MYH10 encodes non-muscle myosin heavy chain IIB (NMHC II-B), the heavy chain of non-muscle myosin IIB, a conventional class II myosin. Two heavy chains dimerize through their coiled-coil rod and associate with essential and regulatory light chains; regulatory light chain phosphorylation (e.g. by MLCK or ROCK) unfolds the compact molecule into bipolar filaments. The N-terminal motor domain is an actin-activated MgATPase with high duty ratio and strong ADP affinity, suited to tension maintenance. NM IIB cross-links and contracts actin filaments in stress fibers, the cell cortex and the cleavage furrow, contributing to cytokinesis, cell shape, cell spreading and lamellipodial dynamics, and in secretory cells to regulated exocytosis. It is the predominant myosin II in the nervous system (with neuron-specific spliced isoforms) and is required for migration of several neuronal populations, where actomyosin contraction assists forward nuclear translocation, as well as for growth-cone and dendritic-spine actin dynamics; it is also essential for heart and brain development in mice. NM IIB also tethers LARP6-bound collagen mRNAs to coordinate type I collagen synthesis and can serve as an HSV-1 entry co-receptor. MYH10 variants are associated with intellectual disability, microcephaly and cerebral atrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000146 microfilament motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Microfilament motor activity inferred for the conventional myosin II family. Reason: Core molecular function. MYH10 is the heavy chain of non-muscle myosin IIB, a class II actin-activated MgATPase that assembles into bipolar filaments and translocates actin filaments, generating contractile force. Supporting Evidence: PMID:15845534 we characterized the in vitro activity of mutated and wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C PMID:24072716 RLC phosphorylated NM IIB filaments are capable of binding to and translocating along actin filaments as a processive unit |
| GO:0000146 microfilament motor activity | IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ... | ACCEPT | Summary: Actin-activated MgATPase and in vitro motility of recombinant human NM IIB heavy meromyosin. Reason: Core molecular function. MYH10 is the heavy chain of non-muscle myosin IIB, a class II actin-activated MgATPase that assembles into bipolar filaments and translocates actin filaments, generating contractile force. Supporting Evidence: PMID:15845534 we characterized the in vitro activity of mutated and wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C PMID:15845534 Comparison of the actin-activated MgATPase activity and in vitro motility shows that mutation of residues Asn-97 and Arg-709 in HMM II-B |
| GO:0000146 microfilament motor activity | IMP PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: Full-length human NM IIB with light chains forms filaments that bind and translocate along actin (contributes_to, as a subunit of the hexameric motor). Reason: Core molecular function. MYH10 is the heavy chain of non-muscle myosin IIB, a class II actin-activated MgATPase that assembles into bipolar filaments and translocates actin filaments, generating contractile force. The contributes_to qualifier appropriately reflects that motor activity is exerted by the hexamer with light chains. Supporting Evidence: PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP. PMID:24072716 RLC phosphorylated NM IIB filaments are capable of binding to and translocating along actin filaments as a processive unit |
| GO:0000281 mitotic cytokinesis | IBA GO_REF:0000033 | ACCEPT | Summary: Mitotic cytokinesis, phylogenetically inferred for myosin II. Reason: Non-muscle myosin II concentrates in the cleavage furrow and drives contractile-ring constriction; NM IIB knockdown causes cytokinesis failure (multinucleation) rescued by exogenous NM II. Supporting Evidence: PMID:15774463 62.4 +/- 8.8% of the NMHC II-B RNAi-treated cells were multinucleated 72 h after transfection PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate. |
