ACTA1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0015629 actin cytoskeleton	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred actin-cytoskeleton localization agrees with direct human muscle evidence. Reason: The cached PTHR11937 PAINT record places the actin-cytoskeleton IBD at PTN002631484. ACTA1 inherits that ancestral assertion and has direct evidence from insoluble actin filaments in patient muscle (PMID:15198992). Its appearance among the descendant experimental sources is expected and does not make the inference circular. The conserved filament-forming role supports the location; donor count is not the basis of acceptance. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002631484 · PTN002631484 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0015629, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Conserved ACTA1 filament structure and muscle evidence support retention in the target. Supporting Evidence: PMID:15198992 present within insoluble actin filaments isolated from muscle from two ACTA1 NM
GO:0005200 structural constituent of cytoskeleton	IBA GO_REF:0000033	ACCEPT	Summary: The ancestral structural-function assertion is consistent with ACTA1 being a thin-filament protomer. Reason: GO:0005200 describes contribution to cytoskeletal structural integrity. The cached PTHR11937 PAINT file records this IBD at PTN000940351, with explicit IRD losses in some descendant branches. ACTA1 retains the assertion, and its filament-forming role and human myopathy evidence independently support it. This is an ancestral-node judgment, not a vote among extant donors; the presence of actin-related proteins among the sources does not invalidate the placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000940351 · PTN000940351 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0005200, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Conserved ACTA1 filament structure and muscle evidence support retention in the target. Supporting Evidence: PMID:10508519 Muscle contraction results from the force generated between the thin filament
GO:0001725 stress fiber	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: The inherited stress-fiber annotation has direct target evidence in transfected myoblasts. Reason: The full original PMID:15198992 was recovered from the University of Geneva archive (DOI:10.1093/hmg/ddh185). Results on journal page 1733 and Figure 5A show wild-type ACTA1-EGFP in stress fibers in C2C12 myoblasts; differentiated cells also show sarcomeric incorporation in Figure 5B(viii). This supports a real culture-context localization, retained as non-core relative to the mature muscle thin filament. Local publication cache remains abstract-only; the full-paper route and figure are documented in notes. PAINT places this assertion at PTN000233075 using human ACTA1 experimental evidence; the self-source is legitimate. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000233075 · PTN000233075 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0001725, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Retain the inherited stress-fiber location as a supported culture context (PMID:15198992 Figure5A). Supporting Evidence: PMID:15198992
GO:0005865 striated muscle thin filament	IBA GO_REF:0000033	ACCEPT	Summary: PAINT supports ACTA1 striated muscle thin filament. Reason: The cached PAINT IBD at PTN000233075 is grounded in experimental evidence on human ACTA1. The target appearing among those descendant sources is expected. Human ACTA1 polymerization and muscle thin-filament abnormalities support this retained ancestral function; there is no evidence of a target-specific loss. For assembly, ACTA1 supplies the polymerizing structural subunit itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000233075 · PTN000233075 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0005865, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Conserved ACTA1 filament structure and muscle evidence support retention in the target. Supporting Evidence: PMID:15198992 present within insoluble actin filaments isolated from muscle from two ACTA1 NM
GO:0005884 actin filament	IBA GO_REF:0000033	ACCEPT	Summary: PAINT supports ACTA1 actin filament. Reason: The cached PAINT IBD at PTN000233075 is grounded in experimental evidence on human ACTA1. The target appearing among those descendant sources is expected. Human ACTA1 polymerization and muscle thin-filament abnormalities support this retained ancestral function; there is no evidence of a target-specific loss. For assembly, ACTA1 supplies the polymerizing structural subunit itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000233075 · PTN000233075 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0005884, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Conserved ACTA1 filament structure and muscle evidence support retention in the target. Supporting Evidence: PMID:12849983 cycles of polymerisation and depolymerisation
GO:0030240 skeletal muscle thin filament assembly	IBA GO_REF:0000033	ACCEPT	Summary: PAINT supports ACTA1 skeletal muscle thin filament assembly. Reason: The cached PAINT IBD at PTN000233075 is grounded in experimental evidence on human ACTA1. The target appearing among those descendant sources is expected. Human ACTA1 polymerization and muscle thin-filament abnormalities support this retained ancestral function; there is no evidence of a target-specific loss. For assembly, ACTA1 supplies the polymerizing structural subunit itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000233075 · PTN000233075 SUPPORTS TRANSFER PAINT ancestral IBD for GO:0030240, verified in cached PTHR11937-paint.tsv. Target experimental evidence can legitimately seed this node; ACTA1 self-inclusion is not circular. Conserved ACTA1 filament structure and muscle evidence support retention in the target. Supporting Evidence: PMID:11333380 "whorling" of actin thin filaments
