FT QYWVERLCQTRLEQISSADNEISEMTTGPPPPPPSVSPLAPPLRRFAGGLHLHTTDLDD FT IPLDMFYYPPKTPSALPVMPHPPPSNPPHKVPAPPVLPLSGHVSASSSPWVQRTPPPIP FT IPPPPSVPTQDLTPTRPLPSALEEALSNHPFRTGDTGNPVEDWEAKNHSGKPTNSPVPE FT QSFPPTPKTFCPSPQPPRGPGVSTISKPVMVHQEPNFIYRPAVKSEVLPQEMLKRMVVY FT QTAFR (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_043520" FT VAR_SEQ 550..552 FT /note="TFF -> ASLPSSVAESPQPVRKLLEDRAAVHRHGFLLQLEPTDLLLKSKRG FT NQIHR (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_043521" FT VARIANT 519 FT /note="E -> D (in dbSNP:rs1064074)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9610721" FT /id="VAR_012320" FT MUTAGEN 103 FT /note="R->H: Strongly reduced affinity for USH1G." FT /evidence="ECO:0000269|PubMed:20142502" FT CONFLICT 103 FT /note="R -> S (in Ref. 2; BAA81739)" FT /evidence="ECO:0000305" FT CONFLICT 280 FT /note="S -> N (in Ref. 1; AAC18049/AAC18048)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="A -> T (in Ref. 2; BAA81739)" FT /evidence="ECO:0000305" FT HELIX 2..16 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 20..36 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 39..46 FT /evidence="ECO:0007829|PDB:3K1R" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 53..56 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 57..62 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 71..77 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 86..91 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 106..108 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 110..117 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 122..125 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 147..154 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 156..166 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 169..172 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 181..184 FT /evidence="ECO:0007829|PDB:3K1R" FT HELIX 185..191 FT /evidence="ECO:0007829|PDB:3K1R" FT STRAND 210..214 FT /evidence="ECO:0007829|PDB:7X2E" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:2KBS" FT STRAND 223..228 FT /evidence="ECO:0007829|PDB:7X2E" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:1X5N" FT STRAND 235..241 FT /evidence="ECO:0007829|PDB:7X2E" FT HELIX 246..249 FT /evidence="ECO:0007829|PDB:7X2E" FT STRAND 257..261 FT /evidence="ECO:0007829|PDB:7X2E" FT HELIX 271..278 FT /evidence="ECO:0007829|PDB:7X2E" FT STRAND 282..289 FT /evidence="ECO:0007829|PDB:7X2E" FT TURN 290..293 FT /evidence="ECO:0007829|PDB:7X2E" FT HELIX 294..297 FT /evidence="ECO:0007829|PDB:7X2E" FT HELIX 300..367 FT /evidence="ECO:0007829|PDB:7X2E" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:5XBF" FT HELIX 445..448 FT /evidence="ECO:0007829|PDB:5XBF" FT STRAND 453..459 FT /evidence="ECO:0007829|PDB:5XBF" FT STRAND 466..471 FT /evidence="ECO:0007829|PDB:5XBF" FT STRAND 478..484 FT /evidence="ECO:0007829|PDB:5XBF" FT HELIX 489..493 FT /evidence="ECO:0007829|PDB:5XBF" FT STRAND 501..505 FT /evidence="ECO:0007829|PDB:5XBF" FT HELIX 515..527 FT /evidence="ECO:0007829|PDB:5XBF" FT STRAND 528..538 FT /evidence="ECO:0007829|PDB:5XBF" SQ SEQUENCE 552 AA; 62211 MW; 7E75CEE873C57F41 CRC64; MDRKVAREFR HKVDFLIEND AEKDYLYDVL RMYHQTMDVA VLVGDLKLVI NEPSRLPLFD AIRPLIPLKH QVEYDQLTPR RSRKLKEVRL DRLHPEGLGL SVRGGLEFGC GLFISHLIKG GQADSVGLQV GDEIVRINGY SISSCTHEEV INLIRTKKTV SIKVRHIGLI PVKSSPDEPL TWQYVDQFVS ESGGVRGSLG SPGNRENKEK KVFISLVGSR GLGCSISSGP IQKPGIFISH VKPGSLSAEV GLEIGDQIVE VNGVDFSNLD HKEAVNVLKS SRSLTISIVA AAGRELFMTD RERLAEARQR ELQRQELLMQ KRLAMESNKI LQEQQEMERQ RRKEIAQKAA EENERYRKEM EQIVEEEEKF KKQWEEDWGS KEQLLLPKTI TAEVHPVPLR KPKYDQGVEP ELEPADDLDG GTEEQGEQDF RKYEEGFDPY SMFTPEQIMG KDVRLLRIKK EGSLDLALEG GVDSPIGKVV VSAVYERGAA ERHGGIVKGD EIMAINGKIV TDYTLAEAEA ALQKAWNQGG DWIDLVVAVC PPKEYDDELT FF //