| GO:0000281 mitotic cytokinesis | IDA PMID:15774463 Vertebrate nonmuscle myosin II isoforms rescue small interfe... | ACCEPT | Summary: NM IIB knockdown in COS-7 cells causes multinucleation, rescued by GFP-NMHC II-B. Reason: Non-muscle myosin II concentrates in the cleavage furrow and drives contractile-ring constriction; NM IIB knockdown causes cytokinesis failure (multinucleation) rescued by exogenous NM II. Supporting Evidence: PMID:15774463 62.4 +/- 8.8% of the NMHC II-B RNAi-treated cells were multinucleated 72 h after transfection |
| GO:0001618 virus receptor activity | IDA PMID:25428876 Nonmuscle myosin heavy chain IIb mediates herpes simplex vir... | KEEP AS NON CORE | Summary: NM IIB acts as an HSV-1 glycoprotein B-associated entry co-receptor. Reason: Knockdown/overexpression and co-precipitation show NM IIB associates with HSV-1 gB at the cell surface and mediates entry. This is a pathogen exploitation of a host cytoskeletal motor, not a normal physiological function. Supporting Evidence: PMID:25428876 NMHC-IIB coprecipitated with gB in COS-1 cells upon HSV-1 entry PMID:25428876 NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry |
| GO:0001725 stress fiber | IDA PMID:15774463 Vertebrate nonmuscle myosin II isoforms rescue small interfe... | ACCEPT | Summary: NM IIB-depleted cells lack stress fibers. Reason: NM IIB is a stress-fiber component (see also PMID:7699007); knockdown abolished stress fibers. Supporting Evidence: PMID:15774463 The RNAi-treated cells had increased surface areas and, unlike control cells, lacked actin stress fibers. PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. |
| GO:0001725 stress fiber | IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul... | ACCEPT | Summary: Myosin-IIB localizes in spots along stress fibers, especially perinuclear ones. Reason: Direct immunolocalization. Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. |
| GO:0001725 stress fiber | IEA GO_REF:0000107 | ACCEPT | Summary: Stress fiber, transferred from orthologs. Reason: Consistent with human experimental localization. Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. |
| GO:0003774 cytoskeletal motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoskeletal motor activity from InterPro myosin head domain. Reason: Correct parent of microfilament motor activity; the myosin motor domain is intact and catalytically active. Supporting Evidence: PMID:15845534 we characterized the in vitro activity of mutated and wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C |
| GO:0003779 actin binding | NAS PMID:7782316 Neuronal cell expression of inserted isoforms of vertebrate ... | ACCEPT | Summary: Actin binding, author statement in a paper on neuronal NMHC II-B splice isoforms. Reason: Actin binding by the myosin II motor domain is well established; the more precise term actin filament binding is also annotated with direct evidence. Supporting Evidence: PMID:7782316 they contain inserted cassettes of amino acids near the ATP binding region and/or near the actin binding region PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0005515 protein binding | IPI PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | REMOVE | Summary: Co-immunoprecipitation of myosin IIB with LARP6. Reason: GO:0005515 is uninformative. LARP6 binds NM II through its C-terminal domain to tether collagen mRNAs to myosin filaments; the interaction is real, but NM IIB performs no defined molecular function toward LARP6 that would warrant a specific MF term. Supporting Evidence: PMID:20603131 LARP6 interacts with nonmuscle myosin through its C-terminal domain and associates collagen mRNAs with the filaments. |
| GO:0005515 protein binding | IPI PMID:7542763 A human homologue of the Drosophila tumour suppressor gene l... | REMOVE | Summary: Association of the tumour suppressor homolog HUGL (LLGL1) with nonmuscle myosin II heavy chain. Reason: GO:0005515 is uninformative; the abstract reports co-association in a cytoskeletal network without defining a myosin activity toward LLGL1. Supporting Evidence: PMID:7542763 HUGL is part of a cytoskeletal network and, is associated with nonmuscle myosin II heavy chain |
| GO:0005524 ATP binding | IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ... | ACCEPT | Summary: ATP binding shown through actin-activated MgATPase kinetics of NM IIB HMM. Reason: The myosin motor domain binds and hydrolyzes ATP; actin-activated MgATPase activity of NM IIB is directly measured. Supporting Evidence: PMID:15845534 Comparison of the actin-activated MgATPase activity and in vitro motility shows that mutation of residues Asn-97 and Arg-709 in HMM II-B |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding from InterPro. Reason: The myosin motor domain binds and hydrolyzes ATP; actin-activated MgATPase activity of NM IIB is directly measured. Supporting Evidence: PMID:15845534 we characterized the in vitro activity of mutated and wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C |
