MYO6_HUMAN
ID MYO6_HUMAN Reviewed; 1294 AA.
AC Q9UM54; A6H8V4; E1P540; Q5TEM5; Q5TEM6; Q5TEM7; Q9BZZ7; Q9UEG2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Unconventional myosin-VI;
DE AltName: Full=Unconventional myosin-6;
GN Name=MYO6 {ECO:0000312|HGNC:HGNC:7605}; Synonyms=KIAA0389;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9259267; DOI=10.1093/hmg/6.8.1225;
RA Avraham K.B., Hasson T., Sobe T., Balsara B., Testa J.R., Skvorak A.B.,
RA Morton C.C., Copeland N.G., Jenkins N.A.;
RT "Characterization of unconventional MYO6, the human homologue of the gene
RT responsible for deafness in Snell's waltzer mice.";
RL Hum. Mol. Genet. 6:1225-1231(1997).
RN [2]
RP SEQUENCE REVISION.
RA Avraham K.B.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kuehn M.H., Hageman G.S.;
RT "Genomic organization of the human myosin VI gene (MYO6), a candidate gene
RT for neurosensory and storage disorders.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 5).
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1102-1294 (ISOFORM 6).
RC TISSUE=Salivary gland;
RX PubMed=16344560; DOI=10.1101/gr.4039406;
RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA Sugano S.;
RT "Diversification of transcriptional modulation: large-scale identification
RT and characterization of putative alternative promoters of human genes.";
RL Genome Res. 16:55-65(2006).
RN [9]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION BY PAK.
RC TISSUE=Intestine;
RX PubMed=9852149; DOI=10.1083/jcb.143.6.1535;
RA Buss F., Kendrick-Jones J., Lionne C., Knight A.E., Cote G.P.,
RA Paul Luzio J.;
RT "The localization of myosin VI at the Golgi complex and leading edge of
RT fibroblasts and its phosphorylation and recruitment into membrane ruffles
RT of A431 cells after growth factor stimulation.";
RL J. Cell Biol. 143:1535-1545(1998).
RN [10]
RP FUNCTION.
RX PubMed=10519557; DOI=10.1038/46835;
RA Wells A.L., Lin A.W., Chen L.-Q., Safer D., Cain S.M., Hasson T.,
RA Carragher B.O., Milligan R.A., Sweeney H.L.;
RT "Myosin VI is an actin-based motor that moves backwards.";
RL Nature 401:505-508(1999).
RN [11]
RP FUNCTION IN ENDOCYTOSIS, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING.
RX PubMed=11447109; DOI=10.1093/emboj/20.14.3676;
RA Buss F., Arden S.D., Lindsay M., Luzio J.P., Kendrick-Jones J.;
RT "Myosin VI isoform localized to clathrin-coated vesicles with a role in
RT clathrin-mediated endocytosis.";
RL EMBO J. 20:3676-3684(2001).
RN [12]
RP INTERACTION WITH DAB2, AND SUBCELLULAR LOCATION.
RX PubMed=11967127; DOI=10.1034/j.1600-0854.2002.30503.x;
RA Morris S.M., Arden S.D., Roberts R.C., Kendrick-Jones J., Cooper J.A.,
RA Luzio J.P., Buss F.;
RT "Myosin VI binds to and localises with Dab2, potentially linking receptor-
RT mediated endocytosis and the actin cytoskeleton.";
RL Traffic 3:331-341(2002).
RN [13]
RP INTERACTION WITH CFTR.
RX PubMed=15247260; DOI=10.1074/jbc.m403141200;
RA Swiatecka-Urban A., Boyd C., Coutermarsh B., Karlson K.H., Barnaby R.,
RA Aschenbrenner L., Langford G.M., Hasson T., Stanton B.A.;
RT "Myosin VI regulates endocytosis of the cystic fibrosis transmembrane
RT conductance regulator.";
RL J. Biol. Chem. 279:38025-38031(2004).
