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FLASH GENE
Symbol MYO5A contributors: mct/npt/pgu - updated : 04-12-2018
HGNC name myosin VA (heavy polypeptide 12, myoxin)
HGNC id 7602
Corresponding disease
VCIPD1 variable combined immunodeficiency and pigmentary dilution 1
Location 15q21.2      Physical location : 52.599.479 - 52.821.247
Synonym name
  • myosin, heavy polypeptide kinase
  • myosin heavy chain 12
  • dilute myosin heavy chain, non-muscle
  • myosin V
  • Synonym symbol(s) GS1, MYH12, MYO5
    DNA
    TYPE functioning gene
    STRUCTURE 221.77 kb     41 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • SNAI1 can bind to an E-box of the myosin Va promoter and induce its activity, which indicates that SNAI1 might act as a transcriptional activator
  • MAPPING cloned Y linked   status confirmed
    Map cen - [D15S982 - D15S1003 ] - D15S1049 - D15S998 - D15S1022 - qter
    Physical map
    ATP8B4 15q15.3 ATPase, Class I, type 8B, member 4 SLC27A2 15q21.2 solute carrier family 27 (fatty acid transporter), member 2 HDC 15q15-q21 histidine decarboxylase GABPB2 15q15.2 GA binding protein transcription factor, beta subunit 2, 47kDa FLJ10038 15q15.3 hypothetical protein FLJ10038 USP8 6p21.3 ubiquitin specific protease 8 TRPM7 15q21 transient receptor potential cation channel, subfamily M, member 7 SPPL2A 15q15.3 putative intramembrane cleaving protease AP4E1 15q15.2 adaptor-related protein complex 4, epsilon 1 subunit LOC388121 15 similar to TNF-induced protein CYP19A1 15q21.1 cytochrome P450, family 19, subfamily A, polypeptide 1 FLJ11181 15q15.3 hypothetical protein FLJ11181 CRG-L2 15q15.3 likely ortholog of mouse cancer related gene - liver 2 RC3 15q15.3 rabconnectin-3 SCG3 15q21 secretogranin III MGC35274 15q21.1 hypothetical protein MGC35274 TMOD2 15q21.1-q21.2 tropomodulin 2 (neuronal) TMOD3 15q21.1-q21.2 tropomodulin 3 (ubiquitous) LOC123169 15q21.1 senescence downregulated leo1-like MAPK6 15q21 mitogen-activated protein kinase 6 BCL2L10 15q21 BCL2-like 10 (apoptosis facilitator) GNB5 15q21 guanine nucleotide binding protein (G protein), beta 5 MYO5C 15q21 myosin VC MYO5A 15q21.1 myosin VA (heavy polypeptide 12, myoxin) EEF1B1 15q15.1-q15.3 eukaryotic translation elongation factor 1 beta 1 ARPP-19 15q15.3 eukaryotic translation elongation factor 1 beta 1 FLJ10980 15q21.1 hypothetical protein FLJ10980 ONECUT1 15q21.1-q21.2 one cut domain, family member 1 LOC388122 15 similar to Laminin receptor 1 LOC390585 15 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu) LOC388123 15 LOC388123 FLJ38736 15q21.1 hypothetical protein FLJ38736 UNC13C 15q21.1 unc-13 homolog C (C. elegans)
    RNA
    TRANSCRIPTS type messenger
    text
  • several isoforms resulting from alternative splicing of the tail domain in dermal fibroblasts, melanocytes and keratinocytes (PMID: 9826529)
  • alternative splicing of MYO5A influences its ability to interact with MYRIP (PMID: 22993210)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    41 - 12238 215.3 1855 most abundant in melanocytes and leukocytes 2009 19008234
    40 - 12157 212 1828 brain, pancreas, testis, and is expressed in pancreatic beta cells 2009 19008234
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemtestis  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Nervousneuron
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal motor domain containing ATP and actin-binding sites
  • a light chain binding neck containing six IQ calmodulin or calmodulin-like light chain binding domains
  • connected to the base (the converter) of a long alpha helical tail with a coiled coil segment
  • a C terminal globular domain, the globular tail domain (GTD)
  • HOMOLOGY
    interspecies homolog to murine dilute gene
    Homologene
    FAMILY
  • myosin superfamily
  • CATEGORY motor/contractile , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • centrosomes
  • motor protein associated with synaptic vesicles
  • basic FUNCTION
  • unconventional non muscle, apparently non filamentous myosin
  • major actin-based vesicle transport motor that binds to one of its cargos, the melanosome, by means of a RAB27A/MLPH receptor (
  • is required for the peripheral accumulation of melanosomes in melanocytes (O'Sullivan 2004)
  • processive motor protein, moving vesicles (melanosomes) on actin tracks through a characteristic cycle of interaction with actin, the rate limiting step of the cycle being the ADP release
  • despite its known motor activity, directly mediates stable attachment of secretory granule at the plasma membrane
  • role for both myosin Va and VAMP2 in oligodendrocyte function as it relates to myelination
  • potentially involved in a transient transport or tethering function in the perinuclear region
  • play critical roles in the proper trafficking and recycling of a large number of diverse intracellular cargoes
  • multifunctional motors recruited by a variety of Rab proteins to perform multiple tasks in a variety of distinct and overlapping recycling system