| GO:0005524 ATP binding | NAS PMID:7782316 Neuronal cell expression of inserted isoforms of vertebrate ... | ACCEPT | Summary: ATP binding, author statement (inserts near the ATP binding region). Reason: The myosin motor domain binds and hydrolyzes ATP; actin-activated MgATPase activity of NM IIB is directly measured. Supporting Evidence: PMID:7782316 they contain inserted cassettes of amino acids near the ATP binding region and/or near the actin binding region |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | MARK AS OVER ANNOTATED | Summary: Detected in a mass-spectrometry catalogue of isolated human sperm nuclei. Reason: A single high-throughput proteomic detection in sperm nuclear preparations is weak evidence for nuclear residence of an abundant cytoplasmic cytoskeletal motor; NM IIB acts on cortical and cytoplasmic actin. Supporting Evidence: PMID:21630459 With this approach, 403 different proteins have been identified from the isolated sperm nuclei. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm (IBA). Reason: NM IIB is a cytoplasmic motor associated with the actin cytoskeleton, cortex and stress fibers. Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex |
| GO:0005737 cytoplasm | IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul... | ACCEPT | Summary: Cytoplasmic immunolocalization of myosin-IIB. Reason: NM IIB is a cytoplasmic motor associated with the actin cytoskeleton, cortex and stress fibers. Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm (IEA). Reason: NM IIB is a cytoplasmic motor associated with the actin cytoskeleton, cortex and stress fibers. Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. |
| GO:0005819 spindle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Spindle, transferred from orthologs. Reason: During mitosis NM IIB concentrates in the cortex and cleavage furrow, not on the microtubule spindle; spindle localization is not supported for human MYH10. Supporting Evidence: PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate. |
| GO:0005829 cytosol | IMP PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | ACCEPT | Summary: Cytosolic myosin pool, from the collagen synthesis study. Reason: NM IIB exists in soluble (folded, unassembled) and filamentous cytoplasmic pools; cytosol is a correct location. Supporting Evidence: PMID:20603131 LARP6 interacts with nonmuscle myosin through its C-terminal domain and associates collagen mRNAs with the filaments. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5668932 | ACCEPT | Summary: Cytosol, from the Reactome non-muscle myosin II complex in the PAK2-MRLC phosphorylation reaction. Reason: Consistent with cytoplasmic localization of the non-muscle myosin II complex. Supporting Evidence: Reactome:R-HSA-5668932 PAK2, activated by CDC42 or RAC1 RHO GTPases, phosphorylates myosin regulatory light chain (MRLC, MYL9 or MYL12B) of the non-muscle myosin II complex |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plasma membrane from UniProt subcellular location (cell membrane; noted in HSV-1 infection context). Reason: NM IIB is cortical and becomes surface-exposed during HSV-1 entry; plasma membrane is a peripheral, non-core location. Supporting Evidence: PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex PMID:25428876 NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry |
| GO:0005903 brush border | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Brush border, transferred from orthologs. Reason: Non-muscle myosin II is part of the terminal web beneath the epithelial brush border; tissue-specific, non-core location. |
| GO:0005938 cell cortex | IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul... | ACCEPT | Summary: Myosin-IIB in the cell cortex. Reason: Direct immunolocalization; cortical actomyosin is a major site of NM IIB function. Supporting Evidence: PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | ACCEPT | Summary: Cell cortex, transferred from orthologs. Reason: Consistent with human experimental data. Supporting Evidence: PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex |
