ACTA2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IBA GO_REF:0000033	UNDECIDED	Summary: PAINT-inferred extracellular activity remains unresolved beyond evidence of extracellular detection. Reason: The cached PTHR11937 PAINT record places GO:0005576 at PTN004322804, grounded in rat Acta2 evidence including an experimental basement-membrane descendant annotation. Its compartment interpretation remains unresolved. Human HDA independently supports extracellular occurrence, but the present IBA qualifier is is_active_in, which additionally asserts molecular activity there. Neither the accessible donor material nor the human detection record resolves that activity. Retain uncertainty without changing the source qualifier or treating the PAINT assertion as disproved by ACTA2 lacking a signal peptide. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN004322804 UNRESOLVED Cached PTN IBD and rat descendant annotation inspected. Human HDA corroborates extracellular detection but does not settle the is_active_in claim; donor compartment/activity evidence remains unresolved. The target location row is not used as proof that the phylogenetic inference is circular.
GO:0015629 actin cytoskeleton	IBA GO_REF:0000033	ACCEPT	Summary: ACTA2 is a structural component of the actin cytoskeleton. Reason: PAINT places this conserved location at PTN002631484. Human ACTA2 forms filaments in biochemical assays, and rat Acta2 localizes to contractile actin arrays in stellate cells. These data support inheritance of the cytoskeletal location; there is no target-specific loss of polymer-forming capacity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002631484 SUPPORTS TRANSFER The cached IBD supports inherited actin-cytoskeleton localization. Human filament biochemistry corroborates the target assignment; extant donor counts are not used as a confidence score. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0005200 structural constituent of cytoskeleton	IBA GO_REF:0000033	ACCEPT	Summary: ACTA2 supplies the actin polymer that supports cell structure and contractile force transmission. Reason: The structural role assigned at PAINT node PTN000940351 is supported directly by human wild-type ACTA2 filament assays and by the effects of Acta2 depletion on contractile arrays. Actin polymerization and incorporation into the force-bearing apparatus support this molecular function without requiring a claim about a particular myosin motor activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000940351 SUPPORTS TRANSFER Inspected the cached IBD for structural constituent of cytoskeleton. Human ACTA2 filament formation independently supports the inherited structural function. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt cytoskeleton location describes a core site of ACTA2 action. Reason: The UniProt subcellular-location mapping to cytoskeleton is correct at its stated resolution. ACTA2 contributes contractile filaments and dynamic cytoskeletal arrays; a broad but valid location remains core even when more specific locations are also available. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0090 SUPPORTS TRANSFER The cached UniProt record explicitly states Cytoplasm, cytoskeleton. The mapped location is independently consistent with human ACTA2 filament studies. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0007010 cytoskeleton organization	IEA GO_REF:0000108	ACCEPT	Summary: ACTA2 polymerization contributes directly to cytoskeleton organization. Reason: The GO_REF:0000108 mapping derives the process from the structural-constituent activity. ACTA2 performs the structural work through filament assembly and turnover, rather than merely marking cells that contain a cytoskeleton. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0005200 SUPPORTS TRANSFER The source molecular-function annotation is supported by ACTA2 filament biochemistry; the inferred structural contribution to cytoskeleton organization is appropriate. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding from the BioPlex 2.0 interaction with SCGB1A1 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with SCGB1A1. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding from the BioPlex 2.0 interaction with GM2A is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with GM2A. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding from the BioPlex 2.0 interaction with TCP11L2 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with TCP11L2. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding from the BioPlex 2.0 interaction with YIPF2 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with YIPF2. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding from the BioPlex 2.0 interaction with MAP1LC3C is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with MAP1LC3C. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from the BioPlex 3.0 interaction with SCGB1A1 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with SCGB1A1. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from the BioPlex 3.0 interaction with GM2A is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with GM2A. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from the BioPlex 3.0 interaction with TCP11L2 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with TCP11L2. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from the BioPlex 3.0 interaction with YIPF2 is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with YIPF2. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding from the BioPlex 3.0 interaction with MAP1LC3C is functionally uninformative. Reason: The source annotation and cached UniProt interaction record associate ACTA2 with MAP1LC3C. Affinity-purification recovery supports an association under the assay conditions, but does not establish a specific catalytic, adaptor, receptor, or regulatory function for ACTA2 in that pair. Remove the generic molecular-function annotation under the protein-binding policy. This decision does not deny the reported interaction or infer an impossible encounter from the partners' usual compartments. The exact pair-level proteomic record was not independently re-extracted.