RN [14]
RP SUBUNIT.
RX PubMed=15044955; DOI=10.1038/sj.emboj.7600180;
RA Lister I., Schmitz S., Walker M., Trinick J., Buss F., Veigel C.,
RA Kendrick-Jones J.;
RT "A monomeric myosin VI with a large working stroke.";
RL EMBO J. 23:1729-1738(2004).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16949370; DOI=10.1016/j.molcel.2006.07.005;
RA Vreugde S., Ferrai C., Miluzio A., Hauben E., Marchisio P.C., Crippa M.P.,
RA Bussi M., Biffo S.;
RT "Nuclear myosin VI enhances RNA polymerase II-dependent transcription.";
RL Mol. Cell 23:749-755(2006).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16507995; DOI=10.1128/mcb.26.6.2175-2186.2006;
RA Jung E.J., Liu G., Zhou W., Chen X.;
RT "Myosin VI is a mediator of the p53-dependent cell survival pathway.";
RL Mol. Cell. Biol. 26:2175-2186(2006).
RN [17]
RP SAH DOMAIN.
RX PubMed=18511944; DOI=10.1038/nsmb.1429;
RA Spink B.J., Sivaramakrishnan S., Lipfert J., Doniach S., Spudich J.A.;
RT "Long single alpha-helical tail domains bridge the gap between structure
RT and function of myosin VI.";
RL Nat. Struct. Mol. Biol. 15:591-597(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-267 AND THR-405, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-405, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP FUNCTION, AND IDENTIFICATION IN DISP COMPLEX.
RX PubMed=29467281; DOI=10.15252/embr.201744884;
RA O'Loughlin T., Masters T.A., Buss F.;
RT "The MYO6 interactome reveals adaptor complexes coordinating early endosome
RT and cytoskeletal dynamics.";
RL EMBO Rep. 19:0-0(2018).
RN [22]
RP VARIANT DFNA22 TYR-442.
RX PubMed=11468689; DOI=10.1086/323156;
RA Melchionda S., Ahituv N., Bisceglia L., Sobe T., Glaser F., Rabionet R.,
RA Arbones M.L., Notarangelo A., Di Iorio E., Carella M., Zelante L.,
RA Estivill X., Avraham K.B., Gasparini P.;
RT "MYO6, the human homologue of the gene responsible for deafness in Snell's
RT waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.";
RL Am. J. Hum. Genet. 69:635-640(2001).
RN [23]
RP VARIANT DFNB37 VAL-216.
RX PubMed=12687499; DOI=10.1086/375122;
RA Ahmed Z.M., Morell R.J., Riazuddin S., Gropman A., Shaukat S., Ahmad M.M.,
RA Mohiddin S.A., Fananapazir L., Caruso R.C., Husnain T., Khan S.N.,
RA Riazuddin S., Griffith A.J., Friedman T.B., Wilcox E.R.;
RT "Mutations of MYO6 are associated with recessive deafness, DFNB37.";
RL Am. J. Hum. Genet. 72:1315-1322(2003).
RN [24]
RP VARIANT DFNHCM ARG-246.
RX PubMed=15060111; DOI=10.1136/jmg.2003.011973;
RA Mohiddin S.A., Ahmed Z.M., Griffith A.J., Tripodi D., Friedman T.B.,
RA Fananapazir L., Morell R.J.;
RT "Novel association of hypertrophic cardiomyopathy, sensorineural deafness,
RT and a mutation in unconventional myosin VI (MYO6).";
RL J. Med. Genet. 41:309-314(2004).
