MYO5A encodes unconventional myosin-Va, a class V myosin heavy chain that dimerizes into a two-headed, processive actin-based motor. Each heavy chain has an N-terminal ATPase motor domain, a neck with six IQ motifs that bind calmodulin and light chains, a coiled-coil dimerization region and a C-terminal globular tail that binds cargo. Myosin-Va walks along actin filaments in large steps and transports and tethers membrane organelles in the actin-rich cell cortex. Its cargo adaptors include RAB27A-melanophilin for melanosome capture and transport in melanocytes, and direct interactions with several Rab GTPases (RAB3, RAB8, RAB10, RAB11 and others) for recycling-endosome, secretory and post-Golgi carriers in many cell types, including neurons, where it moves vesicles and smooth ER in dendrites and growth cones. At the onset of primary cilium formation, myosin-Va carries preciliary vesicles along a branched actin network from the pericentrosomal region to the distal appendages of the mother centriole, upstream of EHD1- and RAB11-dependent ciliary vesicle formation. Biallelic loss-of-function variants cause Griscelli syndrome type 1 (pigmentary dilution with neurological impairment).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000146 microfilament motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Microfilament motor activity (IBA). Reason: Myosin-Va is a processive, ATP-driven actin-based motor; this is its core molecular activity. Supporting Evidence: PMID:10448864 Here we provide direct evidence that myosin-V is indeed a processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. |
| GO:0000146 microfilament motor activity | NAS PMID:10448864 Myosin-V is a processive actin-based motor. | ACCEPT | Summary: Microfilament motor activity (NAS). Reason: Myosin-Va is a processive, ATP-driven actin-based motor; this is its core molecular activity. Supporting Evidence: PMID:10448864 Here we provide direct evidence that myosin-V is indeed a processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. |
| GO:0001726 ruffle | IDA PMID:9852149 The localization of myosin VI at the golgi complex and leadi... | KEEP AS NON CORE | Summary: Ruffle (IDA). Reason: Myosin V was recruited into EGF-stimulated membrane ruffles in A431 cells (a study focused on myosin VI); peripheral observation. Supporting Evidence: PMID:9852149 In A431 cells in which cell surface ruffling was stimulated by EGF, myosin VI was phosphorylated and recruited into the newly formed ruffles along with ezrin and myosin V. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: RNA binding (HDA) from an mRNA interactome capture screen. Reason: High-throughput poly(A)-RNA interactome capture identifies many abundant cytoskeletal proteins; there is no targeted evidence that myosin-Va has a direct RNA-binding activity as part of its function. |
| GO:0003774 cytoskeletal motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoskeletal motor activity (IEA, InterPro). Reason: Correct parent of the more specific microfilament motor activity, which is also annotated. |
| GO:0003824 catalytic activity | IEA GO_REF:0000117 | MODIFY | Summary: Catalytic activity (IEA, ARBA). Reason: Uninformative root-level term; the catalytic activity of the myosin motor domain is ATP hydrolysis coupled to movement on actin. Proposed replacements: ATP hydrolysis activity |
| GO:0005515 protein binding | IPI PMID:11980908 A family of Rab27-binding proteins. Melanophilin links Rab27... | REMOVE | Summary: Generic protein binding (IPI) for MYO5A. Partner in this record is melanophilin, the RAB27A-myosin-Va linker on melanosomes. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (IEA). Reason: The myosin motor domain binds ATP; required for motor activity. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm (IBA). Reason: Myosin-Va is a cytoplasmic motor. |
| GO:0005737 cytoplasm | IDA PMID:9852149 The localization of myosin VI at the golgi complex and leadi... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Myosin-Va is a cytoplasmic motor. |