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: UniProt location mapping places the filament-forming protein in the cytoskeleton. Reason: The broad cytoskeleton location is correct for a structural actin subunit. Preserve the resolution of the UniProt subcellular-location mapping; the presence of more specific thin-filament and actin-cytoskeleton annotations does not make this source assertion non-core. The core summary records the more informative muscle location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0090 · UniProt controlled-vocabulary term (not a gene product) SUPPORTS TRANSFER UniProt location vocabulary supports the cytoskeleton mapping at its stated resolution. Supporting Evidence: file:human/ACTA1/ACTA1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: BioPlex reports an ACTA1-ANXA8 physical association; the generic binding term adds no functional mechanism. Reason: The seeded IPI record identifies UniProtKB:P13928 (ANXA8), consistent with the UniProt interaction record and the BioPlex affinity-purification interaction source PMID:28514442. Remove GO:0005515 as uninformative under the generic-binding policy, without rejecting the physical association. A different cell line, a high-throughput method or possible actin carry-over is not proof of a false interaction. No specific regulatory or catalytic molecular function follows from this pair. Supporting Evidence: PMID:28514442 affinity purification-mass spectrometry
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with ZNF20 does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with INCA1 does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with ASCL4 does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with LIAT1 isoform 4 does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with PNMA5 does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with SYNC does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The curated interaction with CAMK2A does not specify an informative ACTA1 molecular function. Reason: PMID:32814053 reports systematic yeast two-hybrid mapping. The original full paper recovered from the MDC repository describes four independent screens, pairwise retesting and DULIP validation of a subset. Accept the curated pair as reported physical-interaction evidence; remove only the generic GO:0005515 functional annotation. The study does not establish a particular ACTA1 activity for this pair, and no such activity is inferred from the partner name or tissue. Pair-specific DULIP validation has not been established here. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: BioPlex reports an ACTA1-ANXA8 physical association; the generic binding term adds no functional mechanism. Reason: The seeded IPI record identifies UniProtKB:P13928 (ANXA8), consistent with the UniProt interaction record and the BioPlex affinity-purification interaction source PMID:33961781. Remove GO:0005515 as uninformative under the generic-binding policy, without rejecting the physical association. A different cell line, a high-throughput method or possible actin carry-over is not proof of a false interaction. No specific regulatory or catalytic molecular function follows from this pair. Supporting Evidence: PMID:33961781 affinity-purification mass spectrometry
GO:0005515 protein binding	IPI PMID:18835984 Interaction of the mycobacterial heparin-binding hemagglutin...	REMOVE	Summary: HBHA binding to muscle actin is reported, but the generic binding term adds no informative ACTA1 function. Reason: The original full text at PMC2583614, Methods, preparation of actin-modified surfaces, specifies actin from bovine muscle. It supports HBHA binding to muscle actin; direct attribution of this assay to human ACTA1 remains unresolved. Remove only the uninformative GO:0005515 assertion under the generic-binding policy, without rejecting the interaction or claiming a demonstrated human-specific assay. No more specific ACTA1 molecular function is established by this source, and no host-pathogen or inhibitory activity is inferred. The local PMID:18835984 cache remains abstract-only, with external full-text provenance documented in notes. Supporting Evidence: PMID:18835984 HBHA is able to specifically bind actin, via both its N-terminal and C-terminal
GO:0048741 skeletal muscle fiber development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Mouse Acta1 developmental expression supports a muscle-development context. Reason: The source is the mouse skeletal-actin ortholog P68134, with PMID:2731651 as the donor publication. Its accessible abstract examines developmental actin expression and altered alpha-actin expression in BALB/c mice. Retain the established ortholog annotation as developmental context; do not reinterpret that study as a targeted Acta1 knockout or as direct proof of a differentiation-regulatory mechanism. ACTA1 structural assembly and contraction remain the core roles. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P68134 · Acta1 (Mus musculus, Swiss-Prot) SUPPORTS TRANSFER Mouse skeletal-actin ortholog with developmental-expression source PMID:2731651; retain developmental context without asserting a targeted Acta1 knockout. ensembl:ENSMUSP00000034453 · Ensembl protein identifier UNRESOLVED Ensembl protein identifier in the source Compara assertion; its exact cross-reference was not independently recovered. The separately identified mouse Acta1 P68134 source supports the developmental context. Supporting Evidence: PMID:2731651 examined the expression of this actin gene pair throughout the development of skeletal and cardiac muscle in BALB/c mice.