CC -!- FUNCTION: Myosins are actin-based motor molecules with ATPase activity
CC (By similarity). Unconventional myosins serve in intracellular
CC movements (By similarity). Myosin 6 is a reverse-direction motor
CC protein that moves towards the minus-end of actin filaments
CC (PubMed:10519557). Has slow rate of actin-activated ADP release due to
CC weak ATP binding (By similarity). Functions in a variety of
CC intracellular processes such as vesicular membrane trafficking and cell
CC migration (By similarity). Required for the structural integrity of the
CC Golgi apparatus via the p53-dependent pro-survival pathway
CC (PubMed:16507995). Appears to be involved in a very early step of
CC clathrin-mediated endocytosis in polarized epithelial cells
CC (PubMed:11447109). May act as a regulator of F-actin dynamics (By
CC similarity). As part of the DISP complex, may regulate the association
CC of septins with actin and thereby regulate the actin cytoskeleton
CC (PubMed:29467281). May play a role in transporting DAB2 from the plasma
CC membrane to specific cellular targets (By similarity). May play a role
CC in the extension and network organization of neurites (By similarity).
CC Required for structural integrity of inner ear hair cells (By
CC similarity). Modulates RNA polymerase II-dependent transcription
CC (PubMed:16949370). {ECO:0000250|UniProtKB:Q29122,
CC ECO:0000250|UniProtKB:Q64331, ECO:0000269|PubMed:10519557,
CC ECO:0000269|PubMed:11447109, ECO:0000269|PubMed:16507995,
CC ECO:0000269|PubMed:16949370, ECO:0000269|PubMed:29467281}.
CC -!- SUBUNIT: Homodimer; dimerization seems to implicate the unfolding of
CC the three-helix bundle region creating an additional calmodulin binding
CC site, and cargo binding (By similarity). Able to function as a monomer
CC under specific conditions in vitro (PubMed:15044955). Forms a complex
CC with CFTR and DAB2 in the apical membrane of epithelial cells
CC (PubMed:15247260). Component of the DISP/DOCK7-induced septin
CC displacement complex, at least composed of DOCK7, LRCH3 and MYO6
CC (PubMed:29467281). Binding to calmodulin through a unique insert, not
CC found in other myosins, located in the neck region between the motor
CC domain and the IQ domain appears to contribute to the directionality
CC reversal (By similarity). This interaction occurs only if the C-
CC terminal lobe of calmodulin is occupied by calcium (By similarity).
CC Interaction with F-actin/ACTN1 occurs only at the apical brush border
CC domain of the proximal tubule cells (By similarity). Interacts with
CC DAB2 (PubMed:11967127). In vitro, the C-terminal globular tail binds a
CC C-terminal region of DAB2 (By similarity). Interacts with CFTR
CC (PubMed:15247260). Interacts with OPTN (By similarity). Interacts with
CC CABP5 (By similarity). {ECO:0000250|UniProtKB:E1BPK6,
CC ECO:0000250|UniProtKB:Q29122, ECO:0000250|UniProtKB:Q64331,
CC ECO:0000250|UniProtKB:Q9I8D1, ECO:0000269|PubMed:11967127,
CC ECO:0000269|PubMed:15044955, ECO:0000269|PubMed:15247260,
CC ECO:0000269|PubMed:29467281}.