GO:0001725 stress fiber	IEA GO_REF:0000107	ACCEPT	Summary: Rat Acta2 stress-fiber localization supports the conserved human contractile-array location. Reason: PMID:24204762 shows Acta2 in stress fibers of cultured rat hepatic stellate cells and tests the contribution of these arrays to motility and contraction. Together with human ACTA2 filament biochemistry, this supports a core cytoskeletal location; cell-specific regulation of expression does not alter the structural assignment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER Rat Acta2 carries IDA stress-fiber evidence from PMID:24204762. The structural localization is consistent with the human ortholog. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; Rat Acta2 carries IDA stress-fiber evidence from PMID:24204762. The structural localization is consistent with the human ortholog. Supporting Evidence: PMID:24204762 Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction.
GO:0005604 basement membrane	IEA GO_REF:0000107	UNDECIDED	Summary: The rat testis study does not resolve extracellular basement membrane versus closely apposed Acta2-positive cells sufficiently for a confident human transfer. Reason: The donor IDA is PMID:30476341. Its externally accessible Results describe staining around seminiferous-cord basement membranes and Acta2-expressing cells presumed to be peritubular myoid cells; its figure caption also describes basement-membrane deposition. These descriptions leave the cellular-versus-extracellular interpretation unresolved at the reported imaging resolution. The local cache lacks the full Results. Preserve uncertainty about this specific compartment without asserting that the rat curator confused cell adjacency with matrix incorporation. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P62738 UNRESOLVED The donor IDA is genuine, but the exact cellular versus extracellular interpretation of PMID:30476341 remains unresolved after examining accessible primary Results and figure descriptions. ensembl:ENSRNOP00000073101 UNRESOLVED Alternative database identifier for the same experimentally annotated donor; The donor IDA is genuine, but the exact cellular versus extracellular interpretation of PMID:30476341 remains unresolved after examining accessible primary Results and figure descriptions.
GO:0006936 muscle contraction	IEA GO_REF:0000107	MODIFY	Summary: The contractile contribution is best represented as smooth muscle contraction. Reason: Human wild-type ACTA2 filaments interact with smooth muscle myosin in the reconstituted assay of PMID:26153420, and ACTA2 disease and correction studies support a contractile role in smooth muscle cells. ACTA2 supplies the force-bearing actin polymer in this process. Replace the generic muscle-contraction term with GO:0006939. The rat donor annotation traces to PMID:11953441, whose accessible abstract concerns promoter regulation in osteoblasts; that source does not independently resolve the contractile assay, so the refinement rests on the human evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P62738 UNRESOLVED The rat donor and its PMID:11953441 provenance are resolved, but the primary contractile assay is not available in the abstract. Human ACTA2/myosin experiments independently justify the more specific process. ensembl:ENSRNOP00000073101 UNRESOLVED Alternative database identifier for the same experimentally annotated donor; The rat donor and its PMID:11953441 provenance are resolved, but the primary contractile assay is not available in the abstract. Human ACTA2/myosin experiments independently justify the more specific process. Proposed replacements: smooth muscle contraction Supporting Evidence: PMID:26153420 In an in vitro motility assay, smooth muscle myosin moves R258C filaments more slowly than WT, and the slowing is exacerbated by smooth muscle tropomyosin.
