MYO5A

Myosin VA (heavy chain 12, myoxin)
PDB rendering based on 1oe9.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4D07​, 4J5L​, 4LLI​, 4LX1​, 4LX2​
Identifiers
Symbols	MYO5A ; GS1; MYH12; MYO5; MYR12
External IDs	OMIM: 160777 MGI: 105976 HomoloGene: 20100 GeneCards: MYO5A Gene
Gene ontology Molecular function • microfilament motor activity • actin binding • calcium ion binding • calmodulin binding • ATP binding • Rab GTPase binding • poly(A) RNA binding Cellular component • ruffle • photoreceptor outer segment • cytoplasm • lysosome • early endosome • late endosome • peroxisome • endoplasmic reticulum • Golgi apparatus • cytosol • intermediate filament • actin filament • membrane • myosin complex • growth cone • vesicle • filopodium tip • insulin-responsive compartment • microtubule plus-end • melanosome • actomyosin • neuron projection • neuronal cell body • recycling endosome • extracellular exosome Biological process • transport • exocytosis • post-Golgi vesicle-mediated transport • synaptic transmission • visual perception • vesicle-mediated transport • actin filament-based movement • vesicle transport along actin filament • insulin secretion • melanocyte differentiation • regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity • locomotion involved in locomotory behavior • secretory granule localization • melanosome transport • cellular response to insulin stimulus • melanin biosynthetic process • odontogenesis • myelination • long-chain fatty acid biosynthetic process • cellular protein metabolic process • synapse organization • endoplasmic reticulum localization • membrane organization • protein localization to plasma membrane • regulation of Golgi organization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4644	17918
Ensembl	ENSG00000197535	ENSMUSG00000034593
UniProt	Q9Y4I1	Q99104
RefSeq (mRNA)	NM_000259	NM_010864
RefSeq (protein)	NP_000250	NP_034994
Location (UCSC)	Chr 15: 52.31 – 52.53 Mb	Chr 9: 75.07 – 75.22 Mb
PubMed search

Myosin-Va is a protein that in humans is encoded by the MYO5A gene.^[1][2][3]

Interactions

MYO5A has been shown to interact with DYNLL1,^[4] RAB27A^[5][6] and DYNLL2.^[4][7]

Clinical significance

Defects are associated with Griscelli syndrome type 1, also known as Elejalde syndrome.

Model organisms

Myo5a knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal[8]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Abnormal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Abnormal[9]
Citrobacter infection	Normal[10]
All tests and analysis from[11][12]

Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5a^{tm1e(KOMP)Wtsi[13][14]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[15][16][17]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[11][18] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.^[11] Male homozygous mutants had abnormal hair cycles, coat colouration and an increased susceptibility to bacterial infection.^[11]