| GO:0008360 regulation of cell shape | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of cell shape (IBA). Reason: Actomyosin contractility by NM II controls cell shape; NM IIB depletion increases cell surface area and abolishes stress fibers. Supporting Evidence: PMID:15774463 The RNAi-treated cells had increased surface areas and, unlike control cells, lacked actin stress fibers. file:human/MYH10/MYH10-uniprot.txt Cellular myosin that appears to play a role in cytokinesis, |
| GO:0009898 cytoplasmic side of plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasmic side of plasma membrane, transferred from orthologs. Reason: Consistent with cortical localization beneath the plasma membrane; non-core. Supporting Evidence: PMID:7699007 A low concentration of diffuse myosin-IIB is present in the cortex |
| GO:0009986 cell surface | IDA PMID:25428876 Nonmuscle myosin heavy chain IIb mediates herpes simplex vir... | KEEP AS NON CORE | Summary: NM IIB surface expression upon HSV-1 entry. Reason: Surface exposure is observed in the context of HSV-1 infection; not a normal core location. Supporting Evidence: PMID:25428876 a specific inhibitor of myosin light chain kinase inhibited cell surface expression of NMHC-IIB in COS-1 cells upon HSV-1 entry |
| GO:0016459 myosin complex | IEA GO_REF:0000120 | ACCEPT | Summary: Myosin complex (IEA). Reason: MYH10 is the heavy chain of the hexameric non-muscle myosin IIB (two heavy chains, two essential and two regulatory light chains). Supporting Evidence: file:human/MYH10/MYH10-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain |
| GO:0016459 myosin complex | NAS PMID:7499478 Cloning of the cDNA encoding human nonmuscle myosin heavy ch... | ACCEPT | Summary: Myosin complex, from the cloning of human NMHC-B. Reason: MYH10 is the heavy chain of the hexameric non-muscle myosin IIB (two heavy chains, two essential and two regulatory light chains). Supporting Evidence: PMID:7499478 we present the derived sequence of the remaining 1303 amino acids |
| GO:0016460 myosin II complex | IBA GO_REF:0000033 | ACCEPT | Summary: Myosin II complex (IBA). Reason: MYH10 is the heavy chain of the hexameric non-muscle myosin IIB (two heavy chains, two essential and two regulatory light chains). This is the precise complex term. Supporting Evidence: file:human/MYH10/MYH10-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain PMID:24072716 Although each NM II is capable of forming bipolar filaments |
| GO:0016460 myosin II complex | IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: Full-length NM IIB expressed and purified with its light chains. Reason: MYH10 is the heavy chain of the hexameric non-muscle myosin IIB (two heavy chains, two essential and two regulatory light chains). Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP. |
| GO:0016460 myosin II complex | IEA GO_REF:0000120 | ACCEPT | Summary: Myosin II complex (IEA). Reason: MYH10 is the heavy chain of the hexameric non-muscle myosin IIB (two heavy chains, two essential and two regulatory light chains). Supporting Evidence: file:human/MYH10/MYH10-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | ACCEPT | Summary: Lamellipodium from UniProt subcellular location. Reason: NM IIB functions in lamellipodial extension and cytoskeletal reorganization during cell spreading. Supporting Evidence: file:human/MYH10/MYH10-uniprot.txt part but not the margins of spreading cells), and lamellipodial |
| GO:0030048 actin filament-based movement | IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ... | ACCEPT | Summary: In vitro motility of NM IIB HMM moving actin filaments. Reason: Direct in vitro motility measurements show NM IIB drives actin filament-based movement. Supporting Evidence: PMID:15845534 Comparison of the actin-activated MgATPase activity and in vitro motility shows that mutation of residues Asn-97 and Arg-709 in HMM II-B |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Axon (orthology transfer). Reason: Non-muscle myosin IIB is the predominant myosin II in the nervous system and is found in neuronal processes, growth cones and dendritic spines; these are valid but tissue-context locations, kept as non-core. Supporting Evidence: PMID:19607793 Myosin IIB is the predominant Myosin II motor expressed in the nervous system |