GO:0015629 actin cytoskeleton	IEA GO_REF:0000107	ACCEPT	Summary: Ortholog transfer of actin-cytoskeleton localization agrees with the human structural function. Reason: The rat donor carries experimental cytoskeletal localization, including stress-fiber evidence from PMID:24204762. Human ACTA2 polymerizes into filaments and participates in smooth-muscle contractile and subcortical actin arrays, supporting the broader cytoskeletal location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER The traced rat record contains experimental actin-cytoskeleton and stress-fiber annotations. Human filament evidence corroborates transfer. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; The traced rat record contains experimental actin-cytoskeleton and stress-fiber annotations. Human filament evidence corroborates transfer. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0019901 protein kinase binding	IEA GO_REF:0000107	UNDECIDED	Summary: The mouse Acta2–LRRK2 binding source requires isoform-level primary verification. Reason: The donor is mouse Acta2 P62737, with an IPI annotation from PMID:21307259 and LRRK2 as the recorded kinase partner. The accessible abstract describes synaptic-vesicle trafficking and LRRK2 interactions but does not identify the Acta2-specific assay. The full interaction table could not be inspected. Preserve uncertainty about the specific binding assertion; the neuronal context alone is not evidence of a wrong-actin assignment. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P62737 UNRESOLVED The historical donor record resolves mouse Acta2 and LRRK2, but the exact primary isoform-specific experiment in PMID:21307259 remains inaccessible. ensembl:ENSMUSP00000048218 UNRESOLVED Alternative database identifier for the same experimentally annotated donor; The historical donor record resolves mouse Acta2 and LRRK2, but the exact primary isoform-specific experiment in PMID:21307259 remains inaccessible.
GO:0061870 positive regulation of hepatic stellate cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acta2 promotes migration in the tested hepatic stellate-cell context. Reason: PMID:24204762 uses several Acta2 perturbations and scratch-wound and transmembrane migration assays. Reduced Acta2 lowers the phenotype without lowering the cytoplasmic actin isoforms measured. ACTA2 provides contractile cytoskeletal structure needed for this cellular behavior. Retain the ortholog transfer as a context-dependent process, while leaving the degree of isoform substitution in human stellate cells unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER Rat Acta2 IMP from PMID:24204762 supports the stellate-cell migration phenotype. This context is retained as non-core, without claiming exclusivity to this actin isoform. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; Rat Acta2 IMP from PMID:24204762 supports the stellate-cell migration phenotype. This context is retained as non-core, without claiming exclusivity to this actin isoform. Supporting Evidence: PMID:24204762 Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction.
GO:0061874 positive regulation of hepatic stellate cell contraction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acta2 promotes contraction in the tested hepatic stellate-cell context. Reason: PMID:24204762 uses several Acta2 perturbations and collagen-lattice contraction assays. Reduced Acta2 lowers the phenotype without lowering the cytoplasmic actin isoforms measured. ACTA2 provides contractile cytoskeletal structure needed for this cellular behavior. Retain the ortholog transfer as a context-dependent process, while leaving the degree of isoform substitution in human stellate cells unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER Rat Acta2 IMP from PMID:24204762 supports the stellate-cell contraction phenotype. This context is retained as non-core, without claiming exclusivity to this actin isoform. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; Rat Acta2 IMP from PMID:24204762 supports the stellate-cell contraction phenotype. This context is retained as non-core, without claiming exclusivity to this actin isoform. Supporting Evidence: PMID:24204762 Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction.
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acta2 depletion lowers ERK1/2 activation in cultured hepatic stellate cells. Reason: Figure 7 of PMID:24204762 tests Acta2 siRNA in rat stellate cells and reports reduced ERK1/2 phosphorylation with unchanged beta-actin and tubulin controls. This supports positive regulation in that cellular context even though ACTA2 is not itself an ERK kinase. The precise cytoskeleton-to-signaling mechanism remains unresolved; a direct biochemical activation mechanism is not asserted. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER The donor IMP is supported by the Acta2-specific siRNA and ERK-phosphorylation experiment in PMID:24204762; retain a contextual signaling effect, not intrinsic kinase activity. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; The donor IMP is supported by the Acta2-specific siRNA and ERK-phosphorylation experiment in PMID:24204762; retain a contextual signaling effect, not intrinsic kinase activity. Supporting Evidence: PMID:24204762 These data suggested that Acta2 regulates Erk activity during stellate cell activation.