CC -!- INTERACTION:
CC Q9UM54; P98082: DAB2; NbExp=3; IntAct=EBI-350606, EBI-1171238;
CC Q9UM54; P98078: Dab2; Xeno; NbExp=4; IntAct=EBI-350606, EBI-1391846;
CC Q9UM54; Q9Z0G0: Gipc1; Xeno; NbExp=4; IntAct=EBI-350606, EBI-300855;
CC Q9UM54-1; Q9UM54-1: MYO6; NbExp=3; IntAct=EBI-15706115, EBI-15706115;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:16507995}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16507995}. Golgi apparatus
CC {ECO:0000269|PubMed:16507995}. Nucleus {ECO:0000269|PubMed:16507995,
CC ECO:0000269|PubMed:16949370}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:16507995}. Membrane, clathrin-coated pit
CC {ECO:0000269|PubMed:11447109}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000269|PubMed:11447109}. Cell projection, filopodium
CC {ECO:0000269|PubMed:9852149}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:16507995}. Cell projection, microvillus
CC {ECO:0000269|PubMed:9852149}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:16949370}. Note=Also present in endocyctic vesicles
CC (PubMed:16507995). Translocates from membrane ruffles, endocytic
CC vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and
CC nucleus through induction by p53 and p53-induced DNA damage
CC (PubMed:16507995). Recruited into membrane ruffles from cell surface by
CC EGF-stimulation (PubMed:9852149). Colocalizes with DAB2 in clathrin-
CC coated pits/vesicles (PubMed:11967127). Colocalizes with OPTN at the
CC Golgi complex and in vesicular structures close to the plasma membrane
CC (By similarity). {ECO:0000250|UniProtKB:Q9I8D1,
CC ECO:0000269|PubMed:11967127, ECO:0000269|PubMed:16507995,
CC ECO:0000269|PubMed:9852149}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane {ECO:0000269|PubMed:11447109}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:11447109}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=3;
CC IsoId=Q9UM54-3; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9UM54-1; Sequence=VSP_022332;
CC Name=2;
CC IsoId=Q9UM54-2; Sequence=VSP_007985;
CC Name=4;
CC IsoId=Q9UM54-4; Sequence=VSP_022333;
CC Name=5;
CC IsoId=Q9UM54-5; Sequence=VSP_007985, VSP_022333;
CC Name=6;
CC IsoId=Q9UM54-6; Sequence=VSP_042208;
CC -!- TISSUE SPECIFICITY: Expressed in most tissues examined including heart,
CC brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary,
CC small intestine and colon. Highest levels in brain, pancreas, testis
CC and small intestine. Also expressed in fetal brain and cochlea. Isoform
CC 1 and isoform 2, containing the small insert, and isoform 4, containing
CC neither insert, are expressed in unpolarized epithelial cells.
CC {ECO:0000269|PubMed:9259267}.
CC -!- DOMAIN: Divided into three regions: a N-terminal motor (head) domain,
CC followed by a neck domain consisting of a calmodulin-binding linker
CC domain and a single IQ motif, and a C-terminal tail region with a
CC three-helix bundle region, a SAH domain and a unique globular domain
CC required for interaction with other proteins such as cargo-binding.
CC {ECO:0000250|UniProtKB:Q29122}.
CC -!- DOMAIN: The SAH (single alpha-helix) region is characterized by a high
CC content of charged residues which are predicted to stabilize the alpha-
CC helical structure by ionic bonds (PubMed:18511944). Its contribution to
CC the mechanism confering the myosin movement on actin filaments is
CC debated (PubMed:18511944). {ECO:0000269|PubMed:18511944}.
CC -!- PTM: Phosphorylation in the motor domain, induced by EGF, results in
CC translocation of MYO6 from the cell surface to membrane ruffles and
CC affects F-actin dynamics. Phosphorylated in vitro by p21-activated
CC kinase (PAK). {ECO:0000269|PubMed:9852149}.
CC -!- DISEASE: Deafness, autosomal dominant, 22 (DFNA22) [MIM:606346]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. DFNA22 is progressive and postlingual, with onset during
CC childhood. By the age of approximately 50 years, affected individuals
CC invariably have profound sensorineural deafness.
CC {ECO:0000269|PubMed:11468689}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Deafness, autosomal recessive, 37 (DFNB37) [MIM:607821]: 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:12687499}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Deafness, autosomal dominant 22, with hypertrophic
CC cardiomyopathy (DFNHCM) [MIM:606346]: An autosomal dominant
CC sensorineural deafness associated with hypertrophic cardiomyopathy.
CC {ECO:0000269|PubMed:15060111}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Myosin family. {ECO:0000305}.
CC -!- CAUTION: Represents an unconventional myosin. This protein should not
CC be confused with the conventional myosin-6 (MYH6). {ECO:0000305}.
CC -!- CAUTION: Originally predicted to contain a coiled coil domain but
CC generally accepted to contain a stable SAH domain instead.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20843.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U90236; AAC51654.2; -; mRNA.
