MYH9

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000146 microfilament motor activity	IBA GO_REF:0000033	ACCEPT	Summary: Microfilament motor activity (IBA) is the defining activity of the class II myosin heavy chain family; MYH9 sits squarely inside the conventional myosin II clade. Reason: MYH9 is the heavy chain of non-muscle myosin IIA, an actin-activated Mg-ATPase that translocates actin filaments; recombinant NM IIA heavy meromyosin hydrolyses ATP and moves actin in in vitro motility assays, and disease mutations in the head reduce both. This is the defining core activity of the gene. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate PMID:24072716 Nonmuscle myosin IIs (NM IIs) are a group of molecular motors involved in a wide variety of cellular processes including cytokinesis, migration, and control of cell morphology file:human/MYH9/MYH9-uniprot.txt Cellular myosin that appears to play a role in cytokinesis,
GO:0000146 microfilament motor activity	IDA PMID:12237319 Mutations in human nonmuscle myosin IIA found in patients wi...	ACCEPT	Summary: Direct in vitro demonstration: recombinant NM IIA HMM has actin-activated MgATPase activity and translocates actin filaments; MYH9-RD mutations impair both. Reason: MYH9 is the heavy chain of non-muscle myosin IIA, an actin-activated Mg-ATPase that translocates actin filaments; recombinant NM IIA heavy meromyosin hydrolyses ATP and moves actin in in vitro motility assays, and disease mutations in the head reduce both. This is the defining core activity of the gene. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate PMID:12237319 This heavy meromyosin has only 4% of the maximal MgATPase activity of wild type and does not translocate actin filaments in an in vitro motility assay
GO:0000146 microfilament motor activity	IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ...	ACCEPT	Summary: Enzymology paper on disease-associated nonmuscle myosin II mutations; the abstract foregrounds II-B and II-C but names the homologous human NMHC II-A mutations, and the curator annotated MYH9 from the full text. The activity is unquestionably correct for MYH9. Reason: MYH9 is the heavy chain of non-muscle myosin IIA, an actin-activated Mg-ATPase that translocates actin filaments; recombinant NM IIA heavy meromyosin hydrolyses ATP and moves actin in in vitro motility assays, and disease mutations in the head reduce both. This is the defining core activity of the gene. Deferring to the curator for the specific II-A data, as the cached record is abstract-only. Supporting Evidence: PMID:15845534 R702C and N93K in human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate
GO:0000146 microfilament motor activity	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Full-length human NM IIA purified with its light chains (contributes_to, reflecting that the motor activity is a property of the hexameric heavy/light chain complex) forms filaments that bind and act on actin. Reason: MYH9 is the heavy chain of non-muscle myosin IIA, an actin-activated Mg-ATPase that translocates actin filaments; recombinant NM IIA heavy meromyosin hydrolyses ATP and moves actin in in vitro motility assays, and disease mutations in the head reduce both. This is the defining core activity of the gene. The contributes_to qualifier appropriately reflects that the activity requires the essential and regulatory light chains. Supporting Evidence: PMID:24072716 Nonmuscle myosin IIs (NM IIs) are a group of molecular motors involved in a wide variety of cellular processes including cytokinesis, migration, and control of cell morphology PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP
GO:0000902 cell morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cell morphogenesis via Ensembl ortholog projection. Myosin IIA contractility controls cell shape and spreading, but this is a broad downstream consequence of the motor activity. Reason: Supported in general terms (UniProt: role in cell shape), but it is a high-level, pleiotropic outcome of actomyosin contractility rather than a specific process MYH9 executes. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Cellular myosin that appears to play a role in cytokinesis, PMID:24072716 Nonmuscle myosin IIs (NM IIs) are a group of molecular motors involved in a wide variety of cellular processes including cytokinesis, migration, and control of cell morphology
GO:0001525 angiogenesis	IDA PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	KEEP AS NON CORE	Summary: Angiogenesis based on endothelial knockdown/inhibition blocking nucleolin-dependent capillary tube formation. Reason: MYH9 knockdown or myosin inhibition blocked the angiogenic function of cell-surface nucleolin in endothelial cells. This is a context-specific tissue-level consequence of cytoskeletal function, not a core role. Supporting Evidence: PMID:16403913 Knocking down endogenous MyH9, specifically inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts the organization of cell-surface nucleolin and inhibits its angiogenic function
GO:0001618 virus receptor activity	IDA PMID:20944748 Non-muscle myosin IIA is a functional entry receptor for her...	KEEP AS NON CORE	Summary: Virus receptor activity: NMHC-IIA acts as an entry receptor for HSV-1 glycoprotein B (microbial-infection function recorded by UniProt). Reason: Well supported by gain- and loss-of-function and antibody-blocking experiments, and reproduced by UniProt. It is a host-pathogen exploitation of a cytoskeletal protein that becomes surface exposed during entry, not a physiological function of MYH9, so it is retained as non-core. Supporting Evidence: PMID:20944748 Here we show that non-muscle myosin heavy chain IIA (NMHC-IIA), a subunit of non-muscle myosin IIA (NM-IIA), functions as an HSV-1 entry receptor by interacting with gB PMID:20944748 Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry file:human/MYH9/MYH9-uniprot.txt Acts as a receptor for herpes simplex
GO:0001725 stress fiber	IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	ACCEPT	Summary: Stress fiber localization (IDA) from the menin interaction study; consistent with extensive independent evidence. Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. The cached record is abstract-only, but stress-fiber localization of NMIIA is well established by other annotations here. Supporting Evidence: PMID:14508515 confirmed by glutathione-S-transferase pulldown assays, by coimmunoprecipitation, and by actin selection of myosin PMID:14706930 The results indicate that MYH9 colocalizes with actin stress fibers
GO:0001725 stress fiber	IDA PMID:14706930 Expression of non-muscle type myosin heavy polypeptide 9 (MY...	ACCEPT	Summary: EGFP-MYH9 colocalizes with actin stress fibers in HeLa cells. Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. Supporting Evidence: PMID:14706930 The results indicate that MYH9 colocalizes with actin stress fibers
GO:0001725 stress fiber	IDA PMID:15774463 Vertebrate nonmuscle myosin II isoforms rescue small interfe...	ACCEPT	Summary: Stress fiber localization from the NMHC isoform cytokinesis rescue study (GFP-NMHC II-A in COS-7 cells). Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. Abstract-only cached record; accepted in line with the consistent localization evidence. Supporting Evidence: PMID:11029059 Confocal microscopy indicated that the GFP fusion proteins of full-length NMHC II-A, II-B, and delta N592 were localized to stress fibers PMID:14706930 The results indicate that MYH9 colocalizes with actin stress fibers
GO:0001725 stress fiber	IDA PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	ACCEPT	Summary: Stress fiber localization reported in endothelial cells in the nucleolin study. Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. Supporting Evidence: PMID:14706930 The results indicate that MYH9 colocalizes with actin stress fibers PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells
GO:0001725 stress fiber	IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul...	ACCEPT	Summary: Antibody staining shows myosin-IIA concentrated in spots along stress fibers in cultured human cells. Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. Supporting Evidence: PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells
GO:0001725 stress fiber	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (ortholog) annotation to stress fiber; consistent with direct human evidence. Reason: Myosin IIA is a major component of contractile actin stress fibers, where bipolar filaments are distributed in periodic spots along the fibers. Supporting Evidence: PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells PMID:14706930 The results indicate that MYH9 colocalizes with actin stress fibers
GO:0001726 ruffle	IDA PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	KEEP AS NON CORE	Summary: Ruffle localization in endothelial cells (nucleolin study). Reason: Plausible peripheral actin-rich location, but a transient, cell-type-specific site; not a principal location of NMIIA, which is enriched in stress fibers and the contractile ring. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0001772 immunological synapse	IDA PMID:15064761 A single class II myosin modulates T cell motility and stopp...	KEEP AS NON CORE	Summary: Immunological synapse localization in T cells. Reason: MyH9 is the only class II myosin in T cells; the paper found it dispensable for synapse formation, with its principal role in uropod maintenance and motility. A synapse location is plausible but minor, so retained as non-core. Supporting Evidence: PMID:15064761 MyH9 function is required for maintenance of the uropod and for T cell motility but is dispensable for synapse formation PMID:15064761 nonmuscle myosin heavy chain IIA, or MyH9, is the only class II myosin expressed in T cells and is associated with the uropod during crawling
GO:0001772 immunological synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic ortholog projection of immunological synapse localization. Reason: As for the IDA annotation: plausible but minor, cell-type-specific location. Supporting Evidence: PMID:15064761 MyH9 function is required for maintenance of the uropod and for T cell motility but is dispensable for synapse formation
GO:0001778 plasma membrane repair	IDA PMID:27325790 A Rab3a-dependent complex essential for lysosome positioning...	KEEP AS NON CORE	Summary: Plasma membrane repair: NMHC-IIA, as a Rab3a effector, is needed for peripheral lysosome positioning and lysosome exocytosis that reseals membrane damage. Reason: Supported by knockdown data in the cited full-text paper. The motor contributes by positioning lysosomes at the periphery; a specialised, context-specific role. Supporting Evidence: PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis PMID:27325790 Lysosome exocytosis plays a major role in resealing plasma membrane (PM) disruptions
GO:0001931 uropod	IDA PMID:15064761 A single class II myosin modulates T cell motility and stopp...	ACCEPT	Summary: Uropod localization in migrating T cells, where MyH9 is required to maintain the uropod. Reason: Direct localization plus functional requirement in leukocytes, where MYH9 is the only class II myosin. Supporting Evidence: PMID:15064761 MyH9 function is required for maintenance of the uropod and for T cell motility but is dispensable for synapse formation PMID:15064761 nonmuscle myosin heavy chain IIA, or MyH9, is the only class II myosin expressed in T cells and is associated with the uropod during crawling
GO:0001931 uropod	IEA GO_REF:0000107	ACCEPT	Summary: Electronic ortholog projection of uropod localization; consistent with human T cell data. Reason: Consistent with direct evidence in human T cells. Supporting Evidence: PMID:15064761 nonmuscle myosin heavy chain IIA, or MyH9, is the only class II myosin expressed in T cells and is associated with the uropod during crawling
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	MARK AS OVER ANNOTATED	Summary: RNA binding from a high-throughput mRNA interactome capture (HEK293). Reason: MYH9 has no known RNA-binding domain or characterised RNA-binding function; detection of an abundant cytoskeletal protein in UV-crosslink/oligo(dT) interactome capture is insufficient to assert an RNA-binding molecular function.
GO:0003774 cytoskeletal motor activity	IEA GO_REF:0000002	ACCEPT	Summary: Cytoskeletal motor activity from InterPro myosin head domain mapping; correct but more general than microfilament motor activity. Reason: Accurate parent of GO:0000146; acceptable for an electronic annotation. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate file:human/MYH9/MYH9-uniprot.txt Cellular myosin that appears to play a role in cytokinesis,
GO:0003774 cytoskeletal motor activity	NAS PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	ACCEPT	Summary: Cytoskeletal motor activity (NAS) in the context of chemokine receptor-associated myosin in T lymphocytes. Reason: Correct general statement of the motor function of NMIIA. Supporting Evidence: PMID:12421915 CXCR4 and motor protein nonmuscle myosin H chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin L chain
GO:0003779 actin binding	IDA PMID:15065866 Two-headed binding of the unphosphorylated nonmuscle heavy m...	ACCEPT	Summary: Actin binding: both heads of NM IIA HMM bind actin filaments with nanomolar affinity. Reason: Directly measured; actin filament binding is intrinsic to the motor cycle. Supporting Evidence: PMID:15065866 both heads of either thiophosphorylated or unphosphorylated heavy meromyosin bind very strongly to actin (K(d) < 10 nM) in the presence or absence of ADP
GO:0005178 integrin binding	IDA PMID:10822899 Protein complexes involving alpha v beta 3 integrins, nonmus...	KEEP AS NON CORE	Summary: Integrin binding based on thrombospondin-induced co-association of NMHC-A with alpha v beta 3 integrin and FAK in smooth muscle cells. Reason: Co-immunoprecipitation shows complex formation, not direct binding, and the link between myosin II and integrins is normally indirect via talin/actin at adhesions. Retained as a non-core, context-specific association; not a defining activity of MYH9. Supporting Evidence: PMID:10822899 TSP treatment elicited a time-dependent association of nonmuscle myosin heavy chain-A (NMHC-A) with alpha v beta 3 integrins
GO:0005515 protein binding	IPI PMID:10822899 Protein complexes involving alpha v beta 3 integrins, nonmus...	MODIFY	Summary: Protein binding with ITGB3 (alpha v beta 3 integrin) from thrombospondin-induced co-immunoprecipitation. Reason: Generic protein binding is uninformative. The partner is an integrin beta subunit, and the same paper underlies the integrin binding row; GO:0005178 integrin binding is the more informative term, although the association is likely indirect (see integrin binding row). Proposed replacements: integrin binding Supporting Evidence: PMID:10822899 TSP treatment elicited a time-dependent association of nonmuscle myosin heavy chain-A (NMHC-A) with alpha v beta 3 integrins
GO:0005515 protein binding	IPI PMID:10822899 Protein complexes involving alpha v beta 3 integrins, nonmus...	REMOVE	Summary: Protein binding with focal adhesion kinase (PTK2) from co-immunoprecipitation in TSP-treated smooth muscle cells. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:12202484 Proteomic analysis of a detergent-resistant membrane skeleto...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	REMOVE	Summary: Protein binding with menin (MEN1); TAP-MS, GST pull-down and co-IP identify NMHC II-A as a menin partner. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. The interaction characterises menin more than MYH9. Supporting Evidence: PMID:14508515 confirmed by glutathione-S-transferase pulldown assays, by coimmunoprecipitation, and by actin selection of myosin
