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Unconventional myosin-Va

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MYO5A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMYO5A, GS1, MYH12, MYO5, MYR12, myosin VA
External IDsOMIM: 160777; MGI: 105976; HomoloGene: 20100; GeneCards: MYO5A; OMA:MYO5A - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 9: 74.98 – 75.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure

In the presence of cargo adapters and calcium, Myosin Va is present in an 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

Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5atm1e(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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197535 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b c 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ a b c d 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ a b 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. ^ a b 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. ^ a b 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ a b c "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. ^ a b c d 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  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

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