Unconventional myosin-VI

MYO6
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2N11, 2N13, 2N0Z, 2N10, 2N12
Identifiers
Aliases	MYO6, DFNA22, DFNB37, myosin VI, Myo6-008, Myo6-007
External IDs	OMIM: 600970; MGI: 104785; HomoloGene: 56417; GeneCards: MYO6; OMA:MYO6 - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	75,919,537 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	80,219,011 bp
RNA expression pattern
	Top expressed in
	amniotic fluid; ; internal globus pallidus; ; corpus callosum; ; sural nerve; ; external globus pallidus; ; pancreatic ductal cell; ; inferior ganglion of vagus nerve; ; pars reticulata; ; subthalamic nucleus; ; renal medulla;
	Top expressed in
	olfactory epithelium; ; neural layer of retina; ; yolk sac; ; right kidney; ; human kidney; ; utricle; ; epithelium of small intestine; ; ileum; ; Ileal epithelium; ; vestibular sensory epithelium;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	cytoskeletal motor activity; actin filament binding; ATP binding; calmodulin binding; protein binding; minus-end directed microfilament motor activity; ADP binding; actin binding; nucleotide binding; cadherin binding; identical protein binding;
Cellular component	myosin complex; nucleus; intracellular membrane-bounded organelle; cell projection; ruffle membrane; RNA polymerase II, holoenzyme; nucleoplasm; lysosomal membrane; perinuclear region of cytoplasm; clathrin-coated endocytic vesicle; apical part of cell; clathrin-coated vesicle membrane; ruffle; cytosol; extracellular exosome; membrane; clathrin-coated pit; filamentous actin; plasma membrane; nuclear membrane; cytoplasm; cell cortex; microvillus; Golgi apparatus; unconventional myosin complex; endocytic vesicle; cytoplasmic vesicle; actin filament; protein-containing complex; clathrin-coated vesicle; filopodium;
Biological process	intracellular protein transport; actin filament-based movement; regulation of secretion; hearing; positive regulation of transcription by RNA polymerase II; protein transport; endocytosis; DNA damage response, signal transduction by p53 class mediator; transport;
	Sources:Amigo / QuickGO
Orthologs
	4646
	17920
	ENSG00000196586
	ENSMUSG00000033577
	Q9UM54
	Q64331
NM_001300899; NM_004999; NM_001368136; NM_001368137; NM_001368138;
	NM_001368139; NM_001368140; NM_001368865; NM_001368866
	NM_001039546; NM_008662
NP_001287828; NP_004990; NP_001355065; NP_001355066; NP_001355067;
	NP_001355068; NP_001355069; NP_001355794; NP_001355795
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

Unconventional myosin-VI, is a protein that in humans is coded for by MYO6.^[5] Unconventional myosin-VI is a myosin molecular motor involved in intracellular vesicle and organelle transport.^[6]

Structure

Human myosin-VI contains a N-terminal myosin head domain (residues 59–759), two coiled coil motifs (residues 902–984 and 986–1009 respectively), and a C-terminal myosin VI cargo binding domain (residues 1177–1267).^[7]

Function

Unconventional myosin-VI is unique because it travels in the opposite direction of other myosins, towards the negative end of actin filaments. Myosin-VI follows the same structure as other myosin but with two unique "inserts" allowing for its diversified properties. One insert is called the "reverse gear" and is responsible for its movement towards the negative end of actin filaments. The reverse gear is located on the neck region of the myosin and acts as a reorienting device for the lever arm to move backwards after myosin movement. The second insert assists in regulating ATP enzyme activity located in the motor head domain.^[8]

There are 3 amino acid binding sites essential for myosin-VI's interactions, Arg-Arg-Leu and Trp-Trp-Tyr in the tail region and Met-Ile-Sec in the helix. The Arg-Arg-Leu amino acid segment (abbreviated RRL) takes part in ubiquitin interactions while Trp-Trp-Tyr (abbreviated WWY) assists in interactions with DAB2. Myosin-VI's Met-Ile-Sec bonding interactions are limited to the myosin-VI long isoform but interact with clathrin in endocytosis.

Myosin-VI long isoform is formed by the inclusion of exon 31, adding an addition alpha-helix, restriction RRL interactions. Myosin-VI long struggles to interact with ubiquitin chains and GIPC1 due to this structural formation, however, increases attractivity to clathrin. Myosin-VI's structural flexibility provides a great width in interaction ability with its environment and interactors.^[9]

Interactions

MYO6 has been shown to interact with GIPC1,^[10]^[11] DAB2.,^[12]^[13] ubiquitin,^[14] and clathrin.^[15] Myosin VI, being a motor protein, focuses its interactions by moving along actin filaments. This however does not limit its functions, because MYO6 is heavily involved in cytokinesis, creation of membrane compartments, and the regulation and organization of actin filaments.^[16]

