Unconventional myosin-Va

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; OMA:MYO5A - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q21.2 Start 52,307,281 bp [1] End 52,529,132 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9 D|9 42.26 cM Start 74,978,297 bp [2] End 75,130,970 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus endothelial cell pars compacta Brodmann area 23 pars reticulata parietal lobe postcentral gyrus pons superior frontal gyrus entorhinal cortex Top expressed in medial geniculate nucleus pontine nuclei medial dorsal nucleus ventral tegmental area lateral geniculate nucleus stroma of bone marrow subiculum dorsal tegmental nucleus habenula globus pallidus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding nucleotide binding calmodulin binding microfilament motor activity actin binding cytoskeletal motor activity ATP binding RNA binding disordered domain specific binding identical protein binding 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 soma 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: 74.98 – 75.13 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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] and Rab3A. ^[6]

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. ^[16]
• 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. ^[16] 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. ^[16]
• 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]

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 H, Niessing D (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 T, Patel A, Lee YL, Provance DW, Vought VE, Cosgrove MS, et al. (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 SM, Vesely ED, Zhang L, Ryland KE, McEwen DP, Chan PJ, et al. (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): 407–416. 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): 6549–6553. Bibcode:1994PNAS...91.6549B. doi: 10.1073/pnas.91.14.6549 . PMC   44240 . PMID   8022818.
11. Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, et al. (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): 4524–4534. 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): 1735–1749. doi:10.1091/mbc.01-12-0595. PMC   111140 . PMID   12006666.
13. Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, et al. (Apr 2002). "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Letters. 517 (1–3): 233–238. Bibcode:2002FEBSL.517..233N. doi: 10.1016/S0014-5793(02)02634-0 . PMID   12062444.
14. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, et al. (Sep 2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science. 293 (5536). New York, N.Y.: 1829–1832. Bibcode:2001Sci...293.1829P. doi:10.1126/science.1062257. PMID   11546872. S2CID   5638023.
15. Assis LH, Silva-Junior RM, Dolce LG, Alborghetti MR, Honorato RV, Nascimento AF, et al. (2017). "The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L". Scientific Reports. 7 43692. Bibcode:2017NatSR...743692A. doi:10.1038/srep43692. PMC   5339802 . PMID   28266547.
16. "ClinicalKey". www.clinicalkey.com. Retrieved 2019-12-04.

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): 53–58. doi:10.1159/000133937. PMID   7835087.
• Pastural E, Barrat FJ, Dufourcq-Lagelouse R, Certain S, Sanal O, Jabado N, et al. (Jul 1997). "Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene". Nature Genetics. 16 (3): 289–292. doi:10.1038/ng0797-289. PMID   9207796. S2CID   21815627.
• 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): 329–333. Bibcode:1998BBRC..252..329L. 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): 1535–1545. 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): 19771–19777. 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): 590–593. Bibcode:1999Natur.400..590M. doi:10.1038/23072. PMID   10448864. S2CID   204995058.
• 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 (Pt 2): 173–184. 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, et al. (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, et al. (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): 731–733. doi: 10.1046/j.1523-1747.2000.00933.x . PMID   10733681.
• Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, et al. (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): 4524–4534. 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): 14059–14066. 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): 12432–12436. 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. doi:10.1242/jcs.115.5.991. 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): 25423–25430. 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): 1735–1749. doi:10.1091/mbc.01-12-0595. PMC   111140 . PMID   12006666.
• Anikster Y, Huizing M, Anderson PD, Fitzpatrick DL, Klar A, Gross-Kieselstein E, et al. (Aug 2002). "Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A". American Journal of Human Genetics. 71 (2): 407–414. doi:10.1086/341606. PMC   379173 . PMID   12058346.
• Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, et al. (Apr 2002). "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Letters. 517 (1–3): 233–238. Bibcode:2002FEBSL.517..233N. 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 .