MYO5A

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 52,307,281 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 Top expressed in dorsolateral prefrontal cortex neocortex Brodmann area 46 corpus callosum brain subthalamic nucleus caudate nucleus parietal lobe 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 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: 74.98 – 75.13 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/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 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]

In non-primate mammals[]

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[]

Further reading[]

External links[]

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