GO:0048741 skeletal muscle fiber development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Mouse Acta1 developmental expression supports a muscle-development context. Reason: The source is the mouse skeletal-actin ortholog P68134, with PMID:2731651 as the donor publication. Its accessible abstract examines developmental actin expression and altered alpha-actin expression in BALB/c mice. Retain the established ortholog annotation as developmental context; do not reinterpret that study as a targeted Acta1 knockout or as direct proof of a differentiation-regulatory mechanism. ACTA1 structural assembly and contraction remain the core roles. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P68134 · Acta1 (Mus musculus, Swiss-Prot) SUPPORTS TRANSFER Mouse skeletal-actin ortholog with developmental-expression source PMID:2731651; retain developmental context without asserting a targeted Acta1 knockout. Supporting Evidence: PMID:2731651 examined the expression of this actin gene pair throughout the development of skeletal and cardiac muscle in BALB/c mice.
GO:0016887 ATP hydrolysis activity	ISS GO_REF:0000024	ACCEPT	Summary: Pig skeletal alpha-actin provides direct biochemical support for the orthologous ATPase activity. Reason: The ISS donor P68137 is pig ACTA1. PMID:24743229 uses purified endogenous pig skeletal muscle alpha-actin as the canonical control and reports phosphate release during polymerization (Figure 6D). The assay measures phosphate release, which can lag hydrolysis, so it does not directly equate release kinetics with cleavage kinetics. Together with the conserved actin nucleotide site and the UniProt ATP-to-ADP reaction, this supports ATP hydrolysis in human ACTA1. Actin hydrolysis is distinct from myosin ATP hydrolysis during the contractile power-stroke cycle. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P68137 · ACTA1 (Sus scrofa, Swiss-Prot) SUPPORTS TRANSFER Pig skeletal-actin control explicitly purified and assayed for phosphate release in PMID:24743229; supports conserved actin ATPase function. Supporting Evidence: PMID:24743229 Endogenous pig skeletal muscle α-actin was purified as described PMID:24743229 As expected, α-actin showed an even lower release of phosphate in the Ca2+-bound compared to the Mg2+-bound form.
GO:0010628 positive regulation of gene expression	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken smooth-muscle-actin source is identified, but conservation of positive regulation of gene expression in ACTA1 remains unresolved. Reason: The saved donor trace links chicken ACTA2/P08023 to an AgBase IDA for this term from PMID:10633868. The primary abstract describes SMA expression, antisense suppression and endothelial-mesenchymal transformation; the gene-expression assay underlying the donor IDA requires the inaccessible full paper. Human ACTA1 conservation of that regulatory activity remains unestablished. The saved analysis identifies chicken ACTA1/P68139 as the ortholog and a transfer block across muscle actins, excluding ACTB/ACTG1. These observations define a cross-paralog ISS and its recipient scope; they do not establish which regulatory mechanism is conserved. The 97.9% ACTA1/ACTA2 identity supports similarity but does not resolve this process-specific judgment. Retain UNDECIDED pending the donor assay and evidence of functional conservation or divergence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 · ACTA2 (Gallus gallus, Swiss-Prot) UNRESOLVED Saved AgBase IDA traces gene-expression regulation to PMID:10633868; the full assay and its conservation in ACTA1 remain unresolved. Supporting Evidence: PMID:10633868 During early development, SMA is expressed in various mesodermally derived tissues in a spatiotemporally restricted manner file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md The donor's evidence is sound, not weak: P08023 carries all five terms itself by IDA/IMP, and all five trace to one paper, PMID:10633868, an antisense-knockdown study of endothelial-mesenchymal transformation in chick cardiogenesis.
GO:0030027 lamellipodium	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken smooth-muscle-actin source is identified, but conservation of lamellipodial localization in ACTA1 remains unresolved. Reason: PMID:10633868 directly reports punctate chicken smooth-muscle alpha-actin in lamellipodia of invading endocardial mesenchymal cells. The saved donor trace records this localization as AgBase IDA on P08023. Lamellipodia are a distinct actin structure, and ACTA1 stress-fiber incorporation does not establish this localization. The source is a paralog despite the available chicken ACTA1/P68139 ortholog. The muscle-actin recipient pattern and high sequence identity identify a plausible structural relationship but do not resolve ACTA1 recruitment to lamellipodia. Full donor images and isoform-specific conservation evidence remain unavailable; the transfer is UNDECIDED rather than demonstrated to be conserved or lost. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 · ACTA2 (Gallus gallus, Swiss-Prot) UNRESOLVED Donor IDA and primary abstract support chick mesenchymal lamellipodia. Recruitment of ACTA1 to this structure remains unresolved. Supporting Evidence: PMID:10633868 distributed in a punctate manner in the lamellipodia/filopodia of invading mesenchymal cells. file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md The donor's evidence is sound, not weak: P08023 carries all five terms itself by IDA/IMP, and all five trace to one paper, PMID:10633868, an antisense-knockdown study of endothelial-mesenchymal transformation in chick cardiogenesis.
