WHRN_MOUSE
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 03-AUG-2022, entry version 145.
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}.
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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; Q80VW5; -.
DR PRIDE; Q80VW5; -.
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; 155 antibodies from 23 providers.
DR DNASU; 73750; -.
DR Ensembl; ENSMUST00000063650; ENSMUSP00000069664; ENSMUSG00000039137. [Q80VW5-3]
DR Ensembl; ENSMUST00000063672; ENSMUSP00000065838; ENSMUSG00000039137. [Q80VW5-10]
DR Ensembl; ENSMUST00000084510; ENSMUSP00000081557; ENSMUSG00000039137. [Q80VW5-1]
DR Ensembl; ENSMUST00000095037; ENSMUSP00000092647; ENSMUSG00000039137. [Q80VW5-8]
DR Ensembl; ENSMUST00000095038; ENSMUSP00000092648; ENSMUSG00000039137. [Q80VW5-6]
DR Ensembl; ENSMUST00000102867; ENSMUSP00000099931; ENSMUSG00000039137. [Q80VW5-4]
DR Ensembl; ENSMUST00000107393; ENSMUSP00000103016; ENSMUSG00000039137. [Q80VW5-2]
DR Ensembl; ENSMUST00000119294; ENSMUSP00000114030; ENSMUSG00000039137. [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 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; VANQHFI; -.
DR OrthoDB; 168224at2759; -.
DR PhylomeDB; Q80VW5; -.
DR TreeFam; TF325033; -.
DR BioGRID-ORCS; 73750; 4 hits in 71 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 124 other tissues.
DR ExpressionAtlas; Q80VW5; baseline and differential.
DR Genevisible; Q80VW5; MM.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0016020; C:membrane; ISO:MGI.
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; IC: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 DisProt; DP02426; -.
DR Gene3D; 2.30.42.10; -; 3.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR033028; Whirlin.
DR PANTHER; PTHR23116:SF37; PTHR23116:SF37; 1.
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; 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