| GO:0030426 growth cone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Growth cone (orthology transfer). Reason: Non-muscle myosin IIB is the predominant myosin II in the nervous system and is found in neuronal processes, growth cones and dendritic spines; these are valid but tissue-context locations, kept as non-core. Supporting Evidence: PMID:19607793 Myosin IIB is the predominant Myosin II motor expressed in the nervous system |
| GO:0030496 midbody | IDA PMID:11029059 Conditional expression of a truncated fragment of nonmuscle ... | KEEP AS NON CORE | Summary: GFP-NMHC II-B at the cytokinetic ring during mitosis in HeLa cells. Reason: The paper shows GFP-NMHC II-B in the cytokinetic ring; midbody residence at late cytokinesis is plausible but the cleavage furrow is the better-supported site. Supporting Evidence: PMID:11029059 GFP-tagged full-length NMHC II-A or II-B, but not delta N592, were localized to the cytokinetic ring during mitosis |
| GO:0031032 actomyosin structure organization | IBA GO_REF:0000033 | ACCEPT | Summary: Actomyosin structure organization (IBA). Reason: NM IIB assembles into bipolar filaments that cross-link and contract actin, organizing actomyosin structures such as stress fibers. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. PMID:15774463 The RNAi-treated cells had increased surface areas and, unlike control cells, lacked actin stress fibers. |
| GO:0031032 actomyosin structure organization | IEA GO_REF:0000117 | ACCEPT | Summary: Actomyosin structure organization (ARBA). Reason: NM IIB assembles into bipolar filaments that cross-link and contract actin, organizing actomyosin structures such as stress fibers. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0031032 actomyosin structure organization | IMP PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: Full-length NM IIB filaments cross-link actin into dense actomyosin networks. Reason: NM IIB assembles into bipolar filaments that cross-link and contract actin, organizing actomyosin structures such as stress fibers. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0031594 neuromuscular junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuromuscular junction (orthology transfer). Reason: Tissue-context location transferred from rodent evidence; non-core. |
| GO:0032154 cleavage furrow | IDA PMID:11029059 Conditional expression of a truncated fragment of nonmuscle ... | ACCEPT | Summary: GFP-NMHC II-B localizes to the cytokinetic ring. Reason: Direct localization during cytokinesis. Supporting Evidence: PMID:11029059 GFP-tagged full-length NMHC II-A or II-B, but not delta N592, were localized to the cytokinetic ring during mitosis |
| GO:0032154 cleavage furrow | IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul... | ACCEPT | Summary: Myosin-II isozymes concentrate in the cleavage furrow. Reason: Direct immunolocalization. Supporting Evidence: PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate. |
| GO:0032982 myosin filament | IBA GO_REF:0000033 | ACCEPT | Summary: Myosin filament (IBA). Reason: NM IIB forms bipolar filaments. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments |
| GO:0035613 RNA stem-loop binding | IDA PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | REMOVE | Summary: Myosin IIB co-purifies with collagen mRNA 5' stem-loop via LARP6. Reason: The IDA derives from co-purification of myosin IIB with collagen mRNA 5' stem-loop complexes. The full text states that LARP6 is the only direct 5'SL binder and that myosin is tethered through protein-protein interaction with LARP6, so direct RNA binding by MYH10 is not supported; the association is indirect. Supporting Evidence: PMID:20603131 Since LARP6 is the only protein which directly binds 5′SL 16, it is likely that nonmuscle myosin had been tethered to the 5′SL by the protein-protein interaction with LARP6. PMID:20603131 LARP6 interacts with nonmuscle myosin through its C-terminal domain and associates collagen mRNAs with the filaments. |
