Reviewed,
UniProtKB/Swiss-Prot Q9UM54 (MYO6_HUMAN)
Last modified
November 3, 2009.
Version 98.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Myosin-VI Alternative name(s): Unconventional myosin VI | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1294 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells By similarity. |
| Subunit structure | Homodimer. Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal. This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium. Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells By similarity. Interacts with DAB2. In vitro, the C-terminal globular tail binds a C-terminal region of DAB2. Interacts with CFTR. Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells. |
| Subcellular location | Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Nucleus. Cytoplasm › perinuclear region. Membrane › clathrin-coated pit. Cell projection › ruffle membrane; Peripheral membrane protein. Note: Also present in endocyctic vesicles, and membrane ruffles. Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage. Recruited into membrane ruffles from cell surface by EGF-stimulation. Colocalizes with DAB2 in clathrin-coated pits/vesicles. Ref.7 Ref.12 Isoform 3: Cytoplasmic vesicle › clathrin-coated vesicle membrane. Ref.7 Ref.12 Isoform 4: Cytoplasmic vesicle › clathrin-coated vesicle membrane. Cell projection › ruffle membrane. Ref.7 Ref.12 |
| Tissue specificity | Expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in brain, pancreas, testis and small intestine. Also expressed in fetal brain and cochlea. Isoform 1 and isoform 2, containing the small insert, and isoform 4, containing neither insert, are expressed in unpolarized epithelial cells. Ref.1 |
| Domain | Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a coiled-coil and a unique globular domain required for interaction with other proteins. |
| Post-translational modification | Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK) By similarity. |
| Involvement in disease | Defects in MYO6 are the cause of non-syndromic sensorineural deafness autosomal dominant type 22 (DFNA22) [MIM:606346]. DFNA22 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA22 is progressive and postlingual, with onset during childhood. By the age of approximately 50 years, affected individuals invariably have profound sensorineural deafness. Ref.13 Defects in MYO6 are the cause of non-syndromic sensorineural deafness autosomal recessive type 37 (DFNB37) [MIM:607821]. Defects in MYO6 are the cause of sensorineural deafness with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346]. Ref.15 |
| Sequence similarities | Contains 1 IQ domain. Contains 1 myosin head-like domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| GIPC1 | O14908 | 1 | EBI-350606,EBI-373132 | |
| RPS27A | P62988 | 1 | EBI-350606,EBI-413034 |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 3 (identifier: Q9UM54-3) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 1 (identifier: Q9UM54-1) The sequence of this isoform differs from the canonical sequence as follows: 1037-1045: Missing. | ||||||
| Isoform 2 (identifier: Q9UM54-2) The sequence of this isoform differs from the canonical sequence as follows: 1037-1068: Missing. | ||||||
| Isoform 4 (identifier: Q9UM54-4) The sequence of this isoform differs from the canonical sequence as follows: 1147-1155: Missing. | ||||||
| Isoform 5 (identifier: Q9UM54-5) The sequence of this isoform differs from the canonical sequence as follows: 1037-1068: Missing. 1147-1155: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1294 | 1294 | Myosin-VI | PRO_0000123464 | |||||
Regions | |||||||||
| Domain | 1 – 759 | 759 | Myosin head-like | ||||||
| Domain | 814 – 834 | 21 | IQ | ||||||
| Nucleotide binding | 151 – 158 | 8 | ATP Potential | ||||||