GO:0030175 filopodium	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken smooth-muscle-actin source is identified, but conservation of filopodial localization in ACTA1 remains unresolved. Reason: PMID:10633868 directly reports punctate chicken smooth-muscle alpha-actin in filopodia of invading endocardial mesenchymal cells, corresponding to the P08023 AgBase IDA in the saved trace. This localization requires recruitment to projecting actin bundles; the existing ACTA1 stress-fiber experiment examines a different structure. Chicken ACTA1/P68139 exists, so this is a cross-paralog ISS, not an orthology assertion. The recorded transfer across muscle actins but not ACTB/ACTG1 does not measure filopodial targeting or establish ACTA1-specific exclusion. The full donor localization experiment and evidence resolving conservation of this targeting remain unavailable. Keep the assertion UNDECIDED. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 · ACTA2 (Gallus gallus, Swiss-Prot) UNRESOLVED Donor IDA and primary abstract support chick mesenchymal filopodia. Conservation of filopodial localization in ACTA1 remains unresolved. Supporting Evidence: PMID:10633868 distributed in a punctate manner in the lamellipodia/filopodia of invading mesenchymal cells. file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md The donor's evidence is sound, not weak: P08023 carries all five terms itself by IDA/IMP, and all five trace to one paper, PMID:10633868, an antisense-knockdown study of endothelial-mesenchymal transformation in chick cardiogenesis.
GO:0044297 cell body	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken smooth-muscle-actin source is identified, but conservation of cell-body localization in ACTA1 remains unresolved. Reason: The saved trace links P08023 to an AgBase cell-body IDA from PMID:10633868, whose abstract describes projecting endothelial/mesenchymal cells but does not resolve the cell-body assay. The live GO definition describes the nucleus-containing portion of a projecting cell and excludes its projections. A mature skeletal-muscle fiber alone therefore does not establish this compartment assignment. Conversely, an annotation to ACTA1 is not restricted to mature fibers, and the available evidence does not exclude ACTA1 from every projecting cell state. The chicken ACTA1 ortholog and muscle-actin recipient distribution show the scope of the cross-paralog transfer, not conservation of this specific compartment. With the full donor experiment inaccessible and transfer unresolved, retain UNDECIDED. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 · ACTA2 (Gallus gallus, Swiss-Prot) UNRESOLVED Donor IDA is recovered, but the cell-body assay and conservation of the defined compartment in ACTA1 remain unresolved. Supporting Evidence: PMID:10633868 expressed homogeneously in the newly formed appendages of transforming endothelial/mesenchymal cells file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md The donor's evidence is sound, not weak: P08023 carries all five terms itself by IDA/IMP, and all five trace to one paper, PMID:10633868, an antisense-knockdown study of endothelial-mesenchymal transformation in chick cardiogenesis.
GO:0090131 mesenchyme migration	ISS GO_REF:0000024	UNDECIDED	Summary: The chicken smooth-muscle-actin source is identified, but conservation of mesenchyme migration in ACTA1 remains unresolved. Reason: The P08023 donor IMP is grounded in PMID:10633868: SMA-specific antisense reduced mesenchymal formation and TGF-beta-induced migratory appendages in chick atrioventricular endothelial cultures. This is a defined developmental migration context. The saved cross-paralog transfer reaches skeletal and cardiac muscle actins despite an available chicken ACTA1 ortholog; sequence similarity and recipient distribution alone do not establish conservation of the donor's regulated expression or migratory contribution. ACTA1 stress-fiber localization supplies no direct support for this process. The full perturbation experiments and evidence resolving ACTA1 participation in mesenchyme migration remain unavailable, so this ISS remains UNDECIDED. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08023 · ACTA2 (Gallus gallus, Swiss-Prot) UNRESOLVED Donor IMP concerns SMA-dependent chick endothelial-mesenchymal migration; conservation of that developmental contribution in ACTA1 remains unresolved. Supporting Evidence: PMID:10633868 Perturbation of SMA by antisense ODN also inhibited TGF beta-inducible migratory appendage formation in a cultured AV endothelial monolayer. file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md The donor's evidence is sound, not weak: P08023 carries all five terms itself by IDA/IMP, and all five trace to one paper, PMID:10633868, an antisense-knockdown study of endothelial-mesenchymal transformation in chick cardiogenesis.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	UNDECIDED	Summary: The reported ACTA1 localization in exosomes from expressed prostatic secretions in urine remains unresolved at the protein-identification level. Reason: PMID:23533145 is the cited proteomics study of exosomes from expressed prostatic secretions in urine. The main article is available, but the ACTA1-specific supplementary protein/peptide entry needed to resolve the assignment could not be recovered. The saved mature-chain digest finds 54 of 63 theoretical peptides shared with other human actins, including 29 shared with ACTB/ACTG1, and three independent ACTA1-distinguishing regions. It does not show which peptides this experiment detected. Skeletal-muscle enrichment and lack of a secretion signal do not disprove extracellular recovery. Keep the curator assertion unresolved pending its actual protein/peptide evidence, without converting hypothetical contamination or paralog ambiguity into a negative finding. Supporting Evidence: file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| shared with ≥1 other human actin \| 54 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| of those, shared with ACTB and/or ACTG1 \| 29 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md It does not refute the five HDA rows
