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Database: UniProt
Entry: Q9UM54
LinkDB: Q9UM54
Original site: Q9UM54 
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   22-JUL-2015, entry version 157.
DE   RecName: Full=Unconventional myosin-VI;
DE   AltName: Full=Unconventional myosin-6;
GN   Name=MYO6; Synonyms=KIAA0389;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Skvorak A.B., Morton C.C., Copeland N.G., Jenkins N.A.;
RT   "Characterization of unconventional MYO6, the human homologue of the
RT   gene 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
RT   gene 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.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for 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.,
RA   Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA   Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA   Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA   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.,
RA   Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA   Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA   Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA   Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA   Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA   Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA   Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA   Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA   McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA   Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA   Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA   Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA   Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA   Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA   Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA   Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA   Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA   Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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.,
RA   Yamashita R., Yamamoto J., Sekine M., Tsuritani K., Wakaguri H.,
RA   Ishii S., Sugiyama T., Saito K., Isono Y., Irie R., Kushida N.,
RA   Yoneyama T., Otsuka R., Kanda K., Yokoi T., Kondo H., Wagatsuma M.,
RA   Murakawa K., Ishida S., Ishibashi T., Takahashi-Fujii A., Tanase T.,
RA   Nagai K., Kikuchi H., Nakai K., Isogai T., Sugano S.;
RT   "Diversification of transcriptional modulation: large-scale
RT   identification and characterization of putative alternative promoters
RT   of human genes.";
RL   Genome Res. 16:55-65(2006).
RN   [9]
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   [10]
RP   FUNCTION IN ENDOCYTOSIS, SUBCELLULAR LOCATION, AND ALTERNATIVE
RP   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
RT   in clathrin-mediated endocytosis.";
RL   EMBO J. 20:3676-3684(2001).
RN   [11]
RP   INTERACTION WITH DAB2.
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
RT   receptor-mediated endocytosis and the actin cytoskeleton.";
RL   Traffic 3:331-341(2002).
RN   [12]
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   [13]
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   [14]
RP   FUNCTION.
RX   PubMed=16949370; DOI=10.1016/j.molcel.2006.07.005;
RA   Vreugde S., Ferrai C., Miluzio A., Hauben E., Marchisio P.C.,
RA   Crippa M.P., Bussi M., Biffo S.;
RT   "Nuclear myosin VI enhances RNA polymerase II-dependent
RT   transcription.";
RL   Mol. Cell 23:749-755(2006).
RN   [15]
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   [16]
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
RT   structure and function of myosin VI.";
RL   Nat. Struct. Mol. Biol. 15:591-597(2008).
RN   [17]
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.,
RA   Buerckstuemmer T., 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   [18]
RP   SAH DOMAIN.
RX   PubMed=25122759; DOI=10.1074/jbc.M114.585679;
RA   Wolny M., Batchelor M., Knight P.J., Paci E., Dougan L., Peckham M.;
RT   "Stable single alpha-helices are constant force springs in proteins.";
RL   J. Biol. Chem. 289:27825-27835(2014).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-405, AND IDENTIFICATION
RP   BY 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [20]
RP   VARIANT DFNA22 TYR-442.
RX   PubMed=11468689; DOI=10.1086/323156;
RA   Melchionda S., Ahituv N., Bisceglia L., Sobe T., Glaser F.,
RA   Rabionet R., Arbones M.L., Notarangelo A., Di Iorio E., Carella M.,
RA   Zelante L., Estivill X., Avraham K.B., Gasparini P.;
RT   "MYO6, the human homologue of the gene responsible for deafness in
RT   Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic
RT   hearing loss.";
RL   Am. J. Hum. Genet. 69:635-640(2001).
RN   [21]
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.,
RA   Ahmad M.M., Mohiddin S.A., Fananapazir L., Caruso R.C., Husnain T.,
RA   Khan S.N., 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   [22]
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
RT   deafness, 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
CC       activity. Unconventional myosins serve in intracellular movements.