DR EMBL; AF229111; AAK00229.1; -; Genomic_DNA.
DR EMBL; AF229082; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229083; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229084; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229085; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229086; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229087; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229088; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229089; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229090; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229091; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229092; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229093; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229094; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229095; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229096; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229097; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229098; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229099; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229100; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229101; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229102; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229103; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229104; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229105; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229106; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229107; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229108; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229109; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AF229110; AAK00229.1; JOINED; Genomic_DNA.
DR EMBL; AL109897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136093; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB002387; BAA20843.2; ALT_INIT; mRNA.
DR EMBL; CH471051; EAW48730.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48731.1; -; Genomic_DNA.
DR EMBL; BC146764; AAI46765.1; -; mRNA.
DR EMBL; BP333853; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS34487.1; -. [Q9UM54-1]
DR CCDS; CCDS75481.1; -. [Q9UM54-2]
DR RefSeq; NP_001287828.1; NM_001300899.1. [Q9UM54-2]
DR RefSeq; NP_004990.3; NM_004999.3. [Q9UM54-1]
DR PDB; 2N0Z; NMR; -; A=1080-1122.
DR PDB; 2N10; NMR; -; A=1080-1131.
DR PDB; 2N11; NMR; -; A=998-1071.
DR PDB; 2N12; NMR; -; A=1050-1131.
DR PDB; 2N13; NMR; -; A/D=1080-1122.
DR PDB; 6E5N; NMR; -; B=1050-1131.
DR PDB; 6J56; X-ray; 1.80 A; A/B=1166-1294.
DR PDBsum; 2N0Z; -.
DR PDBsum; 2N10; -.
DR PDBsum; 2N11; -.
DR PDBsum; 2N12; -.
DR PDBsum; 2N13; -.
DR PDBsum; 6E5N; -.
DR PDBsum; 6J56; -.
DR AlphaFoldDB; Q9UM54; -.
DR SMR; Q9UM54; -.
DR BioGRID; 110730; 324.
DR DIP; DIP-33123N; -.
DR IntAct; Q9UM54; 127.
DR MINT; Q9UM54; -.
DR STRING; 9606.ENSP00000358994; -.
DR iPTMnet; Q9UM54; -.
DR MetOSite; Q9UM54; -.
DR PhosphoSitePlus; Q9UM54; -.
DR SwissPalm; Q9UM54; -.
DR BioMuta; MYO6; -.
DR DMDM; 122065628; -.
DR EPD; Q9UM54; -.
DR jPOST; Q9UM54; -.
DR MassIVE; Q9UM54; -.
DR MaxQB; Q9UM54; -.
DR PaxDb; Q9UM54; -.
DR PeptideAtlas; Q9UM54; -.
DR PRIDE; Q9UM54; -.
DR ProteomicsDB; 85177; -. [Q9UM54-3]
DR ProteomicsDB; 85178; -. [Q9UM54-1]
DR ProteomicsDB; 85179; -. [Q9UM54-2]
DR ProteomicsDB; 85180; -. [Q9UM54-4]
DR ProteomicsDB; 85181; -. [Q9UM54-5]
DR ProteomicsDB; 85182; -. [Q9UM54-6]
DR Antibodypedia; 4385; 147 antibodies from 27 providers.
DR DNASU; 4646; -.
DR Ensembl; ENST00000369977.8; ENSP00000358994.3; ENSG00000196586.17. [Q9UM54-1]
DR Ensembl; ENST00000369985.9; ENSP00000359002.3; ENSG00000196586.17. [Q9UM54-2]
DR Ensembl; ENST00000615563.4; ENSP00000478013.1; ENSG00000196586.17. [Q9UM54-2]
DR GeneID; 4646; -.
DR KEGG; hsa:4646; -.
DR MANE-Select; ENST00000369977.8; ENSP00000358994.3; NM_004999.4; NP_004990.3. [Q9UM54-1]
DR UCSC; uc003pih.2; human. [Q9UM54-3]
DR CTD; 4646; -.