GO:0072562 blood microparticle	HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d...	UNDECIDED	Summary: The reported ACTA1 localization in plasma microvesicles remains unresolved at the protein-identification level. Reason: PMID:22516433 is the cited proteomics study of plasma microvesicles. The abstract is available, but the original ACTA1 protein/peptide entry and full experimental evidence could not be recovered. The saved mature-chain digest finds 54 of 63 theoretical peptides shared with other human actins, including 29 shared with ACTB/ACTG1, and three independent ACTA1-distinguishing regions. It does not show which peptides this experiment detected. Skeletal-muscle enrichment and lack of a secretion signal do not disprove extracellular recovery. Keep the curator assertion unresolved pending its actual protein/peptide evidence, without converting hypothetical contamination or paralog ambiguity into a negative finding. Supporting Evidence: file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| shared with ≥1 other human actin \| 54 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| of those, shared with ACTB and/or ACTG1 \| 29 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md It does not refute the five HDA rows
GO:0005576 extracellular region	HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter...	UNDECIDED	Summary: The reported ACTA1 localization in tear fluid remains unresolved at the protein-identification level. Reason: PMID:23580065 is the cited proteomics study of tear fluid. The abstract is available, but the original ACTA1 protein/peptide entry and full experimental evidence could not be recovered. The saved mature-chain digest finds 54 of 63 theoretical peptides shared with other human actins, including 29 shared with ACTB/ACTG1, and three independent ACTA1-distinguishing regions. It does not show which peptides this experiment detected. Skeletal-muscle enrichment and lack of a secretion signal do not disprove extracellular recovery. Keep the curator assertion unresolved pending its actual protein/peptide evidence, without converting hypothetical contamination or paralog ambiguity into a negative finding. Supporting Evidence: file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| shared with ≥1 other human actin \| 54 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| of those, shared with ACTB and/or ACTG1 \| 29 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md It does not refute the five HDA rows
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	UNDECIDED	Summary: The reported ACTA1 localization in parotid exosomes remains unresolved at the protein-identification level. Reason: PMID:19199708 is the cited proteomics study of parotid exosomes. The main article is available, but the ACTA1-specific supplementary protein/peptide entry needed to resolve the assignment could not be recovered. The saved mature-chain digest finds 54 of 63 theoretical peptides shared with other human actins, including 29 shared with ACTB/ACTG1, and three independent ACTA1-distinguishing regions. It does not show which peptides this experiment detected. Skeletal-muscle enrichment and lack of a secretion signal do not disprove extracellular recovery. Keep the curator assertion unresolved pending its actual protein/peptide evidence, without converting hypothetical contamination or paralog ambiguity into a negative finding. Supporting Evidence: file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| shared with ≥1 other human actin \| 54 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| of those, shared with ACTB and/or ACTG1 \| 29 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md It does not refute the five HDA rows
GO:0070062 extracellular exosome	HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells.	UNDECIDED	Summary: The reported ACTA1 localization in trabecular-meshwork cell exosomes remains unresolved at the protein-identification level. Reason: PMID:21362503 is the cited proteomics study of trabecular-meshwork cell exosomes. The main article is available, but the ACTA1-specific supplementary protein/peptide entry needed to resolve the assignment could not be recovered. The saved mature-chain digest finds 54 of 63 theoretical peptides shared with other human actins, including 29 shared with ACTB/ACTG1, and three independent ACTA1-distinguishing regions. It does not show which peptides this experiment detected. Skeletal-muscle enrichment and lack of a secretion signal do not disprove extracellular recovery. Keep the curator assertion unresolved pending its actual protein/peptide evidence, without converting hypothetical contamination or paralog ambiguity into a negative finding. Supporting Evidence: file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| shared with ≥1 other human actin \| 54 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md \| of those, shared with ACTB and/or ACTG1 \| 29 \| file:human/ACTA1/ACTA1-bioinformatics/RESULTS.md It does not refute the five HDA rows
GO:0005829 cytosol	TAS Reactome:R-HSA-390593	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of ATP hydrolysis by myosin. The event describes the actin-containing contractile apparatus, with its reaction chemistry assigned to myosin or troponin. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-390593 The cleft closes like a clam shell around the ATP molecule, triggering a large shape change that causes the myosin head to release actin and be displaced along the actin filament by a distance of about 5 nm.
