ID WHRN_MOUSE Reviewed; 918 AA. AC Q80VW5; A2AGD2; I6MML6; I6MML7; Q3TZC8; Q5MLF1; Q5MLF2; Q5MLF3; Q5MLF4; AC Q5MLF5; Q5MLF6; Q5MLF7; Q5MLF8; Q5MLF9; Q80TC2; Q80VW4; DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot. DT 04-DEC-2007, sequence version 3. DT 24-JAN-2024, entry version 153. DE RecName: Full=Whirlin; GN Name=Whrn {ECO:0000312|MGI:MGI:2682003}; Synonyms=Dfnb31, Kiaa1526; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 9), RP INTERACTION WITH MYO15A, AND SUBCELLULAR LOCATION. RC STRAIN=C57BL/6J; TISSUE=Inner ear; RX PubMed=15654330; DOI=10.1038/ncb1219; RA Belyantseva I.A., Boger E.T., Naz S., Frolenkov G.I., Sellers J.R., RA Ahmed Z.M., Griffith A.J., Friedman T.B.; RT "Myosin-XVa is required for tip localization of whirlin and differential RT elongation of hair-cell stereocilia."; RL Nat. Cell Biol. 7:148-156(2005). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11 AND 12), INTERACTION WITH RPGR, AND RP TISSUE SPECIFICITY. RC STRAIN=C57BL/6J; TISSUE=Retina; RX PubMed=22323458; DOI=10.1167/iovs.11-8845; RA Wright R.N., Hong D.H., Perkins B.; RT "RpgrORF15 connects to the usher protein network through direct RT interactions with multiple whirlin isoforms."; RL Invest. Ophthalmol. Vis. Sci. 53:1519-1529(2012). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10). RC STRAIN=C57BL/6J; TISSUE=Inner ear; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-918 (ISOFORM 4). RC TISSUE=Brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). RN [6] RP DISEASE. RX PubMed=12124769; DOI=10.1002/cne.10301; RA Holme R.H., Kiernan B.W., Brown S.D.M., Steel K.P.; RT "Elongation of hair cell stereocilia is defective in the mouse mutant RT whirler."; RL J. Comp. Neurol. 450:94-102(2002). RN [7] RP DISEASE, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=12833159; DOI=10.1038/ng1208; RA Mburu P., Mustapha M., Varela A., Weil D., El-Amraoui A., Holme R.H., RA Rump A., Hardisty R.E., Blanchard S., Coimbra R.S., Perfettini I., RA Parkinson N., Mallon A.-M., Glenister P., Rogers M.J., Paige A.J., Moir L., RA Clay J., Rosenthal A., Liu X.Z., Blanco G., Steel K.P., Petit C., RA Brown S.D.; RT "Defects in whirlin, a PDZ domain molecule involved in stereocilia RT elongation, cause deafness in the whirler mouse and families with DFNB31."; RL Nat. Genet. 34:421-428(2003). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL RP STAGE. RX PubMed=15590699; DOI=10.1093/hmg/ddi035; RA Kikkawa Y., Mburu P., Morse S., Kominami R., Townsend S., Brown S.D.M.; RT "Mutant analysis reveals whirlin as a dynamic organizer in the growing hair RT cell stereocilium."; RL Hum. Mol. Genet. 14:391-400(2005). RN [9] RP SUBUNIT, INTERACTION WITH LRRC4C; MYO7A AND MYO15A, AND SUBCELLULAR RP LOCATION. RX PubMed=15590698; DOI=10.1093/hmg/ddi036; RA Delprat B., Michel V., Goodyear R., Yamasaki Y., Michalski N., RA El-Amraoui A., Perfettini I., Legrain P., Richardson G., Hardelin J.-P., RA Petit C.; RT "Myosin XVa and whirlin, two deafness gene products required for hair RT bundle growth, are located at the stereocilia tips and interact directly."; RL Hum. Mol. Genet. 14:401-410(2005). RN [10] RP INTERACTION WITH USH2A. RX PubMed=16301217; DOI=10.1093/hmg/ddi416; RA Adato A., Lefevre G., Delprat B., Michel V., Michalski N., Chardenoux S., RA Weil D., El-Amraoui A., Petit C.; RT "Usherin, the defective protein in Usher syndrome type IIA, is likely to be RT a component of interstereocilia ankle links in the inner ear sensory RT cells."; RL Hum. Mol. Genet. 