GO:0071560 cellular response to transforming growth factor beta stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acta2 expression responds to TGF-beta in the tested fibroblast context. Reason: The rat donor IEP traces to PMID:17043753, whose abstract explicitly reports TGF-beta-induced alpha-smooth-muscle actin expression in NRK-49F fibroblasts and its suppression by prohibitin overexpression. A cellular response can include altered gene expression; this annotation does not require ACTA2 to be the TGF-beta receptor or a direct signal-transduction enzyme. Retain the context-dependent response. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER The donor IEP source explicitly supports TGF-beta-responsive alpha-SMA expression. The source does not establish a direct receptor or kinase role. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; The donor IEP source explicitly supports TGF-beta-responsive alpha-SMA expression. The source does not establish a direct receptor or kinase role.
GO:0072051 juxtaglomerular apparatus development	IEA GO_REF:0000107	UNDECIDED	Summary: The developmental role cannot be established from the accessible differentiation-marker evidence. Reason: PMID:30645697 describes differentiation of rat amniotic-fluid-derived stem cells into renal-like cells and alpha-SMA/renin expression in a juxtaglomerular-like population. The abstract supports marker expression, but the full experiment needed to assess ACTA2 participation in apparatus development was unavailable. Retain uncertainty about the donor IEP process and its human transfer rather than asserting that all such evidence is invalid. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P62738 UNRESOLVED The donor IEP and study identity are resolved; the available abstract does not resolve developmental participation beyond marker expression. ensembl:ENSRNOP00000073101 UNRESOLVED Alternative database identifier for the same experimentally annotated donor; The donor IEP and study identity are resolved; the available abstract does not resolve developmental participation beyond marker expression.
GO:2000491 positive regulation of hepatic stellate cell activation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acta2 contributes to the contractile phenotype acquired during hepatic stellate-cell activation. Reason: PMID:24204762 introduces antisense during culture activation of freshly isolated rat stellate cells and evaluates activation-associated motility and contraction. The perturbations were not confined to an already activated endpoint. Retain the process at this context-dependent scope, without treating ACTA2 as a universal master regulator of all activation programs. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62738 SUPPORTS TRANSFER The donor IMP comes from interventions during culture activation in PMID:24204762. The structural/contractile activation phenotype supports the contextual transfer. ensembl:ENSRNOP00000073101 SUPPORTS TRANSFER Alternative database identifier for the same experimentally annotated donor; The donor IMP comes from interventions during culture activation in PMID:24204762. The structural/contractile activation phenotype supports the contextual transfer. Supporting Evidence: PMID:24204762 Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction.
GO:0005829 cytosol	TAS Reactome:R-HSA-445699	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models myosin ATP hydrolysis in the actomyosin cycle and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-445700	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models ATP binding to myosin and release of the actomyosin cross-bridge and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-445704	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models calcium/caldesmon regulation of access to actin and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-445705	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models myosin ADP release and the actomyosin power stroke and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-9604664	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models NOTCH-dependent expression of ACTA2 and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-9914537	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models the cytoskeletal side of the dystrophin-associated complex and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-9934294	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models cadherin–catenin/vinculin coupling to F-actin and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-9934410	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models cadherin adhesion in an actin-associated membrane environment and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-9934486	ACCEPT	Summary: Cytosol is a core compartment for ACTA2 monomers and contractile actin assemblies. Reason: The cached Reactome event models alpha-catenin recruitment of F-actin and assigns the ACTA2-containing entity to cytosol. This location agrees with its core intracellular structural function. The event supplies compartment evidence, not proof that ACTA2 performs every catalytic or regulatory step shown in the reaction.