GO:0005829 cytosol	TAS Reactome:R-HSA-390595	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of calcium binding to troponin C. The event describes the actin-containing contractile apparatus, with its reaction chemistry assigned to myosin or troponin. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-390595 Troponin (Tn) is the central regulatory protein of striated muscle contraction.
GO:0005829 cytosol	TAS Reactome:R-HSA-390597	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of ADP release from myosin. The event describes the actin-containing contractile apparatus, with its reaction chemistry assigned to myosin or troponin. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-390597 The weak binding of the myosin head to the new site on the actin filament causes release of the inorganic phosphate produced by ATP hydrolysis, concomitantly with the tight binding of the head to actin.
GO:0005829 cytosol	TAS Reactome:R-HSA-390598	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of ATP binding to myosin. The event describes the actin-containing contractile apparatus, with its reaction chemistry assigned to myosin or troponin. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-390598 A molecule of ATP binds to the large cleft on the side of the myosin head farthest from the actin filament and immediately causes a slight change in the conformation of the domains that make up the actin-binding site.
GO:0005829 cytosol	TAS Reactome:R-HSA-9914537	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of dystroglycan binding to AGRN/HSPG2. The adhesion event supplies a generic actin pathway context; ACTA1-specific participation in that adhesion mechanism is not established by its summary. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-9914537 Alpha-dystroglycan (DAG1(30-653)) binds G domain-like sequences in other extracellular matrix molecules such as AGRN (agrin) PMID:15198992
GO:0005829 cytosol	TAS Reactome:R-HSA-9934294	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of vinculin recruitment to the CDH1 complex. The adhesion event supplies a generic actin pathway context; ACTA1-specific participation in that adhesion mechanism is not established by its summary. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-9934294 VCL may stabilize the interaction between CTNNA1 and F-actin PMID:15198992
GO:0005829 cytosol	TAS Reactome:R-HSA-9934410	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of CDH1 trans-dimer formation. The adhesion event supplies a generic actin pathway context; ACTA1-specific participation in that adhesion mechanism is not established by its summary. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-9934410 CDH1 clusters in both interacting cells are surrounded by the cytosolic F-actin meshwork PMID:15198992
GO:0005829 cytosol	TAS Reactome:R-HSA-9934486	ACCEPT	Summary: Cytosol is a core compartment of ACTA1 actin assembly and contractile function. Reason: ACTA1 forms intracellular actin filaments and the skeletal-muscle contractile apparatus; cytosol is the broad source compartment containing this core machinery. Reactome exports that location in the context of CTNNA1 recruitment of F-actin to the CDH1 complex. The adhesion event supplies a generic actin pathway context; ACTA1-specific participation in that adhesion mechanism is not established by its summary. The accepted assertion is ACTA1 cytosol localization, supported independently by its filament biology and wild-type ACTA1-EGFP cytoplasmic/stress-fiber localization in PMID:15198992. Supporting Evidence: Reactome:R-HSA-9934486 CTNNA1 (alpha-catenin) is responsible for the recruitment of F-actin polymers to the CDH1 complex PMID:15198992
GO:0015629 actin cytoskeleton	IMP PMID:15198992 Evidence for a dominant-negative effect in ACTA1 nemaline my...	ACCEPT	Summary: Human patient-muscle experiments place ACTA1 in insoluble actin filaments. Reason: PMID:15198992 identifies mutant and wild-type skeletal actin in soluble and insoluble muscle fractions and analyzes altered polymerization. These data directly support the actin-cytoskeleton location. The full paper distinguishes patient-muscle observations from localization of tagged constructs in C2C12 cells; both are legitimate experimental contexts. Supporting Evidence: PMID:15198992 present within insoluble actin filaments isolated from muscle from two ACTA1 NM
GO:0030017 sarcomere	IDA PMID:1423520 Differentiation of human skeletal muscle cells in culture: m...	ACCEPT	Summary: Human differentiating myotubes show skeletal alpha-actin in sarcomeric striations. Reason: PMID:1423520 explicitly tracks skeletal muscle alpha-actin by immunofluorescence during human myoblast differentiation, although titin and desmin appear in the title. Mature myotubes display cross-striated alpha-actin. This supports sarcomere localization without inferring an unmeasured compartment or rejecting the curator on the basis of the title. Supporting Evidence: PMID:1423520 vimentin as well as the sarcomeric constituents alpha-actin, alpha-actinin, PMID:1423520 cross-striations, while vimentin was no longer detected. We conclude that human