  • essential role in cancer cell migration and metastasis, suggesting a novel target for SNAI1 in its regulation of cancer progression
  • mediates correct positioning of PRKAR1A in a postsynaptic microdomain, presumably by tethering PRKAR1A to the actin cytoskeleton
  • with other myosin 5, are important modulator of synaptic plasticity
  • implication of myosin Va and RAB3D in the maturation of SGs (secretory granules) where they participate in overlapping but not identical tasks
  • transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons
  • having an important role in the transport and turnover of mRNA
  • role of MYO5A in Purkinje cells spines is not sufficient for motor coordination
  • RAB27A/MYRIP/MYO5A complex is involved in linking Weibel-Palade bodies (WPB) to the peripheral actin cytoskeleton of endothelial cells to allow full maturation and prevent premature secretion of VWF
  • plays a key role in the transport of cargo to the plasma membrane
  • has also been implicated in the assembly and maintenance of P-bodies (processing bodies), cytoplasmic foci that are involved in mRNA storage and degradation
  • has no non-redundant role in the secretion of dense and alpha-granules or other functional responses in platelets
  • MYO5A and kinesin play likely key roles in the assembly and subsequent transport of FMR1 granules along microtubules to the periphery of the cell
  • MYO5A is likely involved in mRNA trafficking both in the central and peripheral nervous systems 8)
  • MYO5A and dynamic actin oppose microtubules to drive long-range organelle transport
  • is an actin-based molecular motor responsible for transport and positioning of a wide array of intracellular cargoes
  • MYO5A and endoplasmic reticulum calcium channel complex regulates membrane export during axon guidance
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text transporting cargo (melanosomes) at lower motor densities than any other characterized myosin, downregulated during mitosis
    PATHWAY
    metabolism
    signaling
    a component
  • forming a complex with RAB27A and MLPH
  • MYO5A forms a tripartite complex with RAB27A and its effector MYRIP
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • in melanocytes, MYO5A tail interacts with its cargo-binding protein melanophilin (MLPH), which associates with melanosome via RAB27A
  • interacting with DYNLL2 (promotes the assembly of the coiled-coil domains of myosin Va)
  • MYO5A but not MAPRE1 interaction is required for transport of melanosomes to peripheral dendrites
  • can interact with RAB10, based on the presence of an alternatively spliced exon sequence
  • MYRIP mediates cellular activation of MYO5A and MYO7A via non-overlapping domains
  • MYO5A -interacting protein RILPL2 (MYO5A is crucial for proper RILPL2 function)
  • MYO5A and RAB3A are direct binding partners and interact on synaptic vesicles and the MYO5A/RAB3A complex is involved in transport of neuronal vesicles
  • direct and indirect regulatory control of TYRP1 and other pigmentation and mesenchymal genes by MYO5A
  • MLPH is the adapter protein that links RAB27A-melanosomes to MYO5A
  • MYO5A is necessary for maintaining a peripheral distribution of RAB11A- and RAB14-positive endosomes
  • MYO5A mediates RAB8A-regulated SLC2A4 vesicle exocytosis in insulin-stimulated muscle cells
  • role of MYRIP in regulating Weibel-Palade body (WPB) trafficking and exocytosis is mediated largely through its interaction with actin rather than with MYO5A
  • MLPH/globular tail domain-binding domain (GTBD) is able to bind to the GTD of MYO5A in preactivated state and allosterically inhibits the binding of globular tail domain (GTD) to the head, thus inducing the extended conformation and activating the motor function of MYO5A
  • CALM1 in complex with the first IQ motif of MYO5A functions as an intact calcium sensor
  • MYO5A interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning and MYO5A and RPGRIP1L can interact near the cilium base in ciliated RPE cells
  • MYRIP accumulates granules in the cortical F-actin network not by direct interaction with MYO5A, but by indirect interaction with a specific form of MYO7A through its previously unknown binding partner, RIMBP2 (28673385)
  • membrane tethering mediated by endosomal RAB11A is drastically and selectively stimulated by its cognate Rab effectors, MYO5A and MYO5B, in a GTP-dependent manner
  • cell & other
    REGULATION
    Other anchored to particular cell domains by RNF12 through its interaction with ACTN4
    phosphorylated by CAMK-II proteins and downregulated
    motor functions of MYO5A and MYO5B are regulated by a tail inhibition mechanism
    ASSOCIATED DISORDERS
    corresponding disease(s) VCIPD1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • absence of platelet phenotype in mice lacking the motor protein Myo5a