GO:0016887 ATP hydrolysis activity	ISS GO_REF:0000024	ACCEPT	Summary: ACTA2 retains the intrinsic ATP-hydrolysis activity of conventional actins. Reason: The ISS donor is pig skeletal actin ACTA1 P68137. The cached UniProt ACTA2 catalytic-activity statement records ATP hydrolysis with this same similarity source, and the existing sequence/structure comparison supports conservation of the nucleotide cleft. Accept the biochemical inference while keeping isoform-specific kinetic measurements distinct from the actin-activated myosin ATPase assays in other papers. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P68137 SUPPORTS TRANSFER Pig ACTA1 is the explicit similarity source in the cached UniProt catalytic-activity block. Historical QuickGO retrieval records donor EXP; the original donor assay was not independently re-extracted, and no human ACTA2-specific turnover rate is asserted. Supporting Evidence: file:human/ACTA2/ACTA2-uniprot.txt Reaction=ATP + H2O = ADP + phosphate + H(+);
GO:0032991 protein-containing complex	IDA PMID:18468998 Blood pressure is regulated by an alpha1D-adrenergic recepto...	KEEP AS NON CORE	Summary: ACTA2 was recovered with the alpha1D-adrenergic-receptor purification in HEK293 cells. Reason: PMID:18468998 Table 3 lists aortic smooth-muscle actin in the TAP-alpha1D-adrenergic-receptor preparation with one distinct peptide and 4% coverage. This is positive complex-association evidence at the purification resolution. Follow-up functional tests center on dystrophin/syntrophin components and do not establish an ACTA2-specific receptor-regulatory mechanism. Retain the broad complex location as non-core; low coverage is a scope limitation, not proof that the association is false.
GO:0005737 cytoplasm	IDA PMID:11927518 Endothelial cell senescence in human atherosclerosis: role o...	ACCEPT	Summary: The broad cytoplasmic localization is consistent with ACTA2 core biology. Reason: The source IDA derives from PMID:11927518, a study of endothelial-cell senescence. The accessible abstract does not expose the complete ACTA2 localization experiment, so no particular counterstain, subcellular subdomain, or isoform-discrimination method is inferred. The annotated broad cytoplasm location is independently supported by the UniProt record and ACTA2 filament biology, and is retained with deference to the primary curator at this resolution. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0010628 positive regulation of gene expression	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken donor gene-expression regulation experiment remains unresolved. Reason: The donor annotation traces to PMID:10633868, which examines alpha-SMA during chick endothelial-to-mesenchymal transformation. Its abstract supports localization to motile appendages and an antisense migration phenotype, but does not identify the experiment supporting positive regulation of gene expression. Full text was unavailable. Structural actins can affect gene regulation; neither protein class nor reuse of the paper for other terms disproves this particular annotation. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 UNRESOLVED The chicken ACTA2 IDA provenance is resolved, but the specific positive gene-expression regulation experiment is not visible in the accessible abstract.
GO:0030027 lamellipodium	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Chicken alpha-SMA is observed in lamellipodium structures during mesenchymal transformation. Reason: The PMID:10633868 abstract explicitly reports alpha-SMA in lamellipodia and filopodia of invading mesenchymal cells. The conserved actin structural role supports transfer of this context-dependent location to human ACTA2. The full image-level isoform controls were unavailable, so retain the reported location without asserting that ACTA2 is the predominant actin in every such protrusion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08023 SUPPORTS TRANSFER The donor IDA localization is explicitly described in the primary abstract of PMID:10633868. Transfer is retained at the developmental cell-context scope.
GO:0030175 filopodium	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Chicken alpha-SMA is observed in filopodium structures during mesenchymal transformation. Reason: The PMID:10633868 abstract explicitly reports alpha-SMA in lamellipodia and filopodia of invading mesenchymal cells. The conserved actin structural role supports transfer of this context-dependent location to human ACTA2. The full image-level isoform controls were unavailable, so retain the reported location without asserting that ACTA2 is the predominant actin in every such protrusion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08023 SUPPORTS TRANSFER The donor IDA localization is explicitly described in the primary abstract of PMID:10633868. Transfer is retained at the developmental cell-context scope.
GO:0044297 cell body	ISS GO_REF:0000024	UNDECIDED	Summary: The cell-body localization requires inspection of the chicken donor images or results. Reason: GO:0044297 describes the body of a projection-bearing cell and is not restricted to neurons. The chicken donor IDA traces to PMID:10633868. Its abstract describes alpha-SMA in appendages and invading mesenchymal cells, but does not resolve the separately annotated cell-body pattern. Keep this specific localization uncertain until the full source is accessible; the term is not rejected on an incorrect neuronal restriction. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 UNRESOLVED The source IDA is resolved, but the exact cell-body localization is not established by the accessible abstract.