| GO:0005764 lysosome | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | MARK AS OVER ANNOTATED | Summary: Colocalizes with lysosome (IDA). Reason: The cited study reports only limited overlap of myosin-Va with late endosome/lysosome and peroxisome markers, and myosin-Va depletion did not affect late endosome/lysosome distribution; this colocalization is not a meaningful site of function. Supporting Evidence: PMID:24006491 Limited overlap was observed with markers of late endosomes/lysosomes (LAMP1) and peroxisomes (PMP70 |
| GO:0005769 early endosome | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | KEEP AS NON CORE | Summary: Colocalizes with early endosome (IDA). Reason: Myosin-Va depletion causes perinuclear accumulation of EEA1 early endosomes; association is secondary to its recycling-pathway role. Supporting Evidence: PMID:24006491 Myosin Va depletion also caused a similar accumulation of EEA1-labeled early endosomes in the perinuclear region |
| GO:0005770 late endosome | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | MARK AS OVER ANNOTATED | Summary: Colocalizes with late endosome (IDA). Reason: The cited study reports only limited overlap of myosin-Va with late endosome/lysosome and peroxisome markers, and myosin-Va depletion did not affect late endosome/lysosome distribution; this colocalization is not a meaningful site of function. Supporting Evidence: PMID:24006491 Limited overlap was observed with markers of late endosomes/lysosomes (LAMP1) and peroxisomes (PMP70 |
| GO:0005777 peroxisome | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | MARK AS OVER ANNOTATED | Summary: Colocalizes with peroxisome (IDA). Reason: The cited study reports only limited overlap of myosin-Va with late endosome/lysosome and peroxisome markers, and myosin-Va depletion did not affect late endosome/lysosome distribution; this colocalization is not a meaningful site of function. Supporting Evidence: PMID:24006491 Limited overlap was observed with markers of late endosomes/lysosomes (LAMP1) and peroxisomes (PMP70 |
| GO:0005783 endoplasmic reticulum | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | KEEP AS NON CORE | Summary: Colocalizes with endoplasmic reticulum (IDA). Reason: Considerable colocalization with an ER marker was observed; consistent with known myosin-Va roles in smooth ER transport in neurons, but not core in non-neuronal cells. Supporting Evidence: PMID:24006491 both myosin Va isoforms displayed considerable colocalization with the endoplasmic reticulum (ER) marker protein Grp78 |
| GO:0005829 cytosol | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Cytosol (IDA). Reason: Exogenous full-length myosin-Va is predominantly cytosolic, with a membrane-bound fraction. Supporting Evidence: PMID:24006491 Exogenous full-length myosin Va is predominantly cytosolic, with a fraction localizing to the tips of filopodia |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9856462 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Consistent with direct observation that exogenous myosin-Va is predominantly cytosolic, with a membrane-bound fraction recruited by Rab GTPases. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9856465 | ACCEPT | Summary: Cytosol (TAS, Reactome). Reason: Consistent with direct observation that exogenous myosin-Va is predominantly cytosolic, with a membrane-bound fraction recruited by Rab GTPases. |
| GO:0005884 actin filament | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Colocalizes with actin filament (IDA). Reason: Myosin-Va moves on actin filaments. |
| GO:0006892 post-Golgi vesicle-mediated transport | IMP PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Post-Golgi vesicle-mediated transport (IMP). Reason: Myosin-Va binds Rab6 and associates with Rab6-positive post-Golgi carriers; depletion results in persistent Rab6-positive tubules emanating from the Golgi. Supporting Evidence: PMID:24006491 in myosin Va–depleted cells, short, Rab6A′-positive tubules emanating from the Golgi complex could be readily observed |
| GO:0006897 endocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Endocytosis (IBA, PANTHER:PTN008546178). Reason: The PAINT node places endocytosis at a myosin ancestor with experimentally characterized descendants. MYO5A-specific evidence concerns recycling-endosome, secretory and organelle transport rather than the internalization step; endocytic membrane trafficking in the broad sense is consistent with this, so the inherited annotation is retained as non-core rather than challenged. |