14:3921-3932(2005). RN [11] RP DEVELOPMENTAL STAGE. RX PubMed=16434480; DOI=10.1093/hmg/ddi490; RA van Wijk E., van der Zwaag B., Peters T., Zimmermann U., Te Brinke H., RA Kersten F.F.J., Maerker T., Aller E., Hoefsloot L.H., Cremers C.W.R.J., RA Cremers F.P.M., Wolfrum U., Knipper M., Roepman R., Kremer H.; RT "The DFNB31 gene product whirlin connects to the Usher protein network in RT the cochlea and retina by direct association with USH2A and VLGR1."; RL Hum. Mol. Genet. 15:751-765(2006). RN [12] RP INTERACTION WITH MPP1. RX PubMed=16829577; DOI=10.1073/pnas.0600923103; RA Mburu P., Kikkawa Y., Townsend S., Romero R., Yonekawa H., Brown S.D.; RT "Whirlin complexes with p55 at the stereocilia tip during hair cell RT development."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10973-10978(2006). RN [13] RP DISEASE. RX PubMed=17326148; DOI=10.1002/cm.20199; RA Mogensen M.M., Rzadzinska A., Steel K.P.; RT "The deaf mouse mutant whirler suggests a role for whirlin in actin RT filament dynamics and stereocilia development."; RL Cell Motil. Cytoskeleton 64:496-508(2007). RN [14] RP INTERACTION WITH MPP1, AND SUBCELLULAR LOCATION. RX PubMed=17584769; DOI=10.1093/hmg/ddm147; RA Gosens I., van Wijk E., Kersten F.F., Krieger E., van der Zwaag B., RA Maerker T., Letteboer S.J., Dusseljee S., Peters T., Spierenburg H.A., RA Punte I.M., Wolfrum U., Cremers F.P.M., Kremer H., Roepman R.; RT "MPP1 links the Usher protein network and the Crumbs protein complex in the RT retina."; RL Hum. Mol. Genet. 16:1993-2003(2007). RN [15] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION. RX PubMed=17567809; DOI=10.1523/jneurosci.0342-07.2007; RA Michalski N., Michel V., Bahloul A., Lefevre G., Barral J., Yagi H., RA Chardenoux S., Weil D., Martin P., Hardelin J.P., Sato M., Petit C.; RT "Molecular characterization of the ankle-link complex in cochlear hair RT cells and its role in the hair bundle functioning."; RL J. Neurosci. 27:6478-6488(2007). RN [16] RP FUNCTION, DISRUPTION PHENOTYPE (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND IDENTIFICATION IN THE USH2 COMPLEX. RX PubMed=20502675; DOI=10.1371/journal.pgen.1000955; RA Yang J., Liu X., Zhao Y., Adamian M., Pawlyk B., Sun X., McMillan D.R., RA Liberman M.C., Li T.; RT "Ablation of whirlin long isoform disrupts the USH2 protein complex and RT causes vision and hearing loss."; RL PLoS Genet. 6:E1000955-E1000955(2010). RN [17] RP INTERACTION WITH EPS8. RX PubMed=21236676; DOI=10.1016/j.cub.2010.12.046; RA Manor U., Disanza A., Grati M., Andrade L., Lin H., Di Fiore P.P., RA Scita G., Kachar B.; RT "Regulation of stereocilia length by myosin XVa and whirlin depends on the RT actin-regulatory protein Eps8."; RL Curr. Biol. 21:167-172(2011). RN [18] RP INTERACTION WITH USH2 AND ADGRV1. RX PubMed=23055499; DOI=10.1523/jneurosci.3071-12.2012; RA Grati M., Shin J.B., Weston M.D., Green J., Bhat M.A., Gillespie P.G., RA Kachar B.; RT "Localization of PDZD7 to the stereocilia ankle-link associates this RT scaffolding protein with the Usher syndrome protein network."; RL J. Neurosci. 32:14288-14293(2012). RN [19] RP SUBCELLULAR LOCATION. RC STRAIN=C57BL/6J; TISSUE=Retina; RX PubMed=24334608; DOI=10.1093/hmg/ddt629; RA Zou J., Zheng T., Ren C., Askew C., Liu X.P., Pan B., Holt J.R., Wang Y., RA Yang J.; RT "Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in RT cochlear hair cells and causes hearing loss in mice."; RL Hum. Mol. Genet. 