GO:0090131 mesenchyme migration	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Alpha-SMA contributes to mesenchymal-cell movement in the chick cardiac-explant model. Reason: PMID:10633868 reports that antisense suppression of alpha-SMA impairs formation of motile appendages and mesenchymal-cell accumulation in atrioventricular explant cultures. ACTA2 supplies cytoskeletal structure for cell movement. Retain the conserved structural contribution as a developmental non-core process, without converting the experiment into a general transcriptional-regulator claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08023 SUPPORTS TRANSFER The donor IMP migration phenotype is explicit in the primary abstract. Human transfer is retained as a context-dependent structural role.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: ACTA2 detection in an extracellular-vesicle proteomic preparation is retained as a non-core location. Reason: PMID:23533145 characterizes extracellular vesicles from expressed prostatic secretions. The HDA annotation is a detection-level location statement; it does not establish a secretory route or a physiological extracellular actin mechanism. The exact ACTA2 peptide assignment was not independently re-extracted, and no contamination explanation is inferred solely from the intracellular core function.
GO:0019901 protein kinase binding	ISS GO_REF:0000024	UNDECIDED	Summary: The mouse Acta2–LRRK2 binding source requires isoform-level primary verification. Reason: The donor is mouse Acta2 P62737, with an IPI annotation from PMID:21307259 and LRRK2 as the recorded kinase partner. The accessible abstract describes synaptic-vesicle trafficking and LRRK2 interactions but does not identify the Acta2-specific assay. The full interaction table could not be inspected. Preserve uncertainty about the specific binding assertion; the neuronal context alone is not evidence of a wrong-actin assignment. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P62737 UNRESOLVED The historical donor record resolves mouse Acta2 and LRRK2, but the exact primary isoform-specific experiment in PMID:21307259 remains inaccessible.
GO:0005576 extracellular region	HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter...	KEEP AS NON CORE	Summary: The extracellular proteomic detection supports a non-core extracellular pool. Reason: PMID:23580065 is the cited high-throughput extracellular protein study. Retain the curator-assigned detection at the broad extracellular-region resolution, without claiming an extracellular contractile function or inferring contamination from ACTA2 lacking a conventional secretion signal. The local record is abstract-only and the exact peptide list was not independently re-extracted.
GO:0005737 cytoplasm	IDA PMID:17464107 Development of glomerular endothelial cells, podocytes and m...	ACCEPT	Summary: The broad cytoplasmic localization is consistent with ACTA2 core biology. Reason: The source IDA derives from PMID:17464107, a study of human fetal and infant renal development. The accessible abstract does not expose the complete ACTA2 localization experiment, so no particular counterstain, subcellular subdomain, or isoform-discrimination method is inferred. The annotated broad cytoplasm location is independently supported by the UniProt record and ACTA2 filament biology, and is retained with deference to the primary curator at this resolution. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0072144 glomerular mesangial cell development	IEP PMID:17464107 Development of glomerular endothelial cells, podocytes and m...	UNDECIDED	Summary: The mesangial-development process requires evidence beyond the accessible alpha-SMA marker description. Reason: The human fetal/infant kidney study explicitly uses alpha-smooth muscle actin as a marker for mesangial cells and reports stage-dependent staining. This descriptive assay establishes expression, not that ACTA2 performs a step of mesangial development. The full primary Results were inaccessible, so possible additional evidence behind the curator's IEP assertion remains unresolved. Keep UNDECIDED rather than asserting that the full study contains only the marker assay. Supporting Evidence: PMID:17464107 muscle actin (alpha-SMA), a marker for mesangial cells
GO:0005737 cytoplasm	IDA PMID:12355421 Cellular localization of cyclooxygenase-1 and cyclooxygenase...	ACCEPT	Summary: The broad cytoplasmic localization is consistent with ACTA2 core biology. Reason: The source IDA derives from PMID:12355421, a study of retinal immunohistochemistry. The accessible abstract does not expose the complete ACTA2 localization experiment, so no particular counterstain, subcellular subdomain, or isoform-discrimination method is inferred. The annotated broad cytoplasm location is independently supported by the UniProt record and ACTA2 filament biology, and is retained with deference to the primary curator at this resolution. Supporting Evidence: PMID:26153420 Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region.