Clinical significance

Mutations in the MYO6 gene are associated with hearing loss.^[17] MYO6 has also been found to be involved in many events in spermiogenesis in numerous different creatures. In common fruit flies (Drosophila), the myosin-VI ortholog controls the sterility of males by organization of actin involved in spermatid individualization. This same ortholog in roundworms (C. elegans) regulates the separation of cytosol in spermatid formation due to its influence in cytokinesis. In mice, this ortholog will control specialization and membrane compartment creation.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000196586 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033577 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "MYO6 - Unconventional myosin-VI - Homo sapiens (Human) - MYO6 gene & protein". www.uniprot.org. Retrieved 7 April 2022.
^ "Entrez Gene: MYO6 myosin VI".
^ "Protein: MYO6_HUMAN (Q9UM54)". Pfam. European Molecular Biology Laboratory.
^ Zakrzewski P, Lenartowska M, Buss F (March 2021). "Diverse functions of myosin VI in spermiogenesis". Histochemistry and Cell Biology. 155 (3): 323–340. doi:10.1007/s00418-020-01954-x. PMC 8021524. PMID 33386429.
^ Magistrati E, Polo S (April 2021). "Myomics: myosin VI structural and functional plasticity". Current Opinion in Structural Biology. 67: 33–40. doi:10.1016/j.sbi.2020.09.005. hdl:2434/801699. PMID 33053464. S2CID 222421080.
^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
^ Aschenbrenner L, Lee T, Hasson T (July 2003). "Myo6 facilitates the translocation of endocytic vesicles from cell peripheries". Molecular Biology of the Cell. 14 (7): 2728–2743. doi:10.1091/mbc.E02-11-0767. PMC 165672. PMID 12857860.
^ Morris SM, Arden SD, Roberts RC, Kendrick-Jones J, Cooper JA, Luzio JP, Buss F (May 2002). "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic. 3 (5): 331–341. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127. S2CID 25079713.
^ Inoue A, Sato O, Homma K, Ikebe M (March 2002). "DOC-2/DAB2 is the binding partner of myosin VI". Biochemical and Biophysical Research Communications. 292 (2): 300–307. doi:10.1006/bbrc.2002.6636. PMID 11906161.
^ He F, Wollscheid HP, Nowicka U, Biancospino M, Valentini E, Ehlinger A, et al. (March 2016). "Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains". Cell Reports. 14 (11): 2683–2694. doi:10.1016/j.celrep.2016.01.079. PMC 4805485. PMID 26971995.
^ Biancospino M, Buel GR, Niño CA, Maspero E, Scotto di Perrotolo R, Raimondi A, et al. (October 2019). "Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension". Nature Communications. 10 (1): 4974. Bibcode:2019NatCo..10.4974B. doi:10.1038/s41467-019-12855-6. PMC 6823378. PMID 31672988.
^ ^a ^b Sweeney HL, Houdusse A (February 2007). "What can myosin VI do in cells?". Current Opinion in Cell Biology. 19 (1): 57–66. doi:10.1016/j.ceb.2006.12.005. PMID 17175153.
^ Friedman TB, Belyantseva IA, Frolenkov GI (2020). "Myosins and Hearing". Myosins. Advances in Experimental Medicine and Biology. Vol. 1239. pp. 317–330. doi:10.1007/978-3-030-38062-5_13. ISBN 978-3-030-38061-8. PMID 32451864. S2CID 218894008.

External links

Overview of all the structural information available in the PDB for UniProt: Q9UM54 (Unconventional myosin-VI) at the PDBe-KB.

This article on a gene on human chromosome 6 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000196586 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000033577 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[uniprot-5] "MYO6 - Unconventional myosin-VI - Homo sapiens (Human) - MYO6 gene & protein". www.uniprot.org. Retrieved 7 April 2022.

[entrez-6] "Entrez Gene: MYO6 myosin VI".

[7] "Protein: MYO6_HUMAN (Q9UM54)". Pfam. European Molecular Biology Laboratory.

[8] Zakrzewski P, Lenartowska M, Buss F (March 2021). "Diverse functions of myosin VI in spermiogenesis". Histochemistry and Cell Biology. 155 (3): 323–340. doi:10.1007/s00418-020-01954-x. PMC 8021524. PMID 33386429.

[9] Magistrati E, Polo S (April 2021). "Myomics: myosin VI structural and functional plasticity". Current Opinion in Structural Biology. 67: 33–40. doi:10.1016/j.sbi.2020.09.005. hdl:2434/801699. PMID 33053464. S2CID 222421080.

[pmid17353931-10] Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

[pmid12857860-11] Aschenbrenner L, Lee T, Hasson T (July 2003). "Myo6 facilitates the translocation of endocytic vesicles from cell peripheries". Molecular Biology of the Cell. 14 (7): 2728–2743. doi:10.1091/mbc.E02-11-0767. PMC 165672. PMID 12857860.

[pmid11967127-12] Morris SM, Arden SD, Roberts RC, Kendrick-Jones J, Cooper JA, Luzio JP, Buss F (May 2002). "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic. 3 (5): 331–341. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127. S2CID 25079713.

[pmid11906161-13] Inoue A, Sato O, Homma K, Ikebe M (March 2002). "DOC-2/DAB2 is the binding partner of myosin VI". Biochemical and Biophysical Research Communications. 292 (2): 300–307. doi:10.1006/bbrc.2002.6636. PMID 11906161.

[pmid26971995-14] He F, Wollscheid HP, Nowicka U, Biancospino M, Valentini E, Ehlinger A, et al. (March 2016). "Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains". Cell Reports. 14 (11): 2683–2694. doi:10.1016/j.celrep.2016.01.079. PMC 4805485. PMID 26971995.

[pmid31672988-15] Biancospino M, Buel GR, Niño CA, Maspero E, Scotto di Perrotolo R, Raimondi A, et al. (October 2019). "Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension". Nature Communications. 10 (1): 4974. Bibcode:2019NatCo..10.4974B. doi:10.1038/s41467-019-12855-6. PMC 6823378. PMID 31672988.

[Sweeney_2007-16] Sweeney HL, Houdusse A (February 2007). "What can myosin VI do in cells?". Current Opinion in Cell Biology. 19 (1): 57–66. doi:10.1016/j.ceb.2006.12.005. PMID 17175153.

[Friedman_2020-17] Friedman TB, Belyantseva IA, Frolenkov GI (2020). "Myosins and Hearing". Myosins. Advances in Experimental Medicine and Biology. Vol. 1239. pp. 317–330. doi:10.1007/978-3-030-38062-5_13. ISBN 978-3-030-38061-8. PMID 32451864. S2CID 218894008.

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