23:2374-2390(2014). RN [20] RP IDENTIFICATION IN THE USH2 COMPLEX, AND SUBUNIT. RX PubMed=25406310; DOI=10.1074/jbc.m114.610535; RA Chen Q., Zou J., Shen Z., Zhang W., Yang J.; RT "Whirlin and PDZ domain-containing 7 (PDZD7) proteins are both required to RT form the quaternary protein complex associated with Usher syndrome type RT 2."; RL J. Biol. Chem. 289:36070-36088(2014). RN [21] {ECO:0007744|PDB:6FDD, ECO:0007744|PDB:6FDE} RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 420-499. RX PubMed=30053338; DOI=10.1111/febs.14614; RA Delhommel F., Cordier F., Saul F., Chataigner L., Haouz A., Wolff N.; RT "Structural plasticity of the HHD2 domain of whirlin."; RL FEBS J. 285:3738-3752(2018). CC -!- FUNCTION: Involved in hearing and vision as member of the USH2 complex CC (PubMed:20502675). Necessary for elongation and maintenance of inner CC and outer hair cell stereocilia in the organ of Corti in the inner ear CC (PubMed:15590699). Involved in the maintenance of the hair bundle ankle CC region, which connects stereocilia in cochlear hair cells of the inner CC ear (PubMed:20502675, PubMed:24334608). In retina photoreceptors, CC required for the maintenance of periciliary membrane complex that seems CC to play a role in regulating intracellular protein transport CC (PubMed:20502675). {ECO:0000269|PubMed:15590699, CC ECO:0000269|PubMed:20502675, ECO:0000269|PubMed:24334608}. CC -!- SUBUNIT: Forms homooligomers (PubMed:15590698, PubMed:25406310). CC Interacts (via C-terminal PDZ domain) with MYO15A; this interaction is CC necessary for localization of WHRN to stereocilia tips CC (PubMed:15654330, PubMed:15590698). Interacts (via C-terminal PDZ CC domain) with MPP1/p55 (PubMed:16829577, PubMed:17584769). Interacts CC with LRRC4C/NGL1 (PubMed:15590698). Interacts with MYO7A CC (PubMed:15590698). Interacts with RPGR (PubMed:22323458). Interacts CC with EPS8 (PubMed:21236676). Interacts with CASK. Interacts with CIB2 CC (By similarity). Component of USH2 complex, composed of ADGRV1, PDZD7, CC USH2A and WHRN (PubMed:20502675, PubMed:25406310). Interacts (via PDZ CC domains) with PDZD7; the interaction is direct (PubMed:25406310). CC Interacts (via N-terminal PDZ domain) with USH2A (via cytoplasmic CC region) (PubMed:16301217, PubMed:20502675, PubMed:23055499). Interacts CC with ADGRV1/MASS1 (via cytoplasmic region) (PubMed:20502675, CC PubMed:23055499). {ECO:0000250|UniProtKB:Q810W9, CC ECO:0000250|UniProtKB:Q9P202, ECO:0000269|PubMed:15590698, CC ECO:0000269|PubMed:15654330, ECO:0000269|PubMed:16301217, CC ECO:0000269|PubMed:16829577, ECO:0000269|PubMed:17584769, CC ECO:0000269|PubMed:20502675, ECO:0000269|PubMed:21236676, CC ECO:0000269|PubMed:22323458, ECO:0000269|PubMed:23055499, CC ECO:0000269|PubMed:25406310}. CC -!