| GO:0007015 actin filament organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Actin filament organization (IBA, PANTHER:PTN000320364). Reason: Deep myosin-family inference from many experimentally studied myosins. For myosin-Va the documented role is cargo transport using actin as a track; direct MYO5A evidence for organizing actin filaments is lacking, so the inherited annotation is kept as non-core. |
| GO:0015629 actin cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: Actin cytoskeleton (IBA). Reason: Myosin-Va acts on the actin cytoskeleton. |
| GO:0015629 actin cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: Actin cytoskeleton (IEA). Reason: Myosin-Va acts on the actin cytoskeleton. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: Membrane (HDA). Reason: Myosin-Va is recruited to organelle and vesicle membranes via Rab GTPases and adaptors. Supporting Evidence: PMID:24006491 Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane (IBA). Reason: Myosin-Va is recruited to organelle and vesicle membranes via Rab GTPases and adaptors. Supporting Evidence: PMID:24006491 Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes |
| GO:0016020 membrane | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Membrane (IDA). Reason: Myosin-Va is recruited to organelle and vesicle membranes via Rab GTPases and adaptors. Supporting Evidence: PMID:24006491 Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes |
| GO:0016192 vesicle-mediated transport | ISS GO_REF:0000024 | ACCEPT | Summary: Vesicle-mediated transport (ISS). Reason: General but correct; myosin-Va transports multiple vesicle classes. Supporting Evidence: PMID:24006491 Myosin Va has been well characterized in melanocytes and neuronal cells, where it plays a key role in melanosome and secretory vesicle transport, respectively |
| GO:0016459 myosin complex | IEA GO_REF:0000002 | ACCEPT | Summary: Myosin complex (IEA). Reason: Myosin-Va heavy chains form a dimeric complex with calmodulin/light chains bound at the IQ motifs. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:10448864 Myosin-V is a processive actin-based motor. | ACCEPT | Summary: ATP hydrolysis activity (IDA). Reason: The myosin motor domain is an actin-activated ATPase; ATP hydrolysis drives processive stepping. Supporting Evidence: PMID:10448864 Processivity means that the motor undergoes multiple catalytic cycles and coupled mechanical advances for each diffusional encounter with its track. |
| GO:0030048 actin filament-based movement | IEA GO_REF:0000117 | ACCEPT | Summary: Actin filament-based movement (IEA). Reason: Direct consequence of the processive motor activity. Supporting Evidence: PMID:10448864 Here we provide direct evidence that myosin-V is indeed a processive actin-based motor |
| GO:0030048 actin filament-based movement | NAS PMID:10448864 Myosin-V is a processive actin-based motor. | ACCEPT | Summary: Actin filament-based movement (NAS). Reason: Direct consequence of the processive motor activity. Supporting Evidence: PMID:10448864 Here we provide direct evidence that myosin-V is indeed a processive actin-based motor |
| GO:0030050 vesicle transport along actin filament | IMP PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Vesicle transport along actin filament (IMP). Reason: Core process: myosin-Va transports Rab-marked vesicles (recycling endosome and post-Golgi carriers); its depletion causes perinuclear clustering of recycling-pathway membranes. Supporting Evidence: PMID:24006491 RNAi-mediated knockdown of myosin Va resulted in the accumulation of TfR-positive membranes in the perinuclear region of the cell |
| GO:0030426 growth cone | NAS PMID:10391919 Cloning and characterization of a novel RING finger protein ... | KEEP AS NON CORE | Summary: growth cone (NAS). Reason: Myosin-Va is abundant in neurons and present in neurites and growth cones, where it transports vesicles; a tissue-specific location relevant to its neurological phenotype. Supporting Evidence: PMID:10391919 Like myosin Va, BERP is expressed in a punctate pattern in the cytoplasm as well as in the neurites and growth cones of PC12 cells. |