See also

• Myosin

References

1. Engle LJ, Kennett RH (Feb 1994). "Cloning, analysis, and chromosomal localization of myoxin (MYH12), the human homologue to the mouse dilute gene". Genomics 19 (3): 407–16. doi:10.1006/geno.1994.1088. PMID 8188282.
2. Bement WM, Hasson T, Wirth JA, Cheney RE, Mooseker MS (Jul 1994). "Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types". Proceedings of the National Academy of Sciences of the United States of America 91 (14): 6549–53. doi:10.1073/pnas.91.14.6549. PMC 44240. PMID 8022818.
3. "Entrez Gene: MYO5A myosin VA (heavy chain 12, myoxin)".
4. Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M (Jun 2000). "Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein". The Journal of Neuroscience 20 (12): 4524–34. PMID 10844022.
5. Wu X, Wang F, Rao K, Sellers JR, Hammer JA (May 2002). "Rab27a is an essential component of melanosome receptor for myosin Va". Molecular Biology of the Cell 13 (5): 1735–49. doi:10.1091/mbc.01-12-0595. PMC 111140. PMID 12006666.
6. Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, Izumi T (Apr 2002). "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Letters 517 (1-3): 233–8. doi:10.1016/S0014-5793(02)02634-0. PMID 12062444.
7. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC, Strasser A (Sep 2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science 293 (5536): 1829–32. doi:10.1126/science.1062257. PMID 11546872.
8. "Dysmorphology data for Myo5a". Wellcome Trust Sanger Institute.
9. "Salmonella infection data for Myo5a". Wellcome Trust Sanger Institute.
10. "Citrobacter infection data for Myo5a". Wellcome Trust Sanger Institute.
11. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
12. Mouse Resources Portal, Wellcome Trust Sanger Institute.
13. "International Knockout Mouse Consortium".
14. "Mouse Genome Informatics".
15. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
16. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
17. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
18. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Moore KJ, Testa JR, Francke U, Milatovich A, Copeland NG, Jenkins NA (1995). "Cloning and regional assignment of the human myosin heavy chain 12 (MYH12) gene to chromosome band 15q21". Cytogenetics and Cell Genetics 69 (1-2): 53–8. doi:10.1159/000133937. PMID 7835087.
• Pastural E, Barrat FJ, Dufourcq-Lagelouse R, Certain S, Sanal O, Jabado N, Seger R, Griscelli C, Fischer A, de Saint Basile G (Jul 1997). "Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene". Nature Genetics 16 (3): 289–92. doi:10.1038/ng0797-289. PMID 9207796.
• Lambert J, Naeyaert JM, Callens T, De Paepe A, Messiaen L (Nov 1998). "Human myosin V gene produces different transcripts in a cell type-specific manner". Biochemical and Biophysical Research Communications 252 (2): 329–33. doi:10.1006/bbrc.1998.9644. PMID 9826529.
• Buss F, Kendrick-Jones J, Lionne C, Knight AE, Côté GP, Paul Luzio J (Dec 1998). "The localization of myosin VI at the golgi complex and leading edge of fibroblasts and its phosphorylation and recruitment into membrane ruffles of A431 cells after growth factor stimulation". The Journal of Cell Biology 143 (6): 1535–45. doi:10.1083/jcb.143.6.1535. PMC 2132970. PMID 9852149.
• El-Husseini AE, Vincent SR (Jul 1999). "Cloning and characterization of a novel RING finger protein that interacts with class V myosins". The Journal of Biological Chemistry 274 (28): 19771–7. doi:10.1074/jbc.274.28.19771. PMID 10391919.
• Mehta AD, Rock RS, Rief M, Spudich JA, Mooseker MS, Cheney RE (Aug 1999). "Myosin-V is a processive actin-based motor". Nature 400 (6744): 590–3. doi:10.1038/23072. PMID 10448864.
• Edgar AJ, Bennett JP (Aug 1999). "Inhibition of dendrite formation in mouse melanocytes transiently transfected with antisense DNA to myosin Va". Journal of Anatomy 195 (2): 173–84. doi:10.1046/j.1469-7580.1999.19520173.x. PMC 1467982. PMID 10529054.
• Pastural E, Ersoy F, Yalman N, Wulffraat N, Grillo E, Ozkinay F, Tezcan I, Gediköglu G, Philippe N, Fischer A, de Saint Basile G (Feb 2000). "Two genes are responsible for Griscelli syndrome at the same 15q21 locus". Genomics 63 (3): 299–306. doi:10.1006/geno.1999.6081. PMID 10704277.
• Lambert J, Naeyaert JM, De Paepe A, Van Coster R, Ferster A, Song M, Messiaen L (Apr 2000). "arg-cys substitution at codon 1246 of the human myosin Va gene is not associated with Griscelli syndrome". The Journal of Investigative Dermatology 114 (4): 731–3. doi:10.1046/j.1523-1747.2000.00933.x. PMID 10733681.
• Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M (Jun 2000). "Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein". The Journal of Neuroscience 20 (12): 4524–34. PMID 10844022.
• Lo KW, Naisbitt S, Fan JS, Sheng M, Zhang M (Apr 2001). "The 8-kDa dynein light chain binds to its targets via a conserved (K/R)XTQT motif". The Journal of Biological Chemistry 276 (17): 14059–66. doi:10.1074/jbc.M010320200. PMID 11148209.
• Ohkawa N, Kokura K, Matsu-Ura T, Obinata T, Konishi Y, Tamura TA (Jul 2001). "Molecular cloning and characterization of neural activity-related RING finger protein (NARF): a new member of the RBCC family is a candidate for the partner of myosin V". Journal of Neurochemistry 78 (1): 75–87. doi:10.1046/j.1471-4159.2001.00373.x. PMID 11432975.
• Fukuda M, Kuroda TS, Mikoshiba K (Apr 2002). "Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport". The Journal of Biological Chemistry 277 (14): 12432–6. doi:10.1074/jbc.C200005200. PMID 11856727.
• Rodriguez OC, Cheney RE (Mar 2002). "Human myosin-Vc is a novel class V myosin expressed in epithelial cells". Journal of Cell Science 115 (Pt 5): 991–1004. PMID 11870218.
• Strom M, Hume AN, Tarafder AK, Barkagianni E, Seabra MC (Jul 2002). "A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport". The Journal of Biological Chemistry 277 (28): 25423–30. doi:10.1074/jbc.M202574200. PMID 11980908.
• Wu X, Wang F, Rao K, Sellers JR, Hammer JA (May 2002). "Rab27a is an essential component of melanosome receptor for myosin Va". Molecular Biology of the Cell 13 (5): 1735–49. doi:10.1091/mbc.01-12-0595. PMC 111140. PMID 12006666.
• Anikster Y, Huizing M, Anderson PD, Fitzpatrick DL, Klar A, Gross-Kieselstein E, Berkun Y, Shazberg G, Gahl WA, Hurvitz H (Aug 2002). "Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A". American Journal of Human Genetics 71 (2): 407–14. doi:10.1086/341606. PMC 379173. PMID 12058346.
• Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, Izumi T (Apr 2002). "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Letters 517 (1-3): 233–8. doi:10.1016/S0014-5793(02)02634-0. PMID 12062444.