CC       Myosin 6 is a reverse-direction motor protein that moves towards
CC       the minus-end of actin filaments. Has slow rate of actin-activated
CC       ADP release due to weak ATP binding. Functions in a variety of
CC       intracellular processes such as vesicular membrane trafficking and
CC       cell migration. Required for the structural integrity of the Golgi
CC       apparatus via the p53-dependent pro-survival pathway. Appears to
CC       be involved in a very early step of clathrin-mediated endocytosis
CC       in polarized epithelial cells. May act as a regulator of F-actin
CC       dynamics. May play a role in transporting DAB2 from the plasma
CC       membrane to specific cellular targets. Required for structural
CC       integrity of inner ear hair cells (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer; dimerization seems to implicate the unfolding
CC       of the three-helix bundle region creating an additional calmodulin
CC       binding site, and cargo binding (By similarity). Binding to
CC       calmodulin through a unique insert, not found in other myosins,
CC       located in the neck region between the motor domain and the IQ
CC       domain appears to contribute to the directionality reversal. This
CC       interaction occurs only if the C-terminal lobe of calmodulin is
CC       occupied by calcium. Interaction with F-actin/ACTN1 occurs only at
CC       the apical brush border domain of the proximal tubule cells (By
CC       similarity). Interacts with DAB2. In vitro, the C-terminal
CC       globular tail binds a C-terminal region of DAB2. Interacts with
CC       CFTR. Forms a complex with CFTR and DAB2 in the apical membrane of
CC       epithelial cells. Interacts with OPTN (By similarity).
CC       {ECO:0000250, ECO:0000250|UniProtKB:Q29122}.
CC   -!- INTERACTION:
CC       P98082:DAB2; NbExp=3; IntAct=EBI-350606, EBI-1171238;
CC       P98078:Dab2 (xeno); NbExp=4; IntAct=EBI-350606, EBI-1391846;
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC       membrane; Peripheral membrane protein. Golgi apparatus
CC       {ECO:0000250}. Nucleus. Cytoplasm, perinuclear region. Membrane,
CC       clathrin-coated pit. Cell projection, ruffle membrane; Peripheral
CC       membrane protein. Note=Also present in endocyctic vesicles, and
CC       membrane ruffles. Translocates from membrane ruffles, endocytic
CC       vesicles and cytoplasm to Golgi apparatus, perinuclear membrane
CC       and nucleus through induction by p53 and p53-induced DNA damage.
CC       Recruited into membrane ruffles from cell surface by EGF-
CC       stimulation. Colocalizes with DAB2 in clathrin-coated
CC       pits/vesicles. Colocalizes with OPTN at the Golgi complex and in
CC       vesicular structures close to the plasma membrane (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasmic vesicle, clathrin-
CC       coated vesicle membrane.
CC   -!- SUBCELLULAR LOCATION: Isoform 4: Cytoplasmic vesicle, clathrin-
CC       coated vesicle membrane. Cell projection, ruffle membrane.
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
CC       heart, brain, placenta, pancreas, spleen, thymus, prostate,
CC       testis, ovary, small intestine and colon. Highest levels in brain,
CC       pancreas, testis and small intestine. Also expressed in fetal
CC       brain and cochlea. Isoform 1 and isoform 2, containing the small
CC       insert, and isoform 4, containing neither insert, are expressed in
CC       unpolarized epithelial cells. {ECO:0000269|PubMed:9259267}.
CC   -!- DOMAIN: Divided into three regions: a N-terminal motor (head)
CC       domain, followed by a neck domain consisting of a calmodulin-
CC       binding linker domain and a single IQ motif, and a C-terminal tail
CC       region with a three-helix bundle region, a SAH domain and a unique
CC       globular domain required for interaction with other proteins such
CC       as cargo-binding. {ECO:0000305}.
CC   -!- DOMAIN: The SAH (single alpha-helix) region is characterized by a
CC       high content of charged residues which are predicted to stabilize
CC       the alpha-helical structure by ionic bonds. Its contribution to
CC       the mechanism confering the myosin movement on actin filaments is
CC       debated. {ECO:0000250|UniProtKB:Q9UM54,
CC       ECO:0000305|PubMed:25122759}.
CC   -!- PTM: Phosphorylation in the motor domain, induced by EGF, results
CC       in translocation of MYO6 from the cell surface to membrane ruffles
CC       and affects F-actin dynamics. Phosphorylated in vitro by p21-
CC       activated kinase (PAK) (By similarity). {ECO:0000250}.