| GO:0042641 actomyosin | IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: Actomyosin networks formed by NM IIB filaments and actin. Reason: NM IIB is a component of actomyosin assemblies (stress fibers, contractile networks). Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0042641 actomyosin | IEA GO_REF:0000117 | ACCEPT | Summary: Actomyosin (ARBA). Reason: NM IIB is a component of actomyosin assemblies (stress fibers, contractile networks). Supporting Evidence: PMID:7699007 Myosin-IIB is also concentrated in spots along perinuclear stress fibers. |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuron projection (orthology transfer). Reason: Non-muscle myosin IIB is the predominant myosin II in the nervous system and is found in neuronal processes, growth cones and dendritic spines; these are valid but tissue-context locations, kept as non-core. Supporting Evidence: PMID:19607793 By immunocytochemistry, Myosin IIB localizes to the leading process of migrating CGNs in vitro and in vivo |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body (orthology transfer). Reason: Non-muscle myosin IIB is the predominant myosin II in the nervous system and is found in neuronal processes, growth cones and dendritic spines; these are valid but tissue-context locations, kept as non-core. Supporting Evidence: PMID:19607793 Myosin IIB is the predominant Myosin II motor expressed in the nervous system |
| GO:0043197 dendritic spine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendritic spine (orthology transfer). Reason: Non-muscle myosin IIB is the predominant myosin II in the nervous system and is found in neuronal processes, growth cones and dendritic spines; these are valid but tissue-context locations, kept as non-core. Supporting Evidence: PMID:30123108 Myosin IIb localizes to the base of mushroom spine heads |
| GO:0043531 ADP binding | IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ... | KEEP AS NON CORE | Summary: Transient kinetics of NM IIB HMM show high-affinity ADP binding. Reason: ADP binding is an intrinsic step of the myosin ATPase cycle (strong ADP affinity underlies tension maintenance); correct but a component of the motor activity rather than a separate function. Supporting Evidence: PMID:15845534 an extremely tight affinity of HMM for ADP and a very slow release of ADP from acto-HMM |
| GO:0045055 regulated exocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulated exocytosis (orthology transfer). Reason: Mouse genetic evidence implicates NM IIB in regulated exocytosis/vesicle fusion (e.g. in secretory cells); plausible via cortical actomyosin, but tissue-specific and not a core function. |
| GO:0045055 regulated exocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulated exocytosis (sequence similarity). Reason: Mouse genetic evidence implicates NM IIB in regulated exocytosis/vesicle fusion (e.g. in secretory cells); plausible via cortical actomyosin, but tissue-specific and not a core function. |
| GO:0046718 symbiont entry into host cell | IDA PMID:25428876 Nonmuscle myosin heavy chain IIb mediates herpes simplex vir... | KEEP AS NON CORE | Summary: NM IIB mediates HSV-1 entry. Reason: Host factor exploited by HSV-1; valid but non-core. Supporting Evidence: PMID:25428876 NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry |
| GO:0048027 mRNA 5'-UTR binding | IDA PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | REMOVE | Summary: mRNA 5'-UTR binding inferred from myosin association with collagen mRNA 5'SL complexes. Reason: The IDA derives from co-purification of myosin IIB with collagen mRNA 5' stem-loop complexes. The full text states that LARP6 is the only direct 5'SL binder and that myosin is tethered through protein-protein interaction with LARP6, so direct RNA binding by MYH10 is not supported; the association is indirect. Supporting Evidence: PMID:20603131 Since LARP6 is the only protein which directly binds 5′SL 16, it is likely that nonmuscle myosin had been tethered to the 5′SL by the protein-protein interaction with LARP6. |
| GO:0050714 positive regulation of protein secretion | IMP PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | MARK AS OVER ANNOTATED | Summary: Myosin inhibition impairs secretion of heterotrimeric type I collagen. Reason: Perturbations were pharmacological (ML-7, blebbistatin) and affect all NM II paralogs; the effect is specific to coordinated synthesis of collagen alpha1/alpha2 chains, while general secretion (fibronectin) was unaffected. Positive regulation of protein secretion over-generalizes a collagen-translation-coupling role. Supporting Evidence: PMID:20603131 The secretion of fibronectin was not affected, suggesting that the general machinery for protein secretion was intact. |