GO:0005515 protein binding	IPI PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	REMOVE	Summary: Protein binding with menin (MEN1) isoform; same study. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:14640694 Mts1 regulates the assembly of nonmuscle myosin-IIA.	MODIFY	Summary: Protein binding with S100A4 (mts1), which binds residues 1909-1924 of the myosin-IIA heavy chain and disassembles filaments. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. Proposed replacements: S100 protein binding Supporting Evidence: PMID:14640694 we have demonstrated that mts1 binds to residues 1909-1924 of the myosin-IIA heavy chain PMID:14640694 mts1 inhibits the assembly of myosin-IIA monomers into filaments and promotes the disassembly of myosin-IIA filaments into monomers
GO:0005515 protein binding	IPI PMID:15171681 Heterodimeric interaction and interfaces of S100A1 and S100P...	MODIFY	Summary: Protein binding with S100P; S100P binds a C-terminal fragment of non-muscle myosin A. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. Proposed replacements: S100 protein binding Supporting Evidence: PMID:15171681 reduced by up to 50% the binding of S100P to a recombinant C-terminal fragment of non-muscle myosin A, one of its target molecules
GO:0005515 protein binding	IPI PMID:15479433 Interaction of soluble CD163 with activated T lymphocytes in...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:15479433 Interaction of soluble CD163 with activated T lymphocytes in...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:16186248 Signaling via the angiotensin-converting enzyme results in t...	REMOVE	Summary: Protein binding with ACE (isoform 1) in endothelial cells. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. Supporting Evidence: PMID:16186248 These data indicate that the interaction of ACE with MYH9 determines ACE shedding and is modulated by phosphorylation processes
GO:0005515 protein binding	IPI PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	REMOVE	Summary: Protein binding with nucleolin; MYH9 links cell-surface nucleolin to the cytoskeleton in endothelial cells. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0005515 protein binding	IPI PMID:17925381 Supervillin slows cell spreading by facilitating myosin II a...	REMOVE	Summary: Protein binding with supervillin, which binds the S2 domain of NM IIA and IIB. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. Supporting Evidence: PMID:17925381 binds directly to the subfragment 2 domains of nonmuscle myosin IIA and myosin IIB
GO:0005515 protein binding	IPI PMID:18504258 Use of fluorescence-activated vesicle sorting for isolation ...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:20421509 Phenothiazines inhibit S100A4 function by inducing protein o...	MODIFY	Summary: Protein binding with S100A4 in a study of phenothiazine inhibitors of the S100A4/myosin-IIA interaction. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. Proposed replacements: S100 protein binding Supporting Evidence: PMID:20421509 S100A4, a member of the S100 family of Ca(2+)-binding proteins, regulates carcinoma cell motility via interactions with myosin-IIA
GO:0005515 protein binding	IPI PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen.	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:20936779 A human MAP kinase interactome.	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:22229724 Application of the wheat-germ cell-free translation system t...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:22460785 Crystal structure of the S100A4-nonmuscle myosin IIA tail fr...	MODIFY	Summary: Protein binding with S100A4; crystal structure of S100A4 with a 45-residue NMIIA heavy chain fragment. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. Proposed replacements: S100 protein binding Supporting Evidence: PMID:22460785 It binds to the nonmuscle myosin IIA (NMIIA) tail near the assembly competence domain (ACD) promoting filament disassembly
GO:0005515 protein binding	IPI PMID:22483112 Asymmetric mode of Ca²⁺-S100A4 interaction with nonmuscle my...	MODIFY	Summary: Protein binding with S100A4; NMR structure of the S100A4 dimer bound to the NMIIA tail. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. Proposed replacements: S100 protein binding Supporting Evidence: PMID:22483112 Our NMR structure shows that an S100A4 dimer binds to a single myosin heavy chain in an asymmetrical configuration
GO:0005515 protein binding	IPI PMID:22693546 Sequence-specific binding of recombinant Zbed4 to DNA: insig...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:23100250 Constitutive turnover of phosphorylation at Thr-412 of human...	REMOVE	Summary: Protein binding with coronin-1 (CORO1A) from a phosphorylation turnover study. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln...	REMOVE	Summary: Protein binding with GRB2 from an EGFR interactome perturbation screen. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:2732579 [Two sisters with pseudoidiopathic hypoparathyroidism presen...	MODIFY	Summary: Protein binding with RAB3A attributed to PMID:2732579, which is a wrong identifier (a 1989 Japanese case report); the intended paper is PMID:27325790 (Rab3a/Slp4-a/NMHC-IIA complex). Reason: The WITH/FROM partner (RAB3A) and the paired annotations match PMID:27325790, whose number the cited PMID truncates. On that evidence MYH9 is a Rab3a effector; GO:0031267 small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis
GO:0005515 protein binding	IPI PMID:27325790 A Rab3a-dependent complex essential for lysosome positioning...	MODIFY	Summary: Protein binding with RAB3A; NMHC-IIA was identified as a new Rab3a effector in the Rab3a/Slp4-a complex that positions lysosomes. Reason: Generic protein binding is uninformative. As a Rab3 effector MYH9 binds GTP-bound Rab3a, which is captured by GO:0031267 small GTPase binding. Proposed replacements: small GTPase binding Supporting Evidence: PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis
GO:0005515 protein binding	IPI PMID:28228547 LIMCH1 regulates nonmuscle myosin-II activity and suppresses...	REMOVE	Summary: Protein binding with LIMCH1, which binds the NM-IIA head and promotes regulatory light chain phosphorylation. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. LIMCH1 is a regulator of NM-IIA; the interaction does not define an MYH9 activity beyond generic binding. Supporting Evidence: PMID:28228547 LIMCH1 interacted with NM-IIA, but not NM-IIB, independent of the inhibition of myosin ATPase activity with blebbistatin
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	MODIFY	Summary: Protein binding with S100 family members from a quantitative S100ome fluorescence-polarization interaction screen that used an NMIIA tail peptide as a model partner. Reason: The partner is an S100 calcium-binding protein (S100A4/mts1 or a paralog) that binds the C-terminal coiled-coil/tailpiece of the MYH9 rod and regulates filament assembly. GO:0044548 S100 protein binding captures this specific, well-characterised regulatory interaction better than generic protein binding; it is a regulatory target interaction rather than core motor function. The cached record is abstract-only; partner identities (S100A2, S100A4, S100A6, S100B, S100P, etc.) come from the GOA WITH/FROM column. Proposed replacements: S100 protein binding
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:34873039 Nonmuscle myosin heavy chain IIA facilitates SARS-CoV-2 infe...	REMOVE	Summary: Protein binding with SARS-CoV-2 spike; MYH9 was reported as a host factor for pseudovirus entry interacting with S via its C-terminal region. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false. Host-factor role is not a physiological MYH9 function.