CC   -!- DISEASE: Deafness, autosomal dominant, 22 (DFNA22) [MIM:606346]: A
CC       form of non-syndromic sensorineural hearing loss. Sensorineural
CC       deafness results from damage to the neural receptors of the inner
CC       ear, the nerve pathways to the brain, or the area of the brain
CC       that receives sound information. DFNA22 is progressive and
CC       postlingual, with onset during childhood. By the age of
CC       approximately 50 years, affected individuals invariably have
CC       profound sensorineural deafness. {ECO:0000269|PubMed:11468689}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Deafness, autosomal recessive, 37 (DFNB37) [MIM:607821]:
CC       A form of non-syndromic sensorineural hearing loss. Sensorineural
CC       deafness results from damage to the neural receptors of the inner
CC       ear, the nerve pathways to the brain, or the area of the brain
CC       that receives sound information. {ECO:0000269|PubMed:12687499}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Deafness, sensorineural, with hypertrophic cardiomyopathy
CC       (DFNHCM) [MIM:606346]: An autosomal dominant sensorineural
CC       deafness associated with hypertrophic cardiomyopathy.
CC       {ECO:0000269|PubMed:15060111}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC       superfamily. Myosin family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 IQ domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 myosin motor domain. {ECO:0000305}.
CC   -!- CAUTION: Represents an unconventional myosin. This protein should
CC       not be confused with the conventional myosin-6 (MYH6).
CC       {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=Translation N-terminally shortened.; 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; CAI19520.1; -; Genomic_DNA.
DR   EMBL; AL136093; CAI19520.1; JOINED; Genomic_DNA.
DR   EMBL; AL109897; CAI19521.1; -; Genomic_DNA.
DR   EMBL; AL136093; CAI19521.1; JOINED; Genomic_DNA.
DR   EMBL; AL109897; CAI19522.1; -; Genomic_DNA.
DR   EMBL; AL136093; CAI19522.1; JOINED; Genomic_DNA.
DR   EMBL; AL136093; CAI42824.1; -; Genomic_DNA.
DR   EMBL; AL109897; CAI42824.1; JOINED; Genomic_DNA.
DR   EMBL; AL136093; CAI42825.1; -; Genomic_DNA.
DR   EMBL; AL109897; CAI42825.1; JOINED; Genomic_DNA.
DR   EMBL; AL136093; CAI42826.1; -; Genomic_DNA.
DR   EMBL; AL109897; CAI42826.1; JOINED; 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   UniGene; Hs.149387; -.
DR   ProteinModelPortal; Q9UM54; -.
DR   SMR; Q9UM54; 2-922, 1175-1277.
DR   BioGrid; 110730; 34.
DR   DIP; DIP-33123N; -.
DR   IntAct; Q9UM54; 15.
DR   MINT; MINT-239443; -.
DR   STRING; 9606.ENSP00000358994; -.
DR   PhosphoSite; Q9UM54; -.
DR   BioMuta; MYO6; -.
DR   DMDM; 122065628; -.
DR   MaxQB; Q9UM54; -.
DR   PaxDb; Q9UM54; -.
DR   PRIDE; Q9UM54; -.
DR   Ensembl; ENST00000369977; ENSP00000358994; ENSG00000196586. [Q9UM54-1]
DR   Ensembl; ENST00000369985; ENSP00000359002; ENSG00000196586. [Q9UM54-2]
DR   Ensembl; ENST00000615563; ENSP00000478013; ENSG00000196586. [Q9UM54-2]
DR   GeneID; 4646; -.
DR   KEGG; hsa:4646; -.
DR   UCSC; uc003pig.1; human. [Q9UM54-5]
DR   UCSC; uc003pih.1; human. [Q9UM54-1]
DR   UCSC; uc003pii.1; human. [Q9UM54-2]
DR   CTD; 4646; -.
DR   GeneCards; GC06P076515; -.
DR   GeneReviews; MYO6; -.
DR   HGNC; HGNC:7605; MYO6.
DR   HPA; CAB010762; -.
DR   HPA; HPA035483; -.
DR   MIM; 600970; gene.
DR   MIM; 606346; phenotype.
DR   MIM; 607821; phenotype.
DR   neXtProt; NX_Q9UM54; -.
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.
DR   PharmGKB; PA31410; -.
DR   eggNOG; COG5022; -.
DR   GeneTree; ENSGT00800000124053; -.
DR   HOVERGEN; HBG003523; -.
DR   InParanoid; Q9UM54; -.
DR   KO; K10358; -.
DR   OrthoDB; EOG7TQTZZ; -.
DR   PhylomeDB; Q9UM54; -.
DR   TreeFam; TF351449; -.
DR   Reactome; REACT_11035; Gap junction degradation.
DR   Reactome; REACT_18307; Trafficking of AMPA receptors.
DR   ChiTaRS; MYO6; human.
DR   GeneWiki; MYO6; -.
DR   GenomeRNAi; 4646; -.
DR   NextBio; 17908; -.