GO:0009615 response to virus	IEP PMID:16548883 Transcriptomic and proteomic analyses of rhabdomyosarcoma ce...	KEEP AS NON CORE	Summary: ACTA2 expression changes in response to enterovirus 71 in the studied human cell context. Reason: PMID:16548883 studies EV71 infection of human rhabdomyosarcoma cells. The cached UniProt induction statement explicitly records ACTA2 upregulation with experimental evidence from this paper. GO:0009615 includes changes in gene expression resulting from a viral stimulus; it does not assert antiviral effector activity. Retain this contextual response without assigning an immune molecular function. Supporting Evidence: file:human/ACTA2/ACTA2-uniprot.txt Up-regulated in response to enterovirus 71 (EV71) infection.
GO:0017022 myosin binding	IDA PMID:26153420 Vascular disease-causing mutation R258C in ACTA2 disrupts ac...	NEW	Summary: Human ACTA2 filaments engage smooth-muscle myosin in a reconstituted motility assay. Reason: PMID:26153420 directly compares purified human wild-type and R258C ACTA2 filaments in smooth-muscle myosin motility and load-dependent assays. The externally inspected Methods/SI specify recombinant human smooth-muscle myosin MYH11 with light chains. The wild-type experiments support myosin binding independently of any comparative annotation gap or presumed PAINT-node defect. Retain the specific molecular function; it does not imply that every ACTA2 disease phenotype arises solely from altered myosin binding. As a same-role comparator, the cached human ACTA1 GOA carries myosin binding by TAS. This supports the appropriateness of the MF for an actin filament partner; the ACTA2 proposal is grounded in its own assay. Supporting Evidence: PMID:26153420 In an in vitro motility assay, smooth muscle myosin moves R258C filaments more slowly than WT, and the slowing is exacerbated by smooth muscle tropomyosin.
GO:0005524 ATP binding	ISS GO_REF:0000024	NEW	Summary: The conserved conventional-actin nucleotide pocket supports ATP binding by ACTA2. Reason: The cached UniProt record classifies ACTA2 as ATP-binding, and the existing structural comparison supports preservation of the conventional-actin nucleotide pocket. The retained ISS proposal uses human cardiac actin ACTC1 P68032, whose historical donor record carries ATP-binding IDA from PMID:16611632. The accessible abstract does not expose that binding assay, so the original donor experiment is not claimed to have been re-read. This is a similarity inference supported by the ACTA2 sequence and curated biochemical record, not a measured human ACTA2 affinity. No conclusion about retirement of a keyword pipeline follows from an empty annotation query. Comparator inspection found ATP binding on human ACTA1 (TAS) and ACTB (IEA from UniProtKB-KW:KW-0067) in their cached GOA. ACTA2 carries the ATP-binding keyword too. This supports the molecular-function inference but does not establish why ACTA2 lacks that particular electronic row. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P68032 SOURCE WEAK OR INFERRED Human ACTC1 is a paralog with historical ATP-binding IDA provenance. The precise donor experiment remains uninspected; independent ACTA2 nucleotide-pocket conservation and UniProt biochemical annotation support the similarity inference. Supporting Evidence: file:human/ACTA2/ACTA2-uniprot.txt Acetylation; Aortic aneurysm; ATP-binding; Cytoplasm; Cytoskeleton;

Gene Description

Existing Annotations Review

Core Functions

Hydrolyzes ATP through the conserved conventional-actin nucleotide pocket, supporting the nucleotide-dependent assembly and turnover of cytoskeletal filaments. The conserved biochemical machinery supports transfer of this intrinsic actin activity from pig skeletal actin to human ACTA2.

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