GO:0005515 protein binding	IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome...	REMOVE	Summary: Protein binding with SARS-CoV-2 spike from a large-scale virus-host interactome. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Generic protein binding from an interaction assay; uninformative. Reason: GO:0005515 protein binding is uninformative about MYH9 function. The reported interaction is not disputed, but it does not specify a molecular activity; removal does not imply the interaction is false.
GO:0005524 ATP binding	IDA PMID:15065866 Two-headed binding of the unphosphorylated nonmuscle heavy m...	ACCEPT	Summary: ATP binding by the myosin motor domain; nucleotide-dependent actin binding measured on NM IIA HMM. Reason: ATP binding and hydrolysis by the head domain drive the actomyosin cross-bridge cycle; intrinsic to the core motor function. Supporting Evidence: PMID:15065866 both heads of either thiophosphorylated or unphosphorylated heavy meromyosin bind very strongly to actin (K(d) < 10 nM) in the presence or absence of ADP PMID:15065866 The heads have high and indistinguishable affinities for ADP (K(d) around 1 microM) when bound to actin
GO:0005524 ATP binding	IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ...	ACCEPT	Summary: ATP binding from the disease-mutation enzymology study (abstract foregrounds II-B/II-C; curator annotated MYH9 from full text). Reason: ATP binding is intrinsic to the myosin II motor domain; accepted, deferring to the curator on the specific data. Supporting Evidence: PMID:15845534 R702C and N93K in human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding from InterPro myosin motor domain mapping. Reason: Correct for a myosin motor domain. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate
GO:0005634 nucleus	IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	UNDECIDED	Summary: Nucleus localization (IDA) from the menin interaction study. Reason: The cached record is abstract-only and the abstract reports colocalization with menin in the cleavage furrow, not nuclear localization; menin itself is nuclear. Some nuclear pools of myosin II have been reported elsewhere, but I cannot verify what the curator saw, so this is left undecided rather than removed. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasm (IBA). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton). Supporting Evidence: PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells
GO:0005737 cytoplasm	IDA PMID:22693546 Sequence-specific binding of recombinant Zbed4 to DNA: insig...	ACCEPT	Summary: Cytoplasm (IDA) in retinoblastoma cells (Zbed4 interaction study). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005737 cytoplasm	IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul...	ACCEPT	Summary: Cytoplasm (IDA) by antibody staining in cultured and blood cells. Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton). Supporting Evidence: PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Cytoplasm from UniProt subcellular location mapping. Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005794 Golgi apparatus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Golgi apparatus (electronic ortholog projection). Reason: Myosin II has been implicated in Golgi carrier formation, but this is a minor, indirectly supported location for MYH9; not core.
GO:0005819 spindle	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Spindle (electronic ortholog projection). Reason: During mitosis NMIIA is cortical and concentrates in the equatorial cortex/cleavage furrow, not on the microtubule spindle. A spindle location is not supported by human evidence here. Supporting Evidence: PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate
GO:0005826 actomyosin contractile ring	IDA PMID:11029059 Conditional expression of a truncated fragment of nonmuscle ...	ACCEPT	Summary: Actomyosin contractile ring: GFP-NMHC II-A localizes to the cytokinetic ring. Reason: Core location of the cytokinetic motor. 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:0005829 cytosol	IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	ACCEPT	Summary: Cytosol (IDA). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005829 cytosol	TAS Reactome:R-HSA-5668932	ACCEPT	Summary: Cytosol (Reactome TAS). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005829 cytosol	TAS Reactome:R-HSA-9663426	ACCEPT	Summary: Cytosol (Reactome TAS). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005829 cytosol	TAS Reactome:R-HSA-9724090	ACCEPT	Summary: Cytosol (Reactome TAS). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: Cytoskeleton (UniProt subcellular location mapping). Reason: Non-muscle myosin IIA is a cytoplasmic, cytoskeleton-associated protein (UniProt: Cytoplasm, cytoskeleton).
GO:0005886 plasma membrane	EXP PMID:20944748 Non-muscle myosin IIA is a functional entry receptor for her...	KEEP AS NON CORE	Summary: Plasma membrane in the HSV-1 entry study (surface NMHC-IIA induced during entry). Reason: NMIIA is a peripheral, cortex-associated protein rather than an integral membrane protein; plasma membrane association is real in specific contexts (cortex, virus entry, receptor complexes) but cell cortex/actin cytoskeleton better describe its principal location. Supporting Evidence: PMID:20944748 Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry
GO:0005886 plasma membrane	IDA PMID:16186248 Signaling via the angiotensin-converting enzyme results in t...	KEEP AS NON CORE	Summary: Plasma membrane association with ACE in endothelial cells. Reason: NMIIA is a peripheral, cortex-associated protein rather than an integral membrane protein; plasma membrane association is real in specific contexts (cortex, virus entry, receptor complexes) but cell cortex/actin cytoskeleton better describe its principal location. Supporting Evidence: PMID:16186248 These data indicate that the interaction of ACE with MYH9 determines ACE shedding and is modulated by phosphorylation processes
GO:0005886 plasma membrane	IDA PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	KEEP AS NON CORE	Summary: Plasma membrane association with cell-surface nucleolin in endothelial cells. Reason: NMIIA is a peripheral, cortex-associated protein rather than an integral membrane protein; plasma membrane association is real in specific contexts (cortex, virus entry, receptor complexes) but cell cortex/actin cytoskeleton better describe its principal location. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plasma membrane from UniProt subcellular location mapping (Cell membrane, based on HSV-1 study). Reason: NMIIA is a peripheral, cortex-associated protein rather than an integral membrane protein; plasma membrane association is real in specific contexts (cortex, virus entry, receptor complexes) but cell cortex/actin cytoskeleton better describe its principal location. Supporting Evidence: PMID:20944748 Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry
GO:0005903 brush border	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Brush border (electronic ortholog projection). Reason: Myosin II is a component of the terminal web beneath the intestinal brush border; a tissue-specific location.
GO:0005912 adherens junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Adherens junction (electronic ortholog projection). Reason: NMIIA-containing actomyosin is associated with epithelial adherens junctions, where it tensions cadherin contacts; a context-specific location.