DR DisGeNET; 4646; -.
DR GeneCards; MYO6; -.
DR GeneReviews; MYO6; -.
DR HGNC; HGNC:7605; MYO6.
DR HPA; ENSG00000196586; Low tissue specificity.
DR MalaCards; MYO6; -.
DR MIM; 600970; gene.
DR MIM; 606346; phenotype.
DR MIM; 607821; phenotype.
DR neXtProt; NX_Q9UM54; -.
DR OpenTargets; ENSG00000196586; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 228012; Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome.
DR PharmGKB; PA31410; -.
DR VEuPathDB; HostDB:ENSG00000196586; -.
DR eggNOG; KOG0163; Eukaryota.
DR GeneTree; ENSGT00940000156078; -.
DR InParanoid; Q9UM54; -.
DR OMA; TCPLDEV; -.
DR PhylomeDB; Q9UM54; -.
DR TreeFam; TF351449; -.
DR PathwayCommons; Q9UM54; -.
DR Reactome; R-HSA-190873; Gap junction degradation.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013422; RHOBTB1 GTPase cycle.
DR SignaLink; Q9UM54; -.
DR SIGNOR; Q9UM54; -.
DR BioGRID-ORCS; 4646; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; MYO6; human.
DR GeneWiki; MYO6; -.
DR GenomeRNAi; 4646; -.
DR Pharos; Q9UM54; Tbio.
DR PRO; PR:Q9UM54; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UM54; protein.
DR Bgee; ENSG00000196586; Expressed in amniotic fluid and 194 other tissues.
DR ExpressionAtlas; Q9UM54; baseline and differential.
DR Genevisible; Q9UM54; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031941; C:filamentous actin; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016591; C:RNA polymerase II, holoenzyme; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016461; C:unconventional myosin complex; TAS:UniProtKB.
DR GO; GO:0003779; F:actin binding; TAS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0003774; F:cytoskeletal motor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000146; F:microfilament motor activity; IBA:GO_Central.
DR GO; GO:0060001; F:minus-end directed microfilament motor activity; NAS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0030048; P:actin filament-based movement; ISS:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IBA:GO_Central.
DR GO; GO:0042472; P:inner ear morphogenesis; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0051046; P:regulation of secretion; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0030050; P:vesicle transport along actin filament; IBA:GO_Central.
DR CDD; cd01382; MYSc_Myo6; 1.
DR Gene3D; 2.30.30.360; -; 1.
DR Gene3D; 3.40.850.10; -; 2.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR032412; Myosin-VI_CBD.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR004009; Myosin_N.
DR InterPro; IPR008989; Myosin_S1_N.
DR InterPro; IPR036114; MYSc_Myo6.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF16521; Myosin-VI_CBD; 1.
DR Pfam; PF00063; Myosin_head; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00242; MYSc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51456; MYOSIN_MOTOR; 1.