DR   PRO; PR:Q9UM54; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   Bgee; Q9UM54; -.
DR   CleanEx; HS_MYO6; -.
DR   ExpressionAtlas; Q9UM54; baseline and differential.
DR   Genevisible; Q9UM54; HS.
DR   GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR   GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016591; C:DNA-directed RNA polymerase II, holoenzyme; IDA:UniProtKB.
DR   GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0031941; C:filamentous actin; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
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; TAS:Reactome.
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:0060001; F:minus-end directed microfilament motor activity; NAS:UniProtKB.
DR   GO; GO:0003774; F:motor activity; ISS:UniProtKB.
DR   GO; GO:0030048; P:actin filament-based movement; ISS:UniProtKB.
DR   GO; GO:0042491; P:auditory receptor cell differentiation; IEA:Ensembl.
DR   GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR   GO; GO:0016358; P:dendrite development; IEA:Ensembl.
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:0014047; P:glutamate secretion; IEA:Ensembl.
DR   GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR   GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR   GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR   GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR   GO; GO:0008152; P:metabolic process; ISS:GOC.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR   GO; GO:0006605; P:protein targeting; IEA:Ensembl.
DR   GO; GO:0051046; P:regulation of secretion; IMP:UniProtKB.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR   GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR   GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR   GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   InterPro; IPR001609; Myosin_head_motor_dom.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   Pfam; PF00063; Myosin_head; 1.
DR   PRINTS; PR00193; MYOSINHEAVY.
DR   SMART; SM00015; IQ; 1.
DR   SMART; SM00242; MYSc; 1.
DR   SUPFAM; SSF52540; SSF52540; 2.
DR   PROSITE; PS51456; MYOSIN_MOTOR; 1.
PE   1: Evidence at protein level;
KW   Actin-binding; Alternative splicing; ATP-binding; Calmodulin-binding;
KW   Cardiomyopathy; Cell membrane; Cell projection; Coated pit;
KW   Complete proteome; Cytoplasm; Cytoplasmic vesicle; Deafness;
KW   Disease mutation; Endocytosis; Golgi apparatus; Hearing; Membrane;
KW   Motor protein; Myosin; Non-syndromic deafness; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW   Transport.
FT   CHAIN         1   1294       Unconventional myosin-VI.
FT                                /FTId=PRO_0000123464.
FT   DOMAIN       57    771       Myosin motor.
FT   DOMAIN      814    834       IQ.
FT   NP_BIND     151    158       ATP. {ECO:0000255}.
FT   REGION      273    317       Responsible for slow ATPase activity.
FT                                {ECO:0000250}.
FT   REGION      665    672       Actin-binding. {ECO:0000255}.
FT   REGION      782    810       Required for binding calmodulin.
FT                                {ECO:0000250}.
FT   REGION      835    916       Three-helix bundle.
FT   REGION      917    984       SAH. {ECO:0000305|PubMed:25122759}.
FT   REGION     1116   1118       Interaction with OPTN.
FT   COMPBIAS    920   1027       Glu-rich.
FT   MOD_RES     405    405       Phosphothreonine.
FT                                {ECO:0000269|PubMed:24275569}.
FT   VAR_SEQ    1037   1068       Missing (in isoform 2 and isoform 5).
FT                                {ECO:0000303|PubMed:9259267}.
FT                                /FTId=VSP_007985.
FT   VAR_SEQ    1037   1045       Missing (in isoform 1).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:9205841}.
FT                                /FTId=VSP_022332.
FT   VAR_SEQ    1147   1156       DFAPFLNNSP -> A (in isoform 6).
FT                                {ECO:0000303|PubMed:16344560}.
FT                                /FTId=VSP_042208.
FT   VAR_SEQ    1147   1155       Missing (in isoform 4 and isoform 5).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_022333.
FT   VARIANT     216    216       E -> V (in DFNB37; dbSNP:rs28936390).
FT                                {ECO:0000269|PubMed:12687499}.
FT                                /FTId=VAR_016209.
FT   VARIANT     246    246       H -> R (in DFNHCM; dbSNP:rs28936391).
FT                                {ECO:0000269|PubMed:15060111}.
FT                                /FTId=VAR_029988.
FT   VARIANT     442    442       C -> Y (in DFNA22).
FT                                {ECO:0000269|PubMed:11468689}.
FT                                /FTId=VAR_012110.
FT   CONFLICT   1156   1156       P -> A (in Ref. 5; CAI42826).
FT                                {ECO:0000305}.
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
//
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