GO:0005925 focal adhesion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Colocalizes with focal adhesion (electronic). Reason: NMIIA-containing stress fibers terminate at focal adhesions and myosin II tension drives their maturation; colocalization is correct but peripheral to core location. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt During cell spreading, plays an important role in PMID:28228547 LIMCH1 interacted with NM-IIA, but not NM-IIB, independent of the inhibition of myosin ATPase activity with blebbistatin
GO:0005925 focal adhesion	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Colocalizes with focal adhesion (ISS). Reason: As for the electronic row; supported by gelsolin/NMMIIA colocalization at collagen adhesions. Supporting Evidence: PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:0005938 cell cortex	IEA GO_REF:0000120	ACCEPT	Summary: Cell cortex (UniProt subcellular location mapping). Reason: NMIIA forms cortical actomyosin in many cell types (e.g., cortical bundles during spreading, equatorial cortex during cytokinesis). Supporting Evidence: PMID:17925381 binds directly to the subfragment 2 domains of nonmuscle myosin IIA and myosin IIB PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate
GO:0006509 membrane protein ectodomain proteolysis	IDA PMID:16186248 Signaling via the angiotensin-converting enzyme results in t...	MODIFY	Summary: Membrane protein ectodomain proteolysis (IDA) based on MYH9 association with ACE controlling ACE shedding. Reason: MYH9 is not part of the proteolytic machinery; disrupting its association with the ACE cytoplasmic tail (CK2 inhibition, cytochalasin D) enhanced ACE shedding, implying MYH9 restrains shedding. The negative regulation term reflects the data more accurately. Proposed replacements: negative regulation of membrane protein ectodomain proteolysis Supporting Evidence: PMID:16186248 These data indicate that the interaction of ACE with MYH9 determines ACE shedding and is modulated by phosphorylation processes PMID:16186248 Cytochalasin D decreased the interaction between ACE and MYH9 and stimulated ACE shedding
GO:0006911 phagocytosis, engulfment	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Phagocytosis, engulfment (electronic ortholog projection). Reason: Myosin II contractility contributes to phagocytic cup closure and to collagen phagocytosis in fibroblasts; a context-specific process. Supporting Evidence: PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:0006911 phagocytosis, engulfment	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Phagocytosis, engulfment (ISS). Reason: As for the electronic row. Supporting Evidence: PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:0007229 integrin-mediated signaling pathway	NAS PMID:10822899 Protein complexes involving alpha v beta 3 integrins, nonmus...	MARK AS OVER ANNOTATED	Summary: Integrin-mediated signaling pathway (NAS) from co-association with alpha v beta 3 integrin and FAK. Reason: Association with an integrin/FAK complex does not show that MYH9 transduces the integrin signal; myosin II acts downstream as a force-generating effector. Over-interpretation of co-IP data. Supporting Evidence: PMID:10822899 TSP treatment elicited a time-dependent association of nonmuscle myosin heavy chain-A (NMHC-A) with alpha v beta 3 integrins
GO:0008180 COP9 signalosome	IDA PMID:18850735 Characterization of the human COP9 signalosome complex using...	MARK AS OVER ANNOTATED	Summary: Colocalizes with COP9 signalosome, from quantitative AP-MS of the CSN complex. Reason: Detection of an abundant cytoskeletal protein among CSN interactors in affinity purification is not evidence of a biologically meaningful association with the signalosome.
GO:0009898 cytoplasmic side of plasma membrane	IDA PMID:15064761 A single class II myosin modulates T cell motility and stopp...	KEEP AS NON CORE	Summary: Cytoplasmic side of plasma membrane (IDA) in T cells. Reason: Consistent with cortical association; context-specific. Supporting Evidence: PMID:15064761 nonmuscle myosin heavy chain IIA, or MyH9, is the only class II myosin expressed in T cells and is associated with the uropod during crawling
GO:0009898 cytoplasmic side of plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cytoplasmic side of plasma membrane (electronic ortholog projection). Reason: Consistent with cortical association; context-specific.
GO:0009986 cell surface	IDA PMID:20944748 Non-muscle myosin IIA is a functional entry receptor for her...	KEEP AS NON CORE	Summary: Cell surface (is_active_in) in the HSV-1 entry receptor study. Reason: Surface exposure of NMHC-IIA during HSV-1 entry is documented, but is an infection-specific state of a cytoplasmic protein. Supporting Evidence: PMID:20944748 Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry
GO:0015031 protein transport	IMP PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	MARK AS OVER ANNOTATED	Summary: Protein transport (IMP) based on MYH9-dependent translocation of nucleolin to the endothelial cell surface. Reason: MYH9 is described as a physical linker between nucleolin and the cytoskeleton that modulates nucleolin translocation; this is an indirect cytoskeletal effect in one context, and the broad term protein transport overstates MYH9's role. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0015629 actin cytoskeleton	IDA GO_REF:0000052	ACCEPT	Summary: Actin cytoskeleton (immunofluorescence curation, HPA). Reason: Core location of NMIIA. Supporting Evidence: PMID:7699007 Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells
GO:0015629 actin cytoskeleton	IDA PMID:15869600 Altered cytoskeleton organization in platelets from patients...	ACCEPT	Summary: Actin cytoskeleton in platelets; myosin IIA associates with the actin cytoskeleton, increased in MYH9-RD platelets. Reason: Core location of NMIIA. Supporting Evidence: PMID:15869600 These results demonstrate for the first time that mutations of MYH9 result in an alteration of the composition and agonist-induced reorganization of the platelet cytoskeleton
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: Membrane (HDA) from NK-cell membrane proteomics. Reason: Peripheral cortical association with membrane fractions; not an integral membrane protein.
GO:0016459 myosin complex	IEA GO_REF:0000120	ACCEPT	Summary: Myosin complex (electronic). Reason: MYH9 is the heavy chain of a hexameric myosin II complex. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain
GO:0016460 myosin II complex	IBA GO_REF:0000033	ACCEPT	Summary: Myosin II complex (IBA). Reason: MYH9 heavy chains dimerize and associate with essential and regulatory light chains to form myosin II. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain PMID:24072716 Nonmuscle myosin IIs (NM IIs) are a group of molecular motors involved in a wide variety of cellular processes including cytokinesis, migration, and control of cell morphology
GO:0016460 myosin II complex	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Myosin II complex (IDA): full-length human NM IIA purified with its light chains. Reason: Direct biochemical evidence. Supporting Evidence: 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 (electronic). Reason: Correct. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Myosin is a hexameric protein that consists of 2 heavy chain
GO:0019904 protein domain specific binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Protein domain specific binding (electronic ortholog projection; mouse gelsolin interaction). Reason: Reflects the Ca2+-dependent binding of the NMMIIA rod to gelsolin domains G4-G6; accurate but a peripheral regulatory interaction and a weakly informative term. Supporting Evidence: PMID:23325791 Gelsolin domains G4-G6 selectively require Ca(2+) to interact with NMMIIA, which is restricted to residues 1339-1899 of NMMIIA
GO:0019904 protein domain specific binding	IPI PMID:23325791 Collagen remodeling by phagocytosis is determined by collage...	KEEP AS NON CORE	Summary: Protein domain specific binding (IPI): gelsolin G4-G6 bind NMMIIA residues 1339-1899 in a Ca2+-dependent manner. Reason: Accurate description of the reported interaction; peripheral to MYH9's core function. Supporting Evidence: PMID:23325791 Gelsolin domains G4-G6 selectively require Ca(2+) to interact with NMMIIA, which is restricted to residues 1339-1899 of NMMIIA
GO:0030036 actin cytoskeleton organization	IMP PMID:15869600 Altered cytoskeleton organization in platelets from patients...	ACCEPT	Summary: Actin cytoskeleton organization (IMP) from MYH9-RD patient platelets showing altered cytoskeletal composition and agonist-induced reorganization. Reason: Myosin II contractility organizes actin into contractile bundles; the platelet mutant phenotype is consistent with this core role. Supporting Evidence: PMID:15869600 These results demonstrate for the first time that mutations of MYH9 result in an alteration of the composition and agonist-induced reorganization of the platelet cytoskeleton PMID:15869600 Isoform IIA of myosin is the only one expressed in platelets
GO:0030048 actin filament-based movement	IDA PMID:12237319 Mutations in human nonmuscle myosin IIA found in patients wi...	ACCEPT	Summary: Actin filament-based movement (IDA): NM IIA HMM translocates actin filaments in vitro. Reason: Direct measurement of the motor output. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate
GO:0030048 actin filament-based movement	IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ...	ACCEPT	Summary: Actin filament-based movement (acts upstream of or within) from the in vitro motility study of disease mutations. Reason: Correct for a myosin II motor; deferring to the curator on the II-A specific data in the full text. Supporting Evidence: PMID:15845534 R702C and N93K in human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C
GO:0030154 cell differentiation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Cell differentiation (electronic ortholog projection). Reason: Very broad term; MYH9 affects differentiation of some cell types only indirectly through cytoskeletal effects, and the term adds no functional information.