- INTERACTION: CC Q80VW5; Q8C031: Lrrc4c; NbExp=4; IntAct=EBI-7417603, EBI-7417983; CC Q80VW5; P70290: Mpp1; NbExp=4; IntAct=EBI-7417603, EBI-8315951; CC Q80VW5; Q9QZZ4: Myo15a; NbExp=5; IntAct=EBI-7417603, EBI-4281382; CC Q80VW5-12; Q9R0X5-5: Rpgr; NbExp=2; IntAct=EBI-6915655, EBI-6915646; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection, stereocilium CC {ECO:0000269|PubMed:15590698, ECO:0000269|PubMed:15590699, CC ECO:0000269|PubMed:15654330, ECO:0000269|PubMed:17567809, CC ECO:0000269|PubMed:20502675, ECO:0000269|PubMed:24334608}. Cell CC projection, growth cone {ECO:0000269|PubMed:17584769}. Photoreceptor CC inner segment {ECO:0000269|PubMed:20502675, CC ECO:0000269|PubMed:24334608}. Synapse {ECO:0000250|UniProtKB:Q810W9}. CC Note=Detected at the level of stereocilia in inner and outer hair cells CC of the cochlea and vestibule. Localizes to both tip and ankle-link CC stereocilia regions. Colocalizes with the growing ends of actin CC filaments (PubMed:15590699, PubMed:15590698, PubMed:15654330, CC PubMed:24334608). Colocalizes with MPP1 in the retina, at the outer CC limiting membrane (OLM), outer plexifirm layer (OPL), basal bodies and CC at the connecting cilium (CC) (PubMed:17584769). In photoreceptors, CC localizes at a plasma membrane microdomain in the apical inner segment CC that surrounds the connecting cilia called periciliary membrane complex CC (PubMed:20502675, PubMed:24334608). {ECO:0000269|PubMed:15590698, CC ECO:0000269|PubMed:15590699, ECO:0000269|PubMed:15654330, CC ECO:0000269|PubMed:17584769, ECO:0000269|PubMed:20502675, CC ECO:0000269|PubMed:24334608}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=12; CC Name=1; CC IsoId=Q80VW5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q80VW5-2; Sequence=VSP_029939, VSP_029941; CC Name=3; CC IsoId=Q80VW5-3; Sequence=VSP_029941; CC Name=4; CC IsoId=Q80VW5-4; Sequence=VSP_029941, VSP_029943; CC Name=5; CC IsoId=Q80VW5-5; Sequence=VSP_029937, VSP_029938, VSP_029941; CC Name=6; CC IsoId=Q80VW5-6; Sequence=VSP_029936; CC Name=7; CC IsoId=Q80VW5-7; Sequence=VSP_029936, VSP_029941; CC Name=8; CC IsoId=Q80VW5-8; Sequence=VSP_029935, VSP_029941; CC Name=9; CC IsoId=Q80VW5-9; Sequence=VSP_029934; CC Name=10; CC IsoId=Q80VW5-10; Sequence=VSP_029940, VSP_029942; CC Name=11; Synonyms=WhirlinNT2; CC IsoId=Q80VW5-11; Sequence=VSP_045294, VSP_045295; CC Name=12; Synonyms=WhirlinNT1; CC IsoId=Q80VW5-12; Sequence=VSP_045293; CC -!- TISSUE SPECIFICITY: Expressed in the retina. Colocalizes with RPGR in CC the photoreceptor connecting cilium, a thin bridge linking the cell CC body and the light-sensing outer segment (at protein level). Detected CC in the inner ear throughout development from embryonic day 12 to 20 CC days after birth. Displays a dynamic pattern of expression after birth, CC demonstrating an ordered appearance and fade-out across stereocilia CC rows. Isoforms 5, 6, 7 and 8 are not detected in the retina CC (PubMed:20502675). {ECO:0000269|PubMed:12833159, CC ECO:0000269|PubMed:15590699, ECO:0000269|PubMed:17567809, CC ECO:0000269|PubMed:20502675, ECO:0000269|PubMed:22323458}. CC -!- DEVELOPMENTAL STAGE: At 10.5 dpc, expressed in the basal plate of the CC spinal cord, in the ventralneural epithelium of the developing brain CC and in the region of the lung bud. At 12.5 dpc, expressed in the CC complete neuroepithelium except for the neocortex. In the developing CC eye, expressed in the inner neuroblastic layer. At 14.5 dpc, detected CC in the intervertebral cartilage, the cortex of the developing kidney, CC the tongue, the region of the urethra and strongly in specific regions CC of the brain, e.g. striatum, optic recess, ventral tegmental area, roof CC of the midbrain, choroid plexus of the lateral ventricles and the CC fourth ventricle. The developing neocortex is devoid of expression. At CC this timepoint, expression is first notable in the