| GO:0051015 actin filament binding | IBA GO_REF:0000033 | ACCEPT | Summary: Actin filament binding (IBA). Reason: NM IIB motor domains bind actin filaments in an ATP-regulated manner; full-length NM IIB has the strongest actin binding among the human NM II paralogs. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0051015 actin filament binding | IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ... | ACCEPT | Summary: Actin-activated ATPase and motility of NM IIB HMM require actin filament binding. Reason: NM IIB motor domains bind actin filaments in an ATP-regulated manner; full-length NM IIB has the strongest actin binding among the human NM II paralogs. Supporting Evidence: PMID:15845534 Comparison of the actin-activated MgATPase activity and in vitro motility shows that mutation of residues Asn-97 and Arg-709 in HMM II-B |
| GO:0051015 actin filament binding | IEA GO_REF:0000002 | ACCEPT | Summary: Actin filament binding (InterPro). Reason: NM IIB motor domains bind actin filaments in an ATP-regulated manner; full-length NM IIB has the strongest actin binding among the human NM II paralogs. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. |
| GO:0051015 actin filament binding | IMP PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: Full-length NM IIB filaments bind actin (contributes_to). Reason: NM IIB motor domains bind actin filaments in an ATP-regulated manner; full-length NM IIB has the strongest actin binding among the human NM II paralogs. Supporting Evidence: PMID:24072716 Under the conditions tested, the NM IIB paralog had the greatest tendency to bind actin (89% bound; see Table 2 ) and accordingly, the greatest tendency to cross-link actin. PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: Detected in prostatic-secretion exosome proteomics. Reason: Abundant cytoskeletal proteins are routinely captured in exosome proteomes; this does not indicate a function of NM IIB in exosomes. |
| GO:0070382 exocytic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Exocytic vesicle (orthology transfer). Reason: Transferred from rodent evidence associating NM IIB with exocytic vesicles in secretory cells; plausible but non-core. |
| GO:0070382 exocytic vesicle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Exocytic vesicle (sequence similarity). Reason: Transferred from rodent evidence associating NM IIB with exocytic vesicles in secretory cells; plausible but non-core. |
| GO:0097513 myosin II filament | IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin... | ACCEPT | Summary: NM IIB forms bipolar myosin II filaments. Reason: Direct EM of filaments of purified full-length NM IIB. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments |
| GO:0097513 myosin II filament | IEA GO_REF:0000117 | ACCEPT | Summary: Myosin II filament (ARBA). Reason: Consistent with direct evidence. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments |
| GO:0098794 postsynapse | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Postsynapse (ARBA). Reason: NM IIB is enriched in dendritic spines, where its contractility shapes the spine actin cytoskeleton; a valid neuronal specialization, kept as non-core. Supporting Evidence: PMID:30123108 Myosin IIb localizes to the base of mushroom spine heads |
| GO:0098871 postsynaptic actin cytoskeleton | IDA PMID:30123108 ASD-Associated De Novo Mutations in Five Actin Regulators Sh... | KEEP AS NON CORE | Summary: Expressed MYH10 enriches in dendritic spines of hippocampal neurons. Reason: NM IIB is enriched in dendritic spines, where its contractility shapes the spine actin cytoskeleton; a valid neuronal specialization, kept as non-core. Supporting Evidence: PMID:30123108 Common for all the proteins studied was the enrichment in dendritic spines. PMID:30123108 Myosin IIb localizes to the base of mushroom spine heads |
| GO:0098871 postsynaptic actin cytoskeleton | IMP PMID:30123108 ASD-Associated De Novo Mutations in Five Actin Regulators Sh... | KEEP AS NON CORE | Summary: MYH10 (and an ASD-associated mutant) localization in dendritic spines. Reason: NM IIB is enriched in dendritic spines, where its contractility shapes the spine actin cytoskeleton; a valid neuronal specialization, kept as non-core. Supporting Evidence: PMID:30123108 Common for all the proteins studied was the enrichment in dendritic spines. |