GO:0030220 platelet formation	IMP PMID:12237319 Mutations in human nonmuscle myosin IIA found in patients wi...	KEEP AS NON CORE	Summary: Platelet formation (IMP) based on MYH9-RD mutations that impair motor activity and cause giant platelets and thrombocytopenia. Reason: MYH9 is the only myosin II in platelets and megakaryocytes, and heterozygous motor-impairing mutations cause macrothrombocytopenia; this is a well-established physiological role but tissue-specific, so kept as non-core. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate PMID:15869600 Isoform IIA of myosin is the only one expressed in platelets file:human/MYH9/MYH9-deep-research-falcon.md In megakaryocytes, localized NMIIA constriction and blood-flow shear partition proplatelet extensions into platelets. file:human/MYH9/MYH9-deep-research-falcon.md NMIIA is reported to be the only NMII paralog expressed in these cells, making platelet production especially sensitive to MYH9 variants.
GO:0030224 monocyte differentiation	IEP PMID:1912569 Cellular myosin heavy chain in human leukocytes: isolation o...	MARK AS OVER ANNOTATED	Summary: Monocyte differentiation (IEP): MYH9 mRNA and protein are upregulated when myeloid cell lines are induced to differentiate. Reason: Expression changes during differentiation do not show that MYH9 participates in the differentiation process. Supporting Evidence: PMID:1912569 is upregulated in myeloid cell lines on induction from a proliferating to a differentiated state
GO:0030863 cortical cytoskeleton	IEA GO_REF:0000107	ACCEPT	Summary: Cortical cytoskeleton (electronic). Reason: Consistent with cortical actomyosin localization of NMIIA. Supporting Evidence: PMID:17925381 binds directly to the subfragment 2 domains of nonmuscle myosin IIA and myosin IIB
GO:0031032 actomyosin structure organization	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Actomyosin structure organization (IDA): NM IIA assembles into bipolar filaments upon RLC phosphorylation and binds actin. Reason: Filament assembly and actin crosslinking/contraction organize actomyosin structures; core. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP
GO:0031252 cell leading edge	IDA PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	KEEP AS NON CORE	Summary: Cell leading edge in migrating T lymphocytes, colocalized with CXCR4. Reason: In most migrating cells NMIIA is enriched at the rear/uropod; leading-edge association in this study is context-specific. Supporting Evidence: PMID:12421915 CXCR4 and motor protein nonmuscle myosin H chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin L chain
GO:0031594 neuromuscular junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuromuscular junction (electronic ortholog projection). Reason: Tissue-specific location transferred from rodent data; not a principal site of MYH9 function.
GO:0032154 cleavage furrow	IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	ACCEPT	Summary: Cleavage furrow (IDA): NMHC II-A colocalizes with menin in the cleavage furrow. Reason: Core cytokinetic location. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells
GO:0032154 cleavage furrow	IDA PMID:7699007 Differential localization of myosin-II isozymes in human cul...	ACCEPT	Summary: Cleavage furrow (IDA): myosin-II isozymes concentrate in the equatorial cortex from anaphase until separation. Reason: Core cytokinetic location. Supporting Evidence: PMID:7699007 This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate
GO:0032418 lysosome localization	IMP PMID:2732579 [Two sisters with pseudoidiopathic hypoparathyroidism presen...	KEEP AS NON CORE	Summary: Lysosome localization (IMP): NMHC-IIA, as a Rab3a effector, is required for peripheral lysosome positioning. Reason: Supported by knockdown in the intended paper; a specialised motor-dependent organelle positioning role. The cited PMID:2732579 is a wrong identifier (a 1989 Japanese case report on hypoparathyroidism); the WITH/FROM partner RAB3A and the annotation content identify the intended paper as PMID:27325790, whose number the cited id truncates. Evidence is taken from that paper. Supporting Evidence: PMID:27325790 NMHCIIA is required for lysosome positioning. PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis
GO:0032506 cytokinetic process	IMP PMID:15774463 Vertebrate nonmuscle myosin II isoforms rescue small interfe...	ACCEPT	Summary: Cytokinetic process (IMP): GFP-NMHC II-A partially rescues multinucleation caused by NMHC II-B knockdown in COS-7 cells. Reason: Myosin II drives contractile ring constriction; cytokinesis is a core cellular role of MYH9 (UniProt). The rescue assay shows II-A can support cytokinesis. Supporting Evidence: PMID:15774463 Introducing green fluorescent protein (GFP)-tagged NMHC II isoforms into II-B siRNA-treated cells resulted in reduction of multinucleation file:human/MYH9/MYH9-uniprot.txt Cellular myosin that appears to play a role in cytokinesis,
GO:0032970 regulation of actin filament-based process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Regulation of actin filament-based process (ARBA electronic). Reason: Broad but not incorrect; myosin II contractility shapes actin-based processes. Not informative beyond the core motor terms.