inner ear in the CC developing maculae of the saccule and the utricle, in the cristae of CC the semicircular canals and in the vestibulocochlear ganglion. In the CC developing neural retina, a strong signal is present in the inner CC neuroblastic layer. At 16.5 dpc, expression is very similar to that at CC 14.5 dpc. At 18.5 dpc, expression is mainly as in 16.5 dpc. Expression CC in the ganglion layers of the retina decreases and is no longer CC detected in the innermost region of these layers. From postnatal day 7 CC (P7) onwards, also the developing photoreceptor cells express whirlin CC (PubMed:16434480). Expression decreases by 11 days after birth in inner CC ear hair cells and by 14 days after birth in outer ear hair cells. CC Expressed in vestibular hair cells at high levels through to adulthood. CC {ECO:0000269|PubMed:15590699, ECO:0000269|PubMed:16434480}. CC -!- DISEASE: Note=Defects in Whrn are the cause of the phenotype whirler CC (wi). Mutants are characterized by deafness due to malformation of the CC cochlear inner and outer hair cells and by circling behavior. CC Stereocilia are shorter and wider than in wild-type animals and there CC is a decrease in the number of actin filaments in inner and outer hair CC cells. The number of outer hair cell stereocilia is reduced with CC increased spacing between them. {ECO:0000269|PubMed:12124769, CC ECO:0000269|PubMed:12833159, ECO:0000269|PubMed:17326148}. CC -!- DISRUPTION PHENOTYPE: Mutant mice for isoform 1 appear viable and CC comparable to their wild-type littermates in growth characteristics, CC reproductive performance and general health (PubMed:20502675). At 2 and CC 9 months of age, knockouts show a profound hearing loss across all CC cochlear frequencies (PubMed:20502675). At 28 to 33 months, they show CC signs for retinal degeneration such as a thinner photoreceptor nuclear CC layer and outer segments shortened (PubMed:20502675). CC {ECO:0000269|PubMed:20502675}. CC -!- MISCELLANEOUS: [Isoform 3]: Major isoform. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 11]: May be due to intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 12]: May be due to intron retention. CC {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; AY739114; AAV87519.1; -; mRNA. DR EMBL; AY739115; AAV87520.1; -; mRNA. DR EMBL; AY739116; AAV87521.1; -; mRNA. DR EMBL; AY739117; AAV87522.1; -; mRNA. DR EMBL; AY739118; AAV87523.1; -; mRNA. DR EMBL; AY739119; AAV87524.1; -; mRNA. DR EMBL; AY739120; AAV87525.1; -; mRNA. DR EMBL; AY739121; AAV87526.1; -; mRNA. DR EMBL; AY739122; AAV87527.1; -; mRNA. DR EMBL; HQ148552; AEL23234.1; -; mRNA. DR EMBL; HQ148553; AEL23235.1; -; mRNA. DR EMBL; AK157955; BAE34281.1; -; mRNA. DR EMBL; AL683828; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK122523; BAC65805.1; -; mRNA. DR CCDS; CCDS18255.1; -. [Q80VW5-1] DR CCDS; CCDS18256.1; -. [Q80VW5-4] DR CCDS; CCDS18257.1; -. [Q80VW5-3] DR CCDS; CCDS38778.1; -. [Q80VW5-2] DR RefSeq; NP_001008791.1; NM_001008791.2. [Q80VW5-1] DR RefSeq; NP_001008792.1; NM_001008792.2. [Q80VW5-2] DR RefSeq; NP_001008793.1; NM_001008793.2. [Q80VW5-4] DR RefSeq; NP_001263300.1; NM_001276371.1. [Q80VW5-12] DR RefSeq; NP_082916.1; NM_028640.2. [Q80VW5-3] DR RefSeq; XP_017175899.1; XM_017320410.1. DR PDB; 6FDD; X-ray; 1.75 A; A/B/C/D/E/F=420-499. DR PDB; 6FDE; X-ray; 1.85 A; A=420-499. DR PDB; 6Y38; X-ray; 1.70 A; A/B=821-915. DR PDB; 