GO:0005200 structural constituent of cytoskeleton	TAS PMID:10508519 Mutations in the skeletal muscle alpha-actin gene in patient...	ACCEPT	Summary: ACTA1 is the structural actin subunit of muscle thin filaments. Reason: The ACTA1 myopathy study PMID:10508519 places the encoded protein in the actin-containing thin filament and reports disease-causing variants. Its structural role is consistent with recombinant human ACTA1 polymerization (PMID:12849983), patient filament abnormalities and the independent PAINT assertion. Supporting Evidence: PMID:10508519 Muscle contraction results from the force generated between the thin filament
GO:0006936 muscle contraction	TAS PMID:10508519 Mutations in the skeletal muscle alpha-actin gene in patient...	MODIFY	Summary: The cited human skeletal-muscle disease source supports the skeletal contraction subtype. Reason: PMID:10508519 links the actin-containing thin filament to force generation and identifies pathogenic ACTA1 variants in skeletal-muscle myopathy. Refine the broad process to GO:0003009 to express that supported tissue context. ACTA1 contributes the structural filament and myosin-binding interface used for force transmission. This refinement does not assert that ACTA1 is absent from the heart or that every disease allele has an exclusively skeletal phenotype. Proposed replacements: skeletal muscle contraction Supporting Evidence: PMID:16288873 gestation and is the exclusive isoform expressed in muscle from infancy through PMID:16288873 birth. Although alpha-skeletal actin is thought to be the predominant sarcomeric PMID:10508519 that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are
GO:0005884 actin filament	IDA PMID:12849983 Production of human skeletal alpha-actin proteins by the bac...	ACCEPT	Summary: Recombinant human skeletal alpha-actin forms polymerized filaments. Reason: PMID:12849983 reports native-like human recombinant protein that undergoes polymerization/depolymerization cycles. This directly supports the actin-filament location and agrees with the structural role in muscle. Supporting Evidence: PMID:12849983 similarly to native actin, as shown by DNase I affinity purification, Western
GO:0043531 ADP binding	TAS PMID:10508519 Mutations in the skeletal muscle alpha-actin gene in patient...	ACCEPT	Summary: ADP binding is the product-bound state of actin nucleotide cycling. Reason: ADP is the product-bound nucleotide state of skeletal alpha-actin. In PMID:24743229, endogenous pig skeletal-muscle alpha-actin was purified and examined in ATP and ADP forms; Figure 7 includes the nucleotide-exchange control. This orthologous biochemical evidence supports the conserved nucleotide-binding function underlying the human TAS assertion. It does not provide a human ACTA1 ADP-binding affinity. Supporting Evidence: PMID:24743229 Endogenous pig skeletal muscle α-actin was purified as described PMID:24743229 Both ATP and ADP forms of α-actin remain monomeric in the same conditions.
GO:0005865 striated muscle thin filament	IDA PMID:15198992 Evidence for a dominant-negative effect in ACTA1 nemaline my...	ACCEPT	Summary: ACTA1 contributes to the striated-muscle thin filament. Reason: PMID:15198992 supplies patient-muscle filament evidence and, in the recovered full original Figure 5B(viii), striated incorporation of wild-type ACTA1-EGFP after myoblast differentiation. The source therefore supports the specific thin-filament location. Patient insoluble fractions alone need not be interpreted as excluding additional actin aggregates. Supporting Evidence: PMID:15198992 present within insoluble actin filaments isolated from muscle from two ACTA1 NM
GO:0005524 ATP binding	TAS PMID:10508519 Mutations in the skeletal muscle alpha-actin gene in patient...	ACCEPT	Summary: ATP binding supports actin assembly and nucleotide cycling. Reason: ATP binding supports the conserved nucleotide cycle of skeletal alpha-actin and its polymerization-associated hydrolysis. PMID:24743229 directly compares purified pig skeletal-muscle alpha-actin in ATP and ADP forms and measures phosphate release. These orthologous controls corroborate the human TAS assignment while leaving human-specific nucleotide affinities unmeasured in this source. Supporting Evidence: PMID:24743229 Endogenous pig skeletal muscle α-actin was purified as described PMID:24743229 Both ATP and ADP forms of α-actin remain monomeric in the same conditions.