GO:0032982 myosin filament	IBA GO_REF:0000033	ACCEPT	Summary: Myosin filament (IBA, is_active_in). Reason: Class II myosins function as bipolar filaments; NM IIA forms such filaments. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB
GO:0032991 protein-containing complex	IDA PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	MODIFY	Summary: Protein-containing complex (IDA) from co-IP of NMHC-IIA with CXCR4 and myosin light chain. Reason: Protein-containing complex is uninformative; the specific complex MYH9 is part of is myosin II (heavy and light chains). Proposed replacements: myosin II complex Supporting Evidence: PMID:12421915 As expected, myosin L chain was also associated with CXCR4
GO:0042641 actomyosin	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Actomyosin (IDA). Reason: Full-length NM IIA filaments bind actin to form actomyosin. Supporting Evidence: PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP
GO:0042802 identical protein binding	IPI PMID:22483112 Asymmetric mode of Ca²⁺-S100A4 interaction with nonmuscle my...	KEEP AS NON CORE	Summary: Identical protein binding (IPI) in the S100A4/NMIIA NMR study. Reason: MYH9 heavy chains self-associate through the coiled-coil rod into dimers and bipolar filaments, so self-binding is real; however the term is weakly informative relative to myosin filament/complex terms. Supporting Evidence: PMID:22483112 Our NMR structure shows that an S100A4 dimer binds to a single myosin heavy chain in an asymmetrical configuration PMID:24072716 Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB
GO:0042802 identical protein binding	IPI PMID:31837246 High-throughput competitive fluorescence polarization assay ...	KEEP AS NON CORE	Summary: Identical protein binding (IPI) from the S100ome FP screen (NMIIA tail peptide). Reason: As above: self-association of the rod is real but weakly informative. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB
GO:0042803 protein homodimerization activity	IDA PMID:12237319 Mutations in human nonmuscle myosin IIA found in patients wi...	ACCEPT	Summary: Protein homodimerization activity (IDA): recombinant NM IIA HMM is a two-headed dimer. Reason: Heavy-chain dimerization via the coiled-coil is required for regulation and function of myosin II. Supporting Evidence: PMID:15065866 both heads of either thiophosphorylated or unphosphorylated heavy meromyosin bind very strongly to actin (K(d) < 10 nM) in the presence or absence of ADP
GO:0043495 protein-membrane adaptor activity	IMP PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	KEEP AS NON CORE	Summary: Protein-membrane adaptor activity (IMP): MyH9 links cell-surface nucleolin to the cytoskeleton. Reason: Reported by the authors as a physical linker role in endothelial cells; single study, context-specific, and not a general MYH9 activity. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0043531 ADP binding	IDA PMID:15065866 Two-headed binding of the unphosphorylated nonmuscle heavy m...	ACCEPT	Summary: ADP binding (IDA): NM IIA HMM heads bind ADP with ~1 microM affinity when bound to actin. Reason: Directly measured nucleotide-binding property of the motor cycle; part of the ATPase mechanism. Supporting Evidence: PMID:15065866 The heads have high and indistinguishable affinities for ADP (K(d) around 1 microM) when bound to actin
GO:0043534 blood vessel endothelial cell migration	IMP PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	KEEP AS NON CORE	Summary: Blood vessel endothelial cell migration (IMP) from MYH9 knockdown in the nucleolin angiogenesis study. Reason: Plausible consequence of myosin II-dependent motility in a specific cell type; non-core. Supporting Evidence: PMID:16403913 Knocking down endogenous MyH9, specifically inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts the organization of cell-surface nucleolin and inhibits its angiogenic function
GO:0045055 regulated exocytosis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Regulated exocytosis (electronic ortholog projection). Reason: Myosin II contributes to regulated exocytosis in several cell types (cortical actin clearance, lysosome exocytosis) as a supporting cytoskeletal motor. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Required for cortical actin clearance prior to oocyte exocytosis
GO:0045055 regulated exocytosis	IMP PMID:2732579 [Two sisters with pseudoidiopathic hypoparathyroidism presen...	KEEP AS NON CORE	Summary: Regulated exocytosis (IMP) - lysosome exocytosis requiring the Rab3a/Slp4-a/NMHC-IIA complex. Reason: Supported by the intended paper; context-specific. The cited PMID:2732579 is a wrong identifier (a 1989 Japanese case report on hypoparathyroidism); the WITH/FROM partner RAB3A and the annotation content identify the intended paper as PMID:27325790, whose number the cited id truncates. Evidence is taken from that paper. Supporting Evidence: PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis
GO:0045055 regulated exocytosis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Regulated exocytosis (ISS). Reason: As for the other regulated exocytosis rows. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Required for cortical actin clearance prior to oocyte exocytosis
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: Cadherin binding (HDA) from E-cadherin proximity-biotinylation proteomics. Reason: Proximity labeling near the E-cadherin tail does not demonstrate direct cadherin binding; actomyosin couples to cadherins through catenins and actin.
GO:0046718 symbiont entry into host cell	IDA PMID:20944748 Non-muscle myosin IIA is a functional entry receptor for her...	KEEP AS NON CORE	Summary: Symbiont entry into host cell (IDA): NMHC-IIA is an HSV-1 gB entry receptor. Reason: Well supported host-pathogen role; not a physiological function. Supporting Evidence: PMID:20944748 Here we show that non-muscle myosin heavy chain IIA (NMHC-IIA), a subunit of non-muscle myosin IIA (NM-IIA), functions as an HSV-1 entry receptor by interacting with gB
GO:0050900 leukocyte migration	NAS PMID:12421915 Cutting edge: association of the motor protein nonmuscle myo...	ACCEPT	Summary: Leukocyte migration (NAS). Reason: MyH9 is the only class II myosin in T cells and is required for T cell motility and uropod maintenance; rear actomyosin contraction in migrating leukocytes is a principal physiological use of the NMIIA motor. Supporting Evidence: PMID:15064761 MyH9 function is required for maintenance of the uropod and for T cell motility but is dispensable for synapse formation PMID:12421915 CXCR4 and motor protein nonmuscle myosin H chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin L chain
GO:0051015 actin filament binding	IBA GO_REF:0000033	ACCEPT	Summary: Actin filament binding (IBA). Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Supporting Evidence: PMID:15065866 both heads of either thiophosphorylated or unphosphorylated heavy meromyosin bind very strongly to actin (K(d) < 10 nM) in the presence or absence of ADP
GO:0051015 actin filament binding	IDA PMID:12237319 Mutations in human nonmuscle myosin IIA found in patients wi...	ACCEPT	Summary: Actin filament binding (IDA): NM IIA HMM moves actin filaments. Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Supporting Evidence: PMID:12237319 The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate
GO:0051015 actin filament binding	IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ...	ACCEPT	Summary: Actin filament binding (IDA) - actin selection of myosin in the menin study. Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Supporting Evidence: PMID:14508515 confirmed by glutathione-S-transferase pulldown assays, by coimmunoprecipitation, and by actin selection of myosin
GO:0051015 actin filament binding	IDA PMID:15845534 Disease-associated mutations and alternative splicing alter ...	ACCEPT	Summary: Actin filament binding (IDA) from the mutation enzymology study. Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Deferring to curator on II-A specific data. Supporting Evidence: PMID:15845534 R702C and N93K in human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C
GO:0051015 actin filament binding	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Actin filament binding (contributes_to) for full-length NM IIA with light chains. Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Supporting Evidence: PMID:24072716 Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP
GO:0051015 actin filament binding	IEA GO_REF:0000120	ACCEPT	Summary: Actin filament binding (electronic). Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking.