6Y9N; X-ray; 1.93 A; A=821-918. DR PDB; 6Y9O; X-ray; 1.63 A; A=821-918. DR PDB; 6Y9P; X-ray; 3.17 A; A/B/E/G/I/K=821-918. DR PDB; 6Y9Q; X-ray; 1.31 A; B=821-918. DR PDBsum; 6FDD; -. DR PDBsum; 6FDE; -. DR PDBsum; 6Y38; -. DR PDBsum; 6Y9N; -. DR PDBsum; 6Y9O; -. DR PDBsum; 6Y9P; -. DR PDBsum; 6Y9Q; -. DR AlphaFoldDB; Q80VW5; -. DR SMR; Q80VW5; -. DR ComplexPortal; CPX-2501; USH2 complex. DR CORUM; Q80VW5; -. DR DIP; DIP-42047N; -. DR IntAct; Q80VW5; 5. DR MINT; Q80VW5; -. DR STRING; 10090.ENSMUSP00000081557; -. DR iPTMnet; Q80VW5; -. DR PhosphoSitePlus; Q80VW5; -. DR PaxDb; 10090-ENSMUSP00000081557; -. DR ProteomicsDB; 299675; -. [Q80VW5-1] DR ProteomicsDB; 299676; -. [Q80VW5-2] DR ProteomicsDB; 299677; -. [Q80VW5-3] DR ProteomicsDB; 299678; -. [Q80VW5-4] DR ProteomicsDB; 299679; -. [Q80VW5-5] DR ProteomicsDB; 299680; -. [Q80VW5-6] DR ProteomicsDB; 299681; -. [Q80VW5-7] DR ProteomicsDB; 299682; -. [Q80VW5-8] DR ProteomicsDB; 299683; -. [Q80VW5-9] DR ProteomicsDB; 299684; -. [Q80VW5-10] DR ProteomicsDB; 299685; -. [Q80VW5-11] DR ProteomicsDB; 299686; -. [Q80VW5-12] DR ABCD; Q80VW5; 13 sequenced antibodies. DR Antibodypedia; 29951; 163 antibodies from 23 providers. DR DNASU; 73750; -. DR Ensembl; ENSMUST00000063650.10; ENSMUSP00000069664.4; ENSMUSG00000039137.19. [Q80VW5-3] DR Ensembl; ENSMUST00000063672.10; ENSMUSP00000065838.4; ENSMUSG00000039137.19. [Q80VW5-10] DR Ensembl; ENSMUST00000084510.8; ENSMUSP00000081557.2; ENSMUSG00000039137.19. [Q80VW5-1] DR Ensembl; ENSMUST00000095037.2; ENSMUSP00000092647.2; ENSMUSG00000039137.19. [Q80VW5-8] DR Ensembl; ENSMUST00000095038.8; ENSMUSP00000092648.2; ENSMUSG00000039137.19. [Q80VW5-6] DR Ensembl; ENSMUST00000102867.8; ENSMUSP00000099931.2; ENSMUSG00000039137.19. [Q80VW5-4] DR Ensembl; ENSMUST00000107393.8; ENSMUSP00000103016.2; ENSMUSG00000039137.19. [Q80VW5-2] DR Ensembl; ENSMUST00000119294.8; ENSMUSP00000114030.2; ENSMUSG00000039137.19. [Q80VW5-7] DR GeneID; 73750; -. DR KEGG; mmu:73750; -. DR UCSC; uc008tgf.1; mouse. [Q80VW5-9] DR UCSC; uc008tgg.1; mouse. [Q80VW5-5] DR UCSC; uc008tgh.2; mouse. [Q80VW5-1] DR UCSC; uc008tgi.2; mouse. [Q80VW5-4] DR UCSC; uc008tgj.2; mouse. [Q80VW5-2] DR UCSC; uc008tgk.2; mouse. [Q80VW5-3] DR UCSC; uc008tgm.1; mouse. [Q80VW5-8] DR UCSC; uc008tgn.1; mouse. [Q80VW5-7] DR UCSC; uc008tgp.2; mouse. [Q80VW5-10] DR UCSC; uc033icr.1; mouse. [Q80VW5-12] DR AGR; MGI:2682003; -. DR CTD; 25861; -. DR MGI; MGI:2682003; Whrn. DR VEuPathDB; HostDB:ENSMUSG00000039137; -. DR eggNOG; KOG3528; Eukaryota. DR GeneTree; ENSGT00950000183002; -. DR HOGENOM; CLU_014984_0_0_1; -. DR InParanoid; Q80VW5; -. DR OMA; TMVNQTR; -. DR OrthoDB; 2962072at2759; -. DR PhylomeDB; Q80VW5; -. DR TreeFam; TF325033; -. DR BioGRID-ORCS; 73750; 4 hits in 76 CRISPR screens. DR ChiTaRS; Whrn; mouse. DR PRO; PR:Q80VW5; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q80VW5; Protein. DR Bgee; ENSMUSG00000039137; Expressed in retinal neural layer and 126 other cell types or tissues. DR ExpressionAtlas; Q80VW5; baseline and differential. DR GO; GO:0005884; C:actin filament; IDA:MGI. DR GO; GO:0097440; C:apical dendrite; ISO:MGI. DR GO; GO:0044303; C:axon collateral; ISO:MGI. DR GO; GO:0036064; C:ciliary basal body; IDA:MGI. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043198; C:dendritic shaft; ISO:MGI. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:1990075; C:periciliary membrane compartment; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:MGI. DR GO; GO:0001917; C:photoreceptor inner segment; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0098793; C:presynapse; ISO:MGI. DR GO; GO:0002141; C:stereocilia ankle link; IDA:UniProtKB. DR GO; GO:0002142; C:stereocilia ankle link complex; IDA:MGI. DR GO; GO:0032420; C:stereocilium; IDA:UniProtKB. DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI. DR GO; GO:0032426; C:stereocilium tip; IDA:MGI. DR GO; GO:1990696; C:USH2 complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:MGI. DR GO; GO:0021694; P:cerebellar Purkinje cell layer formation; IMP:CACAO. DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IDA:UniProtKB. DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI. DR GO; GO:0045184; P:establishment of protein localization; IMP:MGI. DR GO; GO:0060113; P:inner ear receptor cell differentiation; NAS:ComplexPortal. DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IMP:UniProtKB. DR GO; GO:1990227; P:paranodal junction maintenance; IMP:CACAO. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI. DR GO; GO:0001895; P:retina homeostasis; IDA:UniProtKB. DR GO; GO:0050953; P:sensory perception of light stimulus; ISO:MGI. DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI. DR CDD; cd07356; HN_L-whirlin_R1_like; 1. DR CDD; cd07357; HN_L-whirlin_R2_like; 1. DR CDD; cd00992; PDZ_signaling; 3. DR DisProt; DP02426; -. DR Gene3D; 1.20.1160.20; -; 2. DR Gene3D; 2.30.42.10; -; 3. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR047056; Whirlin_HN-like_dom1. DR InterPro; IPR033028; Whirlin_HN-like_dom2. DR PANTHER; PTHR23116; PDZ DOMAIN CONTAINING WHIRLIN AND HARMONIN-RELATED; 1. DR PANTHER; PTHR23116:SF37; WHIRLIN; 1. DR Pfam; PF00595; PDZ; 3. DR SMART; SM00228; PDZ; 3. DR SUPFAM; SSF50156; PDZ domain-like; 3. DR PROSITE; PS50106; PDZ; 3. DR Genevisible; Q80VW5; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell projection; Cytoplasm; Deafness; KW Hearing; Phosphoprotein; Reference proteome; Repeat; Synapse. FT CHAIN 1..918 FT /note="Whirlin" FT /id="PRO_0000065969" FT DOMAIN 141..224 FT /note="PDZ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 280..362 FT /note="PDZ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 827..910 FT /note="PDZ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 240..266 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 387..407 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 503..538 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 560..824 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 240..257 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 519..538 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 560..576 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 588..602 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 649..673 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 691..722 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 752..800 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 696 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9P202" FT VAR_SEQ 1..552 FT /note="Missing (in isoform 9)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029934" FT VAR_SEQ 1..503 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029935" FT VAR_SEQ 1..442 FT /note="Missing (in isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029936" FT VAR_SEQ 1..357 