| GO:0031267 small GTPase binding | IEA GO_REF:0000117 | ACCEPT | Summary: Small GTPase binding (IEA). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:15357836 Rab27b is up-regulated in human Griscelli syndrome type II m... | MARK AS OVER ANNOTATED | Summary: Small GTPase binding (IPI) with RAB27B, from a study of a Griscelli syndrome type II patient. Reason: The study describes a tripartite complex in which RAB27B binds myosin-Va (exon F isoform) via melanophilin; the RAB27-myosin-Va association is indirect, so a direct small GTPase binding assertion over-states the evidence. Supporting Evidence: PMID:15357836 Rab27b can form a tripartite complex on the melanosome membrane with Melanophilin, a Rab27a effector, and protein products of Myosin Va transcripts that contain exon F |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031267 small GTPase binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Small GTPase binding (IPI). Reason: Myosin-Va directly binds multiple Rab GTPases through three distinct tail regions (Rab6/Rab14, Rab8/Rab10 on exon D, Rab3/Rab11/Rab39B in the globular tail); Rab binding links the motor to its vesicle cargo. Rab GTPase binding (GO:0017137) would be a more specific child term. Supporting Evidence: PMID:24006491 we report a yeast two-hybrid screen of all human Rabs for myosin Va-binding ability and reveal 10 novel interactions PMID:24006491 Although the total pool of myosin Va is shared by several Rabs, Rab10 and Rab11 appear to be the major determinants of its recruitment to intracellular membranes. |
| GO:0031982 vesicle | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Colocalizes with vesicle (IDA). Reason: Myosin-Va colocalizes with Rab11/Rab10-positive recycling-endosome vesicles that it transports. Supporting Evidence: PMID:24006491 Myosin Va depletion induces perinuclear clustering of endocytic recycling pathway membrane compartments. |
| GO:0032402 melanosome transport | NAS PMID:11980908 A family of Rab27-binding proteins. Melanophilin links Rab27... | ACCEPT | Summary: Melanosome transport (NAS). Reason: Classic myosin-Va function: recruited to melanosomes via RAB27A-melanophilin and required for peripheral melanosome capture; loss causes Griscelli syndrome type 1 pigment dilution. Supporting Evidence: PMID:11980908 Melanophilin links Rab27a and myosin Va function in melanosome transport. file:human/MYO5A/MYO5A-deep-research-falcon.md The motor moves and helps retain pigment-bearing melanosomes within the peripheral actin network and melanocyte dendrites, positioning them for transfer to neighboring keratinocytes. |
| GO:0032433 filopodium tip | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | KEEP AS NON CORE | Summary: Filopodium tip (IDA). Reason: Observed for overexpressed myosin-Va; consistent with processive movement to actin barbed ends but not a core site of function. Supporting Evidence: PMID:24006491 Exogenous full-length myosin Va is predominantly cytosolic, with a fraction localizing to the tips of filopodia |
| GO:0032593 insulin-responsive compartment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: insulin-responsive compartment (ISS), transferred from rodent adipocyte studies of insulin-stimulated GLUT4 vesicle translocation. Reason: Myosin-Va has been implicated in insulin-stimulated GLUT4 vesicle delivery to the plasma membrane in adipocytes; plausible cell-type-specific vesicle transport role, retained as non-core. |
| GO:0032869 cellular response to insulin stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to insulin stimulus (ISS), transferred from rodent adipocyte studies of insulin-stimulated GLUT4 vesicle translocation. Reason: Myosin-Va has been implicated in insulin-stimulated GLUT4 vesicle delivery to the plasma membrane in adipocytes; plausible cell-type-specific vesicle transport role, retained as non-core. |
| GO:0042470 melanosome | IDA PMID:11980908 A family of Rab27-binding proteins. Melanophilin links Rab27... | ACCEPT | Summary: Melanosome localization (IDA). Reason: Myosin-Va associates with melanosomes through RAB27A-melanophilin. Supporting Evidence: PMID:11980908 We also show that melanophilin associates with Rab27a and myosin Va on melanosomes in melanocytes |
