MYO5A

Myosin-Va (MYO5A) is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments.[5][6][7] MYO5A gene encodes for the unconventional Myosin motor Va.[8][9][10]

MYO5A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4J5L, 4LX1, 4LX2, 4LLI, 4D07
Identifiers
Aliases	MYO5A, GS1, MYH12, MYO5, MYR12, myosin VA
External IDs	OMIM: 160777 MGI: 105976 HomoloGene: 20100 GeneCards: MYO5A
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q21.2 Start 52,307,283 bp[1] End 52,529,050 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 D|9 42.26 cM Start 75,071,015 bp[2] End 75,223,688 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • calcium ion binding • nucleotide binding • calmodulin binding • microfilament motor activity • Rab GTPase binding • actin binding • cellular motor activity • ATP binding • RNA binding • disordered domain specific binding • identical protein binding • GO:0001948 protein binding • actin filament binding Cellular component • cytoplasm • recycling endosome • vesicle • cytosol • late endosome • Golgi apparatus • membrane • growth cone • ruffle • melanosome • insulin-responsive compartment • photoreceptor outer segment • peroxisome • secretory granule • microtubule plus-end • filopodium tip • neuronal cell body • early endosome • endoplasmic reticulum • actin filament • neuron projection • lysosome • actomyosin • intermediate filament • extracellular exosome • myosin complex • unconventional myosin complex • smooth endoplasmic reticulum • postsynapse • glutamatergic synapse Biological process • regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity • melanin biosynthetic process • synapse organization • insulin secretion • secretory granule localization • melanosome localization • actin filament-based movement • post-Golgi vesicle-mediated transport • odontogenesis • endoplasmic reticulum localization • melanin metabolic process • regulation of Golgi organization • long-chain fatty acid biosynthetic process • melanosome transport • cellular response to insulin stimulus • vesicle transport along actin filament • protein transport • developmental pigmentation • myelination • pigmentation • protein localization to plasma membrane • melanocyte differentiation • locomotion involved in locomotory behavior • vesicle-mediated transport • visual perception • exocytosis • chemical synaptic transmission • hair follicle maturation • transport • establishment of endoplasmic reticulum localization to postsynapse • regulation of postsynaptic cytosolic calcium ion concentration Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4644	17918
Ensembl	ENSG00000197535	ENSMUSG00000034593
UniProt	Q9Y4I1	Q99104
RefSeq (mRNA)	NM_000259 NM_001142495 NM_001382347 NM_001382348 NM_001382349	NM_010864
RefSeq (protein)	NP_000250 NP_001135967 NP_001369276 NP_001369277 NP_001369278	NP_034994
Location (UCSC)	Chr 15: 52.31 – 52.53 Mb	Chr 9: 75.07 – 75.22 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

In the presence of cargo adapters and calcium, Myosin Va is present in a elongated and active state. Myosin V has an N-terminal head domain and a C-terminal tail domain. The actin-binding head (N-Terminal) of Myosin V is an ATP-dependent motor domain that transmits changes from the active site to the light chain lever arm. The C-terminal globular domain (GB) decides the Myosin class and moderate the cargo transport. Also, the GB interacts with other cargo specific proteins. Myosin Va is highly expressed in neurons and melanocytes.[5][6]

Interactions

MYO5A has been shown to interact with DYNLL1,[11] RAB27A,[12][13] DYNLL2[11][14], RPGRIP1L[15], Rab3A[6] and miR-145. [16]

Clinical significance

• Defects in Myosin Va are associated with Griscelli syndrome type 1, also known as Elejalde syndrome a rare autosomal recesive disorder. This defect is due a mutation in which a premature stop codon in the globular tail disrupt melanosome transport producing partial albinism.[5] Griscelli syndrome type 1 can present with pigment defects and neurological disorders such as, hypotonia, motor development delay and mental impairment.[17]

• Myosin Va is highly expressed in the nervous system and it is present in almost the entire brain .MY5A perform an important role in the regulation of axonal vesicle transport on the neurofilaments.[17] The GB of MYO5A can form a complex with Rab3A. The involvement of this complex is important for the synaptic vesicles (SVs) trafficking of neurotransmitters and the dynamics of the SVs on the actin filaments. [6] The absence of MYO5A in the brain can be associated with loco motor dysfunction and neuroendocrine abnormalities. As mention MYO5A is highly expressed on the neurons. Therefore, a mutation on MYO5A can be related with abnormal neuronal development and the progression of neurodegeneration.[17]

• MYO5A and MYO5B are involved with Kv1.5 (encoded by Potassium voltage-gated channel subfamily A member 5, KCNA5) in the myocytes. Kv1.5 is associated with the regulation of the action potential in the myocytes. New strategies targeting Kv1.5 current through MYO5A and MYO5B in human atrial fibrillation (AF) are being studied.[7]