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029937" FT VAR_SEQ 323..918 FT /note="Missing (in isoform 12)" FT /evidence="ECO:0000303|PubMed:22323458" FT /id="VSP_045293" FT VAR_SEQ 358..402 FT /note="KDVGRLPHARTTVDQTKWIASSRIGESVANSAGFPGDHTEEGTSK -> MTT FT WCHRPRVRWSGSCVCGDHQHNARSHSLPRSLDSSGLCPSVFQ (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029938" FT VAR_SEQ 390 FT /note="G -> GSGLR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15654330" FT /id="VSP_029939" FT VAR_SEQ 544..571 FT /note="ERLLWLIDLMENTLDLEGTGETTQGSTN -> VSHPCPILGEKVRARIRCFP FT PKPRVPHL (in isoform 10)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_029940" FT VAR_SEQ 544..554 FT /note="Missing (in isoform 2, isoform 3, isoform 4, isoform FT 5, isoform 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:12693553, FT ECO:0000303|PubMed:15654330" FT /id="VSP_029941" FT VAR_SEQ 555..566 FT /note="NTLDLEGTGETT -> VPSFCRGRLGVP (in isoform 11)" FT /evidence="ECO:0000303|PubMed:22323458" FT /id="VSP_045294" FT VAR_SEQ 567..918 FT /note="Missing (in isoform 11)" FT /evidence="ECO:0000303|PubMed:22323458" FT /id="VSP_045295" FT VAR_SEQ 572..918 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_029942" FT VAR_SEQ 758 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12693553, FT ECO:0000303|PubMed:15654330" FT /id="VSP_029943" FT CONFLICT 504 FT /note="M -> V (in Ref. 3; BAE34281)" FT /evidence="ECO:0000305" FT HELIX 425..434 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 437..451 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 457..467 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 471..474 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 476..481 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 486..488 FT /evidence="ECO:0007829|PDB:6FDD" FT HELIX 489..495 FT /evidence="ECO:0007829|PDB:6FDD" FT STRAND 826..831 FT /evidence="ECO:0007829|PDB:6Y9Q" FT STRAND 834..836 FT /evidence="ECO:0007829|PDB:6Y38" FT STRAND 839..842 FT /evidence="ECO:0007829|PDB:6Y9Q" FT STRAND 847..849 FT /evidence="ECO:0007829|PDB:6Y9Q" FT STRAND 853..857 FT /evidence="ECO:0007829|PDB:6Y9Q" FT HELIX 862..865 FT /evidence="ECO:0007829|PDB:6Y9Q" FT STRAND 874..878 FT /evidence="ECO:0007829|PDB:6Y9Q" FT HELIX 888..900 FT /evidence="ECO:0007829|PDB:6Y9Q" FT STRAND 905..914 FT /evidence="ECO:0007829|PDB:6Y9Q" SQ SEQUENCE 918 AA; 98012 MW; 7D5EA44DE0645AA4 CRC64; MNAQLDGLSV SSSSTGSLGS AAAAAGGGGG AGLRLLSANV RQLHQALTAL LSEPEREQFT HCLNAYHARR NVFDLVRTLR VLLDSPVKRR LLPMLRLVIP RSDQLLFDQY TAEGLYLPAT TPYRQPAWAA PDGAGPGEVR LVSLRRAKAH EGLGFSIRGG SEHGVGIYVS LVEPGSLAEK EGLRVGDQIL RVNDKSLARV THAEAVKALK GSKKLVLSVY SAGRIPGGYV TNHIYTWVDP QGRSTSPPSS LPQPHGSTLR QREDDRRSTL HLLQSGDEKK VNLVLGDGRS LGLTIRGGAE YGLGIYITGV DPGSEAESSG LKVGDQILEV NGRSFLNILH DEAVKLLKSS RHLILTVKDV GRLPHARTTV DQTKWIASSR IGESVANSAG FPGDHTEEGT SKPGFYKGPA GSQVTLSSLG NQTRALLDDQ ARHLLTEQER ATMMYYLAQY RGGTISVEAM VMALFELLNT HAKFSLLSEV RSIISPQDLD RFDHLVLRRE IESMKARQPP GPGVGDTYSM VSYSDTGSST GSHGTSTTVS SARERLLWLI DLMENTLDLE GTGETTQGST NALPDVSVDD VKSPSEDLPG IKPPPPPPPL AQGHDRLLGQ PRKPGREDPA PLSSAAHSGI VFSAPRNRSP PPGTAPTPGP SSAQDSPSSP IYASISHANP SSRKPLDTHL ALVNQHPIGP FPRVQSPPHL KSPPAETPGA GACLPPPSPS EHPDAVGANQ HFVLVEVHRP DSEPDVNEVR ALPQTRTAST LSQLSDSGQT LSEDSGVDAG ETEASTSGRG RQTASAKNKN GKEQPRTERT AEGANKPPGL LEPTSTLVRV RKSAATLGIA IEGGANTRQP LPRIVTIQRG GSAHNCGQLK VGHVILEVNG QTLRGKEHKE AARIIAEAFK TKERDYIDFL VTEFNVML //