| GO:0043005 neuron projection | NAS PMID:10391919 Cloning and characterization of a novel RING finger protein ... | KEEP AS NON CORE | Summary: neuron projection (NAS). Reason: Myosin-Va is abundant in neurons and present in neurites and growth cones, where it transports vesicles; a tissue-specific location relevant to its neurological phenotype. Supporting Evidence: PMID:10391919 Like myosin Va, BERP is expressed in a punctate pattern in the cytoplasm as well as in the neurites and growth cones of PC12 cells. |
| GO:0051650 establishment of vesicle localization | IEA GO_REF:0000117 | ACCEPT | Summary: Establishment of vesicle localization (IEA, ARBA). Reason: Myosin-Va transports and tethers vesicles and organelles in the cell cortex. |
| GO:0055037 recycling endosome | IDA PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Colocalizes with recycling endosome (IDA). Reason: Myosin-Va colocalizes with Rab11/Rab10-positive recycling-endosome vesicles that it transports. Supporting Evidence: PMID:24006491 Myosin Va depletion induces perinuclear clustering of endocytic recycling pathway membrane compartments. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome (HDA). Reason: Detection in exosome proteomics reflects incidental inclusion of an abundant cytoplasmic protein; there is no evidence that myosin-Va functions in exosomes. |
| GO:0072659 protein localization to plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: protein localization to plasma membrane (ISS), transferred from rodent adipocyte studies of insulin-stimulated GLUT4 vesicle translocation. Reason: Myosin-Va has been implicated in insulin-stimulated GLUT4 vesicle delivery to the plasma membrane in adipocytes; plausible cell-type-specific vesicle transport role, retained as non-core. |
| GO:1903358 regulation of Golgi organization | IMP NOT PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: NOT regulation of Golgi organization (IMP). Reason: Myosin-Va knockdown did not alter Golgi distribution or morphology, supporting the negative annotation. Supporting Evidence: PMID:24006491 Myosin Va knockdown had no obvious effect on Golgi distribution or morphology |
| GO:0060271 cilium assembly | IMP PMID:29335527 Myosin-Va is required for preciliary vesicle transportation ... | NEW | Summary: Proposed: myosin-Va transports preciliary vesicles to the mother centriole distal appendages at the onset of primary cilium assembly. Reason: Myosin-Va does part of the work of ciliogenesis: it is the motor that carries preciliary vesicles along branched actin to the distal appendages, and its depletion blocks vesicle attachment and reduces cilia assembly. EHD1 and EHD3, which act at the next step, already carry this term. The broader cilium assembly term is preferred to ciliary vesicle assembly because myosin-Va acts upstream of ciliary vesicle formation (delivery, not fusion/tubulation). Supporting Evidence: PMID:29335527 Here, we demonstrate that myosin-Va mediates the transportation of preciliary vesicles to the mother centriole and reveal the underlying mechanism. PMID:29335527 Depletion of myosin-Va significantly inhibits the attachment of preciliary vesicles to the distal appendages of the mother centriole and decreases cilia assembly. PMID:29335527 Myosin-Va functions upstream of EHD1- and Rab11-mediated ciliary vesicle formation. |
Loading supporting content…
Download this section (compressed HTML)Q: Which cargo adaptor (e.g. a Rab such as RAB11/RAB10, or another tail-binding partner) links myosin-Va to preciliary vesicles, and is the ciliary role shared with myosin-Vb?
Q: Do Griscelli syndrome type 1 patients or dilute mice show ciliary phenotypes, given the in vitro requirement of myosin-Va for preciliary vesicle delivery?
Experiment: Rescue MYO5A-knockout RPE1 cells with motor-dead and cargo-binding-domain mutants and quantify distal-appendage vesicle docking (EM/expansion microscopy) and ciliation.
Experiment: Assess primary cilia frequency and length in fibroblasts from Griscelli syndrome type 1 patients.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)