GO:0051015 actin filament binding	NAS PMID:16403913 The angiogenic function of nucleolin is mediated by vascular...	ACCEPT	Summary: Actin filament binding (NAS) - described as an actin-based motor protein. Reason: Actin filament binding is intrinsic to the myosin II motor head and to filament-mediated actin crosslinking. Supporting Evidence: PMID:16403913 Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin
GO:0060471 cortical granule exocytosis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cortical granule exocytosis (electronic ortholog projection from mouse oocytes). Reason: UniProt records (by similarity) a requirement for cortical actin clearance prior to oocyte exocytosis; an oocyte-specific role. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Required for cortical actin clearance prior to oocyte exocytosis
GO:0060471 cortical granule exocytosis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Cortical granule exocytosis (ISS). Reason: As above. Supporting Evidence: file:human/MYH9/MYH9-uniprot.txt Required for cortical actin clearance prior to oocyte exocytosis
GO:0060473 cortical granule	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Cortical granule (electronic). Reason: Oocyte-specific association with the cortical granule region; minor location.
GO:0060473 cortical granule	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Cortical granule (ISS). Reason: Oocyte-specific association; minor location.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: Extracellular exosome (HDA) from exosome proteomics. Reason: Detection in exosome proteomics reflects the abundance of NMIIA in the cell cortex; there is no evidence of a specific function in exosomes.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	MARK AS OVER ANNOTATED	Summary: Extracellular exosome (HDA) from exosome proteomics. Reason: Detection in exosome proteomics reflects the abundance of NMIIA in the cell cortex; there is no evidence of a specific function in exosomes.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	Summary: Extracellular exosome (HDA) from exosome proteomics. Reason: Detection in exosome proteomics reflects the abundance of NMIIA in the cell cortex; there is no evidence of a specific function in exosomes.
GO:0070062 extracellular exosome	HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells.	MARK AS OVER ANNOTATED	Summary: Extracellular exosome (HDA) from exosome proteomics. Reason: Detection in exosome proteomics reflects the abundance of NMIIA in the cell cortex; there is no evidence of a specific function in exosomes.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: Extracellular exosome (HDA) from exosome proteomics. Reason: Detection in exosome proteomics reflects the abundance of NMIIA in the cell cortex; there is no evidence of a specific function in exosomes.
GO:0070382 exocytic vesicle	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Exocytic vesicle (electronic ortholog projection). Reason: Myosin II acts on the cortical actin barrier around exocytic vesicles rather than being a vesicle component.
GO:0070382 exocytic vesicle	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Exocytic vesicle (ISS). Reason: As above.
GO:0072359 circulatory system development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Circulatory system development (ARBA electronic). Reason: Myosin IIA loss in mice affects embryonic and vascular development, but this broad developmental term is a downstream consequence of cytoskeletal function.
GO:0097513 myosin II filament	IDA PMID:24072716 Characterization of three full-length human nonmuscle myosin...	ACCEPT	Summary: Myosin II filament (IDA): full-length NM IIA forms bipolar filaments. Reason: Direct observation of bipolar filament assembly. Supporting Evidence: PMID:24072716 Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB
GO:0099500 vesicle fusion to plasma membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Vesicle fusion to plasma membrane (electronic ortholog projection). Reason: Myosin II contributes to exocytosis by remodelling cortical actin, not by participating in membrane fusion itself.
GO:0099500 vesicle fusion to plasma membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Vesicle fusion to plasma membrane (ISS). Reason: As above.
GO:0099512 supramolecular fiber	IEA GO_REF:0000117	ACCEPT	Summary: Supramolecular fiber (electronic). Reason: General parent of myosin filament and stress fiber; correct.
GO:1903919 negative regulation of actin filament severing	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Negative regulation of actin filament severing (electronic ortholog projection). Reason: In vitro, NMMIIA or its rod domain only minimally reduced gelsolin's actin-severing activity; the paper's main conclusion is that NMMIIA is needed to recruit gelsolin to collagen adhesions for phagocytosis. The negative regulation of severing is a minor biochemical observation rather than a demonstrated physiological role. Supporting Evidence: PMID:23325791 binding of NMMIIA to gelsolin minimally reduced the severing activity of gelsolin
GO:1903919 negative regulation of actin filament severing	IMP PMID:23325791 Collagen remodeling by phagocytosis is determined by collage...	MARK AS OVER ANNOTATED	Summary: Negative regulation of actin filament severing (IMP). Reason: In vitro, NMMIIA or its rod domain only minimally reduced gelsolin's actin-severing activity; the paper's main conclusion is that NMMIIA is needed to recruit gelsolin to collagen adhesions for phagocytosis. The negative regulation of severing is a minor biochemical observation rather than a demonstrated physiological role. Supporting Evidence: PMID:23325791 binding of NMMIIA to gelsolin minimally reduced the severing activity of gelsolin PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:1903919 negative regulation of actin filament severing	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of actin filament severing (ISS). Reason: In vitro, NMMIIA or its rod domain only minimally reduced gelsolin's actin-severing activity; the paper's main conclusion is that NMMIIA is needed to recruit gelsolin to collagen adhesions for phagocytosis. The negative regulation of severing is a minor biochemical observation rather than a demonstrated physiological role. Supporting Evidence: PMID:23325791 binding of NMMIIA to gelsolin minimally reduced the severing activity of gelsolin
GO:1903923 positive regulation of protein processing in phagocytic vesicle	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Positive regulation of protein processing in phagocytic vesicle (electronic ortholog projection). Reason: Derived from collagen phagocytosis studies in fibroblasts where NMMIIA knockdown blocks collagen uptake; the effect is on phagocytosis upstream of intracellular degradation, so a regulation of phagosomal protein processing term is an indirect over-interpretation. Supporting Evidence: PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:1903923 positive regulation of protein processing in phagocytic vesicle	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Positive regulation of protein processing in phagocytic vesicle (ISS). Reason: As above. Supporting Evidence: PMID:23325791 NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis
GO:1905684 regulation of plasma membrane repair	IMP PMID:2732579 [Two sisters with pseudoidiopathic hypoparathyroidism presen...	KEEP AS NON CORE	Summary: Regulation of plasma membrane repair (IMP). Reason: Silencing the Rab3a/Slp4-a/NMHC-IIA machinery collapses lysosomes perinuclearly and inhibits plasma membrane repair; context-specific role. The cited PMID:2732579 is a wrong identifier (a 1989 Japanese case report on hypoparathyroidism); the WITH/FROM partner RAB3A and the annotation content identify the intended paper as PMID:27325790, whose number the cited id truncates. Evidence is taken from that paper. Supporting Evidence: PMID:27325790 we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis PMID:27325790 Lysosome exocytosis plays a major role in resealing plasma membrane (PM) disruptions

Gene Description

Existing Annotations Review

Core Functions

Actin-activated ATP-driven motor: as the heavy chain of the non-muscle myosin IIA hexamer, MYH9 hydrolyses ATP to translocate and contract actin filaments, assembling into bipolar myosin II filaments in stress fibers, the cortex and the cytokinetic contractile ring.

Actin filament binding by the motor heads and by bipolar filaments, crosslinking actin into contractile actomyosin bundles.

Actomyosin contraction at the rear of migrating leukocytes: MYH9, the only class II myosin in T cells, is required for uropod maintenance and T cell motility, and in migrating immune cells NMIIA accumulates behind the nucleus where myosin II forces reposition it.

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