| GO:0098974 postsynaptic actin cytoskeleton organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Postsynaptic actin cytoskeleton organization (orthology transfer from mouse). Reason: NM IIB is enriched in dendritic spines, where its contractility shapes the spine actin cytoskeleton; a valid neuronal specialization, kept as non-core. Supporting Evidence: PMID:30123108 Simultaneously, myosin IIb-induced contractility enhances the dynamics of actin filaments on the spine surface, thus facilitating the fast fine-tuning of spine shape |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glutamatergic synapse (orthology transfer). Reason: NM IIB is enriched in dendritic spines, where its contractility shapes the spine actin cytoskeleton; a valid neuronal specialization, kept as non-core. Supporting Evidence: PMID:30123108 Myosin IIb localizes to the base of mushroom spine heads |
| GO:0099500 vesicle fusion to plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Vesicle fusion to plasma membrane (orthology transfer). Reason: Mouse genetic evidence implicates NM IIB in regulated exocytosis/vesicle fusion (e.g. in secretory cells); plausible via cortical actomyosin, but tissue-specific and not a core function. |
| GO:0099500 vesicle fusion to plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Vesicle fusion to plasma membrane (sequence similarity). Reason: Mouse genetic evidence implicates NM IIB in regulated exocytosis/vesicle fusion (e.g. in secretory cells); plausible via cortical actomyosin, but tissue-specific and not a core function. |
| GO:0001764 neuron migration | ISS PMID:15034141 A point mutation in the motor domain of nonmuscle myosin II-... | NEW | Summary: Non-muscle myosin IIB generates actomyosin contractile force in migrating neurons, driving somal/nuclear translocation. Reason: Mouse NMHC II-B motor-domain mutants show defective migration of cerebellar granule, facial and pontine neurons, and myosin II inhibition blocks forward nuclear translocation in migrating neurons, with NM IIB the predominant neuronal myosin II localized to the leading process. MYH10 does work in the process (it is the force-generating motor), so this passes the participation test; mouse Myh10 carries this term by IMP, but human MYH10 lacks it because rodent acts_upstream_of_or_within annotations are not propagated. Evidence is from mouse orthologue. Supporting Evidence: PMID:15034141 These studies demonstrate that NMHC II-B is particularly important for normal migration of distinct groups of neurons during mouse brain development. PMID:15034141 Analysis of the brains of homozygous mutant mice showed significant defects in neuronal migration involving granule cells in the cerebellum, the facial neurons, and the anterior extramural precerebellar migratory stream, including the pontine neurons. PMID:19607793 By immunocytochemistry, Myosin IIB localizes to the leading process of migrating CGNs in vitro and in vivo PMID:19607793 Myosin IIB is the predominant Myosin II motor expressed in the nervous system PMID:15958735 The forward movement of the nucleus is blocked by blebbistatin, a specific inhibitor of nonmuscle myosin II. |
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Download this section (compressed HTML)Q: Is NM IIB specifically (versus NM IIA) the myosin II paralog that drives rear-of-soma contraction during nucleokinesis in cortical and MGE-derived neurons, and should human MYH10 carry nuclear migration (GO:0007097) in addition to neuron migration?
Suggested experts: neuronal migration cell biologists, myosin II biophysicists
Q: Should the collagen-mRNA association of NM IIB be represented as an indirect role (e.g. via LARP6) in regulation of translation rather than as direct RNA binding?
Suggested experts: GO RNA-binding editors
Experiment: Paralog-specific knockdown or conditional deletion of Myh10 versus Myh9 in migrating cortical and cerebellar neurons with live imaging of nucleus-centrosome dynamics, to determine which myosin II paralog provides the rear contraction for nucleokinesis.
Type: genetic perturbation with live imaging
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