• Over expression of MYO5A, it has also been seen to be related to cancer metastasis. MYO5A can be highly expressed on metastatic colorectal cancer tissues and neck lymph node metastasis of oral squamous cell carcinoma. Also, MYO5A can be a predictor marker on neck lymph node metastasis and be helpful in patient prognosis.[16]

In non-primate mammals

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[18]
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[19]
Citrobacter infection	Normal[20]
All tests and analysis from[21][22]

Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5a^{tm1e(KOMP)Wtsi}[23][24] 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.[25][26][27]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[21][28] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.[21] Male homozygous mutants had abnormal hair cycles, coat colouration and an increased susceptibility to bacterial infection.[21]

Mutations in this gene cause a form of Griscelli syndrome in horses known as "Lavender Foal Syndrome"[29]

See also

• Myosin
• MYP5B

References

1. GRCh38: Ensembl release 89: ENSG00000197535 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034593 - 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.
5. Velvarska, Hana; Niessing, Dierk (2013-12-10). "Structural Insights into the Globular Tails of the Human Type V Myosins Myo5a, Myo5b, and Myo5c". PLOS ONE. 8 (12): e82065. Bibcode:2013PLoSO...882065V. doi:10.1371/journal.pone.0082065. ISSN 1932-6203. PMC 3858360. PMID 24339992.
6. Wöllert, Torsten; Patel, Anamika; Lee, Ying-Lung; Provance, D. William; Vought, Valarie E.; Cosgrove, Michael S.; Mercer, John A.; Langford, George M. (2011-04-22). "Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons". The Journal of Biological Chemistry. 286 (16): 14352–14361. doi:10.1074/jbc.M110.187286. ISSN 0021-9258. PMC 3077635. PMID 21349835.
7. Schumacher-Bass, Sarah M.; Vesely, Eileen D.; Zhang, Lian; Ryland, Katherine E.; McEwen, Dyke P.; Chan, Priscilla J.; Frasier, Chad R.; McIntyre, Jeremy C.; Shaw, Robin M.; Martens, Jeffrey R. (2014-03-14). "A Role for Myosin V Motor Proteins in the Selective Delivery of Kv Channel Isoforms to the Membrane Surface of Cardiac Myocytes". Circulation Research. 114 (6): 982–992. doi:10.1161/CIRCRESAHA.114.302711. ISSN 0009-7330. PMC 4213814. PMID 24508725.
8. 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.
9. 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. Bibcode:1994PNAS...91.6549B. doi:10.1073/pnas.91.14.6549. PMC 44240. PMID 8022818.
10. "Entrez Gene: MYO5A myosin VA (heavy chain 12, myoxin)".
11. 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. doi:10.1523/JNEUROSCI.20-12-04524.2000. PMC 6772433. PMID 10844022.
12. 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.
13. 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.
14. 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. Bibcode:2001Sci...293.1829P. doi:10.1126/science.1062257. PMID 11546872.
15. Assis, L. H. P. et al. The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L. Sci. Rep. 7, 43692; doi: 10.1038/srep43692 (2017)
16. Zhao, Xudong; Zhang, Wei; Ji, Wenyue (2018-06-21). "MYO5A inhibition by miR-145 acts as a predictive marker of occult neck lymph node metastasis in human laryngeal squamous cell carcinoma". OncoTargets and Therapy. 11: 3619–3635. doi:10.2147/OTT.S164597. ISSN 1178-6930. PMC 6016585. PMID 29950866.
17. "ClinicalKey". www.clinicalkey.com. Retrieved 2019-12-04.
18. "Dysmorphology data for Myo5a". Wellcome Trust Sanger Institute.
19. "Salmonella infection data for Myo5a". Wellcome Trust Sanger Institute.
20. "Citrobacter infection data for Myo5a". Wellcome Trust Sanger Institute.
21. 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.
22. Mouse Resources Portal, Wellcome Trust Sanger Institute.
23. "International Knockout Mouse Consortium".
24. "Mouse Genome Informatics".
25. 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.
26. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
27. 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.
28. 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.
29. Bierman, A.; Guthrie, A. J.; Harper, C. K. (2010). "Lavender foal syndrome in Arabian horses is caused by a single-base deletion in the MYO5A gene". Animal Genetics. 41: 199–201. doi:10.1111/j.1365-2052.2010.02086.x. ISSN 0268-9146.

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. Bibcode:1999Natur.400..590M. 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. doi:10.1523/JNEUROSCI.20-12-04524.2000. PMC 6772433. 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.

External links

• Overview of all the structural information available in the PDB for UniProt: Q9Y4I1 (Unconventional myosin-Va) at the PDBe-KB.