MYO5A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMYO5A, GS1, MYH12, MYO5, MYR12, myosin VA
External IDsOMIM: 160777 MGI: 105976 HomoloGene: 20100 GeneCards: MYO5A
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

Unconventional myosin-Va is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments.[5][6][7] In humans it is coded for by the MYO5A gene.[8][9][10]

Structure

In the presence of cargo adapters and calcium, unconventional myosin Va is present in an elongated and active state. It has an N-terminal head domain and a C-terminal tail domain. The actin-binding head (N-Terminal) 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 recessive 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]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000197535 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 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. 1 2 3 4 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. 1 2 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. ↑ "MYO5A - Unconventional myosin-Va - Homo sapiens (Human) - MYO5A gene & protein". www.uniprot.org. Retrieved 11 April 2022.
  9. ↑ 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.
  10. ↑ 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.
  11. 1 2 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. S2CID 5638023.
  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. 1 2 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. 1 2 3 "ClinicalKey". www.clinicalkey.com. Retrieved 2019-12-04.

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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