GO:0017022 myosin binding	TAS PMID:10508519 Mutations in the skeletal muscle alpha-actin gene in patient...	ACCEPT	Summary: The actin-myosin interaction forms the contractile interface of skeletal-muscle thin filaments. Reason: PMID:10508519 describes force generation at the actin-containing thin-filament/myosin interface. PMID:16945537 additionally reports altered sliding speed of actin isolated from ACTA1-mutant patient muscle. Myosin binding is a specific, informative molecular function of the thin-filament protomer. Supporting Evidence: PMID:10508519 Muscle contraction results from the force generated between the thin filament PMID:16945537 isolated from the muscle biopsy and examined by in vitro motility assay. The
GO:0001725 stress fiber	IDA PMID:15198992 Evidence for a dominant-negative effect in ACTA1 nemaline my...	KEEP AS NON CORE	Summary: Wild-type ACTA1-EGFP localizes to stress fibers in cultured myoblasts. Reason: The full original PMID:15198992 was recovered from the University of Geneva archive (DOI:10.1093/hmg/ddh185). Results on journal page 1733 and Figure 5A show wild-type ACTA1-EGFP in stress fibers in C2C12 myoblasts; differentiated cells also show sarcomeric incorporation in Figure 5B(viii). This supports a real culture-context localization, retained as non-core relative to the mature muscle thin filament. Local publication cache remains abstract-only; the full-paper route and figure are documented in notes. Supporting Evidence: PMID:15198992
GO:0005515 protein binding	IPI PMID:12849983 Production of human skeletal alpha-actin proteins by the bac...	REMOVE	Summary: Human recombinant ACTA1 binds DNase I in an affinity-purification assay. Reason: PMID:12849983 explicitly reports DNase I affinity purification of human recombinant skeletal alpha-actin. The binding result is credible, but GO:0005515 does not explain the functional mechanism. Remove the generic term under the binding policy, without declaring the interaction false. Affinity purification alone does not establish deoxyribonuclease inhibitor activity, so no inhibitory replacement is proposed. Supporting Evidence: PMID:12849983 similarly to native actin, as shown by DNase I affinity purification, Western
GO:0030240 skeletal muscle thin filament assembly	IMP PMID:11333380 Nemaline myopathy caused by mutations in the muscle alpha-sk...	ACCEPT	Summary: ACTA1 supplies the polymerizing structural component of skeletal-muscle thin filaments. Reason: ACTA1 supplies the polymerizing structural component of skeletal-muscle thin filaments. PMID:11333380 reports disorganization and whorling of those filaments in ACTA1 myopathy, and recombinant human ACTA1 undergoes polymerization/depolymerization in PMID:12849983. Together these observations support direct structural participation in thin-filament assembly. Supporting Evidence: PMID:11333380 disruption, and "whorling" of actin thin filaments. The percentage of fibers
GO:0051371 muscle alpha-actinin binding	IDA PMID:16945537 Fatal hypertrophic cardiomyopathy and nemaline myopathy asso...	NEW	Summary: Retain the existing proposal for binding to Z-line muscle alpha-actinin. Reason: PMID:16945537 reports a direct affinity measurement using actin from a human ACTA1 K336E muscle biopsy and a comparison with normal actin. The partner is explicitly described as Z-line alpha-actinin, matching the muscle-isoform scope of GO:0051371. Retain the pre-existing IDA proposal without inventing an ACTN2 or ACTN3 accession. The biopsy contained 28% mutant actin, so the reported ten-fold affinity change is a property of a mixture. UniProt residue-level interaction regions are inferred from rabbit ACTA1 and are not independent human mapping experiments. Supporting Evidence: PMID:16945537 the affinity of actin for the Z-line protein alpha-actinin was reduced 10 fold. PMID:16945537 electrophoresis showed 28% mutant actin present in his muscle biopsy.

Gene Description

Existing Annotations Review

Core Functions

ACTA1 polymerizes into the actin backbone of skeletal-muscle thin filaments, contributing their structural integrity and directly participating in thin-filament assembly.

ACTA1 binds ATP and hydrolyzes it during filament assembly. Hydrolysis and subsequent phosphate release influence actin filament dynamics; oriented subunit assembly gives the filament structural polarity.

ACTA1 provides the myosin-binding surface and force-transmitting thin filament used in skeletal-muscle contraction. Myosin heads, rather than actin subunits, couple the power stroke to the myosin ATPase cycle.

Binding to muscle alpha-actinin connects the ACTA1 thin filament to the Z-disc organization machinery. Human patient-muscle actin exhibits altered alpha-actinin affinity, supporting this specific interaction.

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