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 27-MAR-2024, entry version 224. 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 FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TOM1 AND TOM1L2, AND RP MUTAGENESIS OF 1116-ARG--LEU-1118. RX PubMed=23023224; DOI=10.1038/ncb2589; RA Tumbarello D.A., Waxse B.J., Arden S.D., Bright N.A., Kendrick-Jones J., RA Buss F.; RT "Autophagy receptors link myosin VI to autophagosomes to mediate Tom1- RT dependent autophagosome maturation and fusion with the lysosome."; RL Nat. Cell Biol. 14:1024-1035(2012). RN [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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). RN [26] {ECO:0007744|PDB:6J56} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1166-1294 IN COMPLEX WITH TOM1, RP FUNCTION, AND INTERACTION WITH TOM1; TAX1BP1; CALCOCO2/NDP52 AND OPTN. RX PubMed=31371777; DOI=10.1038/s41467-019-11481-6; RA Hu S., Guo Y., Wang Y., Li Y., Fu T., Zhou Z., Wang Y., Liu J., Pan L.; RT "Structure of Myosin VI/Tom1 complex reveals a cargo recognition mode of RT Myosin VI for tethering."; RL Nat. Commun. 10:3459-3459(2019). 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). Together with TOM1, mediates delivery of endocytic CC cargo to autophagosomes thereby promoting autophagosome maturation and CC driving fusion with lysosomes (PubMed:23023224). Links TOM1 with CC autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN CC (PubMed:31371777). 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:23023224, CC ECO:0000269|PubMed:29467281, ECO:0000269|PubMed:31371777}. 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 CABP5 (By similarity). Interacts with CC TOM1 (PubMed:23023224, PubMed:31371777). Interacts with OPTN CC (PubMed:31371777). Interacts with TAX1BP1 and CALCOCO2/NDP52 CC (PubMed:31371777). Interacts with TOM1L2 (PubMed:23023224). CC {ECO:0000250|UniProtKB:E1BPK6, ECO:0000250|UniProtKB:Q29122, CC ECO:0000250|UniProtKB:Q64331, ECO:0000250|UniProtKB:Q9I8D1, CC ECO:0000269|PubMed:11967127, ECO:0000269|PubMed:15044955, CC ECO:0000269|PubMed:15247260, ECO:0000269|PubMed:23023224, CC ECO:0000269|PubMed:29467281, ECO:0000269|PubMed:31371777}. CC -!- INTERACTION: CC Q9UM54; P98082: DAB2; NbExp=3; IntAct=EBI-350606, EBI-1171238; CC Q9UM54; Q96II8: LRCH3; NbExp=3; IntAct=EBI-350606, EBI-8795942; 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; Q96II8: LRCH3; NbExp=3; IntAct=EBI-15706115, EBI-8795942; 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}. Cytoplasmic vesicle, autophagosome CC {ECO:0000269|PubMed:23023224}. Endosome {ECO:0000269|PubMed:23023224}. CC Note=Also present in endocyctic vesicles (PubMed:16507995). CC Translocates from membrane ruffles, endocytic vesicles and cytoplasm to CC Golgi apparatus, perinuclear membrane and nucleus through induction by CC p53 and p53-induced DNA damage (PubMed:16507995). Recruited into CC membrane ruffles from cell surface by EGF-stimulation (PubMed:9852149). CC Colocalizes with DAB2 in clathrin-coated pits/vesicles CC (PubMed:11967127). Colocalizes with OPTN at the Golgi complex and in CC vesicular structures close to the plasma membrane (By similarity). CC Recruited to endosomes by TOM1 and TOM1L2 (PubMed:23023224). CC {ECO:0000250|UniProtKB:Q9I8D1, ECO:0000269|PubMed:11967127, CC ECO:0000269|PubMed:16507995, ECO:0000269|PubMed:23023224, 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 conferring 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 CCDS; CCDS93950.1; -. [Q9UM54-5] 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; 381. DR ComplexPortal; CPX-7724; LIFT actin modulation complex. DR ComplexPortal; CPX-7725; DISP septin regulator complex. DR DIP; DIP-33123N; -. DR IntAct; Q9UM54; 246. DR MINT; Q9UM54; -. DR STRING; 9606.ENSP00000358994; -. DR GlyGen; Q9UM54; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000358994; -. DR PeptideAtlas; 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 Pumba; Q9UM54; -. DR Antibodypedia; 4385; 163 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 AGR; HGNC:7605; -. 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; 228012; Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome. DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA31410; -. DR VEuPathDB; HostDB:ENSG00000196586; -. DR eggNOG; KOG0163; Eukaryota. DR GeneTree; ENSGT00940000156078; -. DR InParanoid; Q9UM54; -. DR OMA; MIDHEFE; -. 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; 13 hits in 1162 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 196 other cell types or tissues. DR ExpressionAtlas; Q9UM54; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central. DR GO; GO:0005884; C:actin filament; ISS:UniProtKB. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. 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:0005768; C:endosome; IEA:UniProtKB-SubCell. 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; IEA:UniProtKB-SubCell. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. 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: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:0051046; P:regulation of secretion; IMP:UniProtKB. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. 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; cd21759; CBD_MYO6-like; 1. DR CDD; cd22294; MYO6_MIU_linker; 1. DR CDD; cd01382; MYSc_Myo6; 1. DR CDD; cd21958; MyUb_Myo6; 1. DR Gene3D; 1.10.10.820; -; 1. DR Gene3D; 1.20.58.530; -; 1. DR Gene3D; 3.30.70.1590; -; 1. DR Gene3D; 6.10.220.10; -; 1. DR Gene3D; 3.40.850.10; Kinesin motor domain; 2. DR Gene3D; 2.30.30.360; Myosin S1 fragment, N-terminal; 1. DR Gene3D; 1.20.120.720; Myosin VI head, motor domain, U50 subdomain; 1. DR InterPro; IPR036961; Kinesin_motor_dom_sf. DR InterPro; IPR049016; MYO6_lever. 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 PANTHER; PTHR13140; MYOSIN; 1. DR PANTHER; PTHR13140:SF745; UNCONVENTIONAL MYOSIN-VI; 1. DR Pfam; PF21521; MYO6_lever; 1. 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; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51456; MYOSIN_MOTOR; 1. DR PROSITE; PS51844; SH3_LIKE; 1. DR Genevisible; Q9UM54; HS. 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; Endosome; Golgi apparatus; Hearing; Membrane; Motor protein; KW Myosin; Non-syndromic deafness; Nucleotide-binding; Nucleus; KW Phosphoprotein; 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 1060..1285 FT /note="Interaction with TAX1BP1 and CALCOCO2/NDP52" FT /evidence="ECO:0000269|PubMed:31371777" FT REGION 1116..1118 FT /note="Interaction with OPTN" FT /evidence="ECO:0000250|UniProtKB:Q9I8D1" FT REGION 1157..1285 FT /note="Interaction with TOM1" FT /evidence="ECO:0000269|PubMed:31371777" 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 MUTAGEN 1116..1118 FT /note="RRL->AAA: Decreased localization to autophagosomes." FT /evidence="ECO:0000269|PubMed:23023224" 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 //