DR PROSITE; PS51844; SH3_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cardiomyopathy; Cell membrane; Cell projection;
KW Coated pit; Cytoplasm; Cytoplasmic vesicle; Deafness; Disease variant;
KW Endocytosis; Golgi apparatus; Hearing; Membrane; Motor protein; Myosin;
KW Non-syndromic deafness; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..1294
FT /note="Unconventional myosin-VI"
FT /id="PRO_0000123464"
FT DOMAIN 2..53
FT /note="Myosin N-terminal SH3-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01190"
FT DOMAIN 57..771
FT /note="Myosin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00782"
FT DOMAIN 814..834
FT /note="IQ"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 273..317
FT /note="Responsible for slow ATPase activity"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 665..672
FT /note="Actin-binding"
FT /evidence="ECO:0000255"
FT REGION 782..810
FT /note="Required for binding calmodulin"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 835..916
FT /note="Three-helix bundle"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 917..984
FT /note="SAH"
FT /evidence="ECO:0000269|PubMed:18511944"
FT REGION 934..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1118
FT /note="Interaction with OPTN"
FT /evidence="ECO:0000250|UniProtKB:Q9I8D1"
FT BINDING 151..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 405
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64331"
FT MOD_RES 1025
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64331"
FT MOD_RES 1155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64331"
FT VAR_SEQ 1037..1068
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:9259267"
FT /id="VSP_007985"
FT VAR_SEQ 1037..1045
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9205841"
FT /id="VSP_022332"
FT VAR_SEQ 1147..1156
FT /note="DFAPFLNNSP -> A (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:16344560"
FT /id="VSP_042208"
FT VAR_SEQ 1147..1155
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_022333"
FT VARIANT 216
FT /note="E -> V (in DFNB37; dbSNP:rs121912559)"
FT /evidence="ECO:0000269|PubMed:12687499"
FT /id="VAR_016209"
FT VARIANT 246
FT /note="H -> R (in DFNHCM; dbSNP:rs121912560)"
FT /evidence="ECO:0000269|PubMed:15060111"
FT /id="VAR_029988"
FT VARIANT 442
FT /note="C -> Y (in DFNA22)"
FT /evidence="ECO:0000269|PubMed:11468689"
FT /id="VAR_012110"
FT HELIX 999..1022
FT /evidence="ECO:0007829|PDB:2N11"
FT HELIX 1026..1036
FT /evidence="ECO:0007829|PDB:2N11"
FT HELIX 1038..1040
FT /evidence="ECO:0007829|PDB:2N11"
FT HELIX 1055..1066
FT /evidence="ECO:0007829|PDB:2N11"
FT HELIX 1076..1078
FT /evidence="ECO:0007829|PDB:6E5N"
FT TURN 1079..1083
FT /evidence="ECO:0007829|PDB:6E5N"
FT HELIX 1091..1100
FT /evidence="ECO:0007829|PDB:2N0Z"
FT HELIX 1104..1118
FT /evidence="ECO:0007829|PDB:2N0Z"
FT HELIX 1168..1172
FT /evidence="ECO:0007829|PDB:6J56"
FT STRAND 1177..1183
FT /evidence="ECO:0007829|PDB:6J56"
FT STRAND 1201..1207
FT /evidence="ECO:0007829|PDB:6J56"
FT STRAND 1210..1217
FT /evidence="ECO:0007829|PDB:6J56"
FT STRAND 1224..1227
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1232..1234
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1240..1243
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1245..1247
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1255..1264
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1267..1276
FT /evidence="ECO:0007829|PDB:6J56"
FT HELIX 1284..1289
FT /evidence="ECO:0007829|PDB:6J56"
SQ SEQUENCE 1294 AA; 149691 MW; 3A8966E6864B8576 CRC64;
MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE
DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL
GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD
RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK
EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY
LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG
GCNLKNKSAQ SLEYCAELLG LDQDDLRVSL TTRVMLTTAG GTKGTVIKVP LKVEQANNAR
DALAKTVYSH LFDHVVNRVN QCFPFETSSY FIGVLDIAGF EYFEHNSFEQ FCINYCNEKL
QQFFNERILK EEQELYQKEG LGVNEVHYVD NQDCIDLIEA KLVGILDILD EENRLPQPSD
QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA
LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS
TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK
YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL
VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL
VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD
ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM
EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE
AELISDEAQA DLALRRSLDS YPVSKNDGTR PKMTPEQMAK EMSEFLSRGP AVLATKAAAG
TKKYDLSKWK YAELRDTINT SCDIELLAAC REEFHRRLKV YHAWKSKNKK RNTETEQRAP
KSVTDYDFAP FLNNSPQQNP AAQIPARQRE IEMNRQQRFF RIPFIRPADQ YKDPQSKKKG
WWYAHFDGPW IARQMELHPD KPPILLVAGK DDMEMCELNL EETGLTRKRG AEILPRQFEE
IWERCGGIQY LQNAIESRQA RPTYATAMLQ SLLK