| Region | 273 – 317 | 45 | Responsible for slow ATPase activity By similarity | ||||||
| Region | 665 – 672 | 8 | Actin-binding Potential | ||||||
| Region | 782 – 810 | 29 | Required for binding calmodulin By similarity | ||||||
| Coiled coil | 864 – 1023 | 160 | Potential | ||||||
| Compositional bias | 920 – 1027 | 108 | Glu-rich | ||||||
Amino acid modifications | |||||||||
| Modified residue | 405 | 1 | Phosphothreonine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1037 – 1068 | 32 | Missing in isoform 2 and isoform 5. | VSP_007985 | |||||
| Alternative sequence | 1037 – 1045 | 9 | Missing in isoform 1. | VSP_022332 | |||||
| Alternative sequence | 1147 – 1155 | 9 | Missing in isoform 4 and isoform 5. | VSP_022333 | |||||
| Natural variant | 216 | 1 | E → V in DFNB37. Ref.14 | VAR_016209 | |||||
| Natural variant | 246 | 1 | H → R in DFNHCM. Ref.15 | VAR_029988 | |||||
| Natural variant | 442 | 1 | C → Y in DFNA22. Ref.13 | VAR_012110 | |||||
Experimental info | |||||||||
| Sequence conflict | 1156 | 1 | P → A in CAI42826. Ref.5 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice." Avraham K.B., Hasson T., Sobe T., Balsara B., Testa J.R., Skvorak A.B., Morton C.C., Copeland N.G., Jenkins N.A. Hum. Mol. Genet. 6:1225-1231(1997) [PubMed: 9259267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Brain. |
| [2] | Avraham K.B. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [3] | "Genomic organization of the human myosin VI gene (MYO6), a candidate gene for neurosensory and storage disorders." Kuehn M.H., Hageman G.S. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [5] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 5). |
| [6] | "Myosin VI is an actin-based motor that moves backwards." Wells A.L., Lin A.W., Chen L.-Q., Safer D., Cain S.M., Hasson T., Carragher B.O., Milligan R.A., Sweeney H.L. Nature 401:505-508(1999) [PubMed: 10519557] [Abstract] Cited for: FUNCTION. |
| [7] | "Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis." Buss F., Arden S.D., Lindsay M., Luzio J.P., Kendrick-Jones J. EMBO J. 20:3676-3684(2001) [PubMed: 11447109] [Abstract] Cited for: FUNCTION IN ENDOCYTOSIS, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING. |
| [8] | "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton." Morris S.M., Arden S.D., Roberts R.C., Kendrick-Jones J., Cooper J.A., Luzio J.P., Buss F. Traffic 3:331-341(2002) [PubMed: 11967127] [Abstract] Cited for: INTERACTION WITH DAB2. |
| [9] | "Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator." Swiatecka-Urban A., Boyd C., Coutermarsh B., Karlson K.H., Barnaby R., Aschenbrenner L., Langford G.M., Hasson T., Stanton B.A. J. Biol. Chem. 279:38025-38031(2004) [PubMed: 15247260] [Abstract] Cited for: INTERACTION WITH CFTR. |
| [10] | "A monomeric myosin VI with a large working stroke." Lister I., Schmitz S., Walker M., Trinick J., Buss F., Veigel C., Kendrick-Jones J. EMBO J. 23:1729-1738(2004) [PubMed: 15044955] [Abstract] Cited for: SUBUNIT. |
| [11] | "Nuclear myosin VI enhances RNA polymerase II-dependent transcription." Vreugde S., Ferrai C., Miluzio A., Hauben E., Marchisio P.C., Crippa M.P., Bussi M., Biffo S. Mol. Cell 23:749-755(2006) [PubMed: 16949370] [Abstract] Cited for: FUNCTION. |
| [12] | "Myosin VI is a mediator of the p53-dependent cell survival pathway." Jung E.J., Liu G., Zhou W., Chen X. Mol. Cell. Biol. 26:2175-2186(2006) [PubMed: 16507995] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. |
| [13] | "MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss." Melchionda S., Ahituv N., Bisceglia L., Sobe T., Glaser F., Rabionet R., Arbones M.L., Notarangelo A., Di Iorio E., Carella M., Zelante L., Estivill X., Avraham K.B., Gasparini P. Am. J. Hum. Genet. 69:635-640(2001) [PubMed: 11468689] [Abstract] Cited for: VARIANT DFNA22 TYR-442. |
