USH1C_HUMAN
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 03-AUG-2022, entry version 195.
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 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 [19]
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 [20]
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 [21]
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 (Probable). Part of a complex composed of USH1C,
CC USH1G and MYO7A (PubMed:21709241). Interacts with F-actin (By
CC similarity). Interacts with USH2A (PubMed:16301216). Interacts with
CC SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C-
CC terminus of USHBP1 (PubMed:11311560). Interacts (via N-terminus and PDZ
CC 2 domain) with CDH23 (PubMed:19297620). Interacts with USH1G
CC (PubMed:12588794, PubMed:20142502). Interacts with MYO7B
CC (PubMed:24725409, PubMed:26812017). Interacts with CDHR2 and CDHR5; may
CC mediate their interaction with MYO7B at the microvilli tip
CC (PubMed:24725409, PubMed:26812017). Interacts (via PDZ 1 domain) with
CC ANKS4B (PubMed:26812018, PubMed:26812017). Interacts (via PDZ 1 domain)
CC with 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:0000305|PubMed:24725409, 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}. Note=Colocalizes with F-actin (By
CC similarity). Detected at the tip of cochlear hair cell stereocilia (By
CC similarity). Enriched in microvilli of the intestinal brush border
CC (PubMed:24725409). {ECO:0000250|UniProtKB:Q9ES64,
CC ECO:0000269|PubMed:24725409}.
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";
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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 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 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 PaxDb; Q9Y6N9; -.
DR PeptideAtlas; Q9Y6N9; -.
DR PRIDE; 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; 272 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 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; 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; HQTMDVV; -.
DR OrthoDB; 1252899at2759; -.
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; 3 hits in 1072 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 147 other tissues.
DR ExpressionAtlas; Q9Y6N9; baseline and differential.
DR Genevisible; Q9Y6N9; HS.
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:0051015; F:actin filament binding; IEA:InterPro.
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; IMP: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 Gene3D; 2.30.42.10; -; 3.
DR InterPro; IPR030237; Harmonin.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR23116:SF36; PTHR23116:SF36; 2.
DR Pfam; PF00595; PDZ; 3.
DR SMART; SM00228; PDZ; 3.
DR SUPFAM; SSF50156; SSF50156; 3.
DR PROSITE; PS50106; PDZ; 3.
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 208..214
FT /evidence="ECO:0007829|PDB:1X5N"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:2KBS"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:1X5N"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:1X5N"
FT STRAND 235..241
FT /evidence="ECO:0007829|PDB:1X5N"
FT TURN 246..251
FT /evidence="ECO:0007829|PDB:1X5N"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:1X5N"
FT HELIX 273..280
FT /evidence="ECO:0007829|PDB:1X5N"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:1X5N"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:1X5N"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:1X5N"
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