| [14] | "Mutations of MYO6 are associated with recessive deafness, DFNB37." Ahmed Z.M., Morell R.J., Riazuddin S., Gropman A., Shaukat S., Ahmad M.M., Mohiddin S.A., Fananapazir L., Caruso R.C., Husnain T., Khan S.N., Riazuddin S., Griffith A.J., Friedman T.B., Wilcox E.R. Am. J. Hum. Genet. 72:1315-1322(2003) [PubMed: 12687499] [Abstract] Cited for: VARIANT DFNB37 VAL-216. |
| [15] | "Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6)." Mohiddin S.A., Ahmed Z.M., Griffith A.J., Tripodi D., Friedman T.B., Fananapazir L., Morell R.J. J. Med. Genet. 41:309-314(2004) [PubMed: 15060111] [Abstract] Cited for: VARIANT DFNHCM ARG-246. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U90236 mRNA. Translation: AAC51654.2. AF229111 AF229110 Genomic DNA. Translation: AAK00229.1. AL109897, AL136093 Genomic DNA. Translation: CAI19520.1. AL109897, AL136093 Genomic DNA. Translation: CAI19521.1. AL109897, AL136093 Genomic DNA. Translation: CAI19522.1. AL136093, AL109897 Genomic DNA. Translation: CAI42824.1. AL136093, AL109897 Genomic DNA. Translation: CAI42825.1. AL136093, AL109897 Genomic DNA. Translation: CAI42826.1. AB002387 mRNA. Translation: BAA20843.2. Different initiation. | |
| IPI | IPI00008455. IPI00069126. IPI00642722. IPI00816452. IPI00816461. |
| RefSeq | NP_004990.3. |
| UniGene | Hs.149387 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1MND based on UniProtKB P08799. |
| SMR | Q9UM54. Positions 4-812. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9UM54. 10 interactions. |
| STRING | Q9UM54. |
PTM databases | |
| PhosphoSite | Q9UM54. |
Proteomic databases | |
| PRIDE | Q9UM54. |
Genome annotation databases | |
| Ensembl | ENST00000369975; ENSP00000358992; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369977; ENSP00000358994; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369978; ENSP00000358995; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369981; ENSP00000358998; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369985; ENSP00000359002; ENSG00000196586; Homo sapiens. [Genome view] ENST00000428345; ENSP00000412500; ENSG00000196586; Homo sapiens. [Genome view] ENST00000430435; ENSP00000399406; ENSG00000196586; Homo sapiens. [Genome view] |
| GeneID | 4646. |
| KEGG | hsa:4646. |
| UCSC | uc003pig.1. human. uc003pih.1. human. uc003pii.1. human. |
Organism-specific databases | |
| CTD | 4646. |
| GeneCards | GC06P076515. |
| H-InvDB | HIX0006018. |
| HGNC | HGNC:7605. MYO6. |
| HPA | CAB010762. |
| MIM | 600970. gene. 606346. phenotype. 607821. phenotype. |
| Orphanet | 99739. Cardiomyopathy, familial, hypertrophic. 90635. Deafness, autosomal dominant, nonsyndromic, sensorineural, type DFNA. 90636. Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB. |
| PharmGKB | PA31410. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q9UM54. |
| HOVERGEN | Q9UM54. |
| OMA | TINTSCD. |
Enzyme and pathway databases | |
| Reactome | REACT_13685. Synaptic Transmission. REACT_9480. Gap junction trafficking and regulation. |
Gene expression databases | |
| ArrayExpress | Q9UM54. |
| Bgee | Q9UM54. |
| CleanEx | HS_MYO6. |
| Genevestigator | Q9UM54. |
| GermOnline | ENSG00000196586. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000048. IQ_CaM_bd_region. IPR001609. Myosin_head. [Graphical view] |
| Pfam | PF00612. IQ. 1 hit. PF00063. Myosin_head. 1 hit. [Graphical view] |
| PRINTS | PR00193. MYOSINHEAVY. |
| ProDom | PD000355. Myosin_head. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00015. IQ. 1 hit. SM00242. MYSc. 1 hit. [Graphical view] |
| PROSITE | PS50096. IQ. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 17908. |
| SOURCE | Search... |
Entry information
| Entry name | MYO6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UM54 Secondary accession number(s): Q5TEM5 Q9UEG2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


