ACTR1A (alpha-centractin, Arp1) is the actin-related protein that forms the structural backbone of dynactin, the essential cofactor of cytoplasmic dynein-1. Eight copies of ACTR1A together with a single beta-actin subunit polymerise into a short two-protofilament mini-filament about 37 nm long, capped by the CAPZA1-CAPZB heterodimer at one end and by ACTR10 (Arp11) with the p25-p27-p62 pointed-end module at the other, and coated on three faces by the shoulder formed from p150Glued, p50/dynamitin and p24. The remaining face of the filament is the platform on which the dynein heavy-chain tails and a coiled-coil cargo adaptor such as BICD2, BICDR1 or HOOK3 dock; because the filament is doubly capped and of exactly defined length, its translational symmetry matches that of the dynein tail and its length holds the two heavy chains apart in the conformation required for processive motility. ACTR1A therefore contributes structure and binding surface rather than motor or catalytic activity, and through dynactin it supports minus-end-directed transport of vesicles and organelles along microtubules, Golgi and endosome positioning, retrograde traffic from the Golgi to the ER, microtubule anchoring at the centrosome, and cortical force generation that orients the mitotic spindle. Unlike conventional actin it is not a dynamic polymer: essentially all cellular ACTR1A is found within the assembled 20S dynactin complex with no free pool, and the filament neither treadmills nor changes length. It retains the actin nucleotide-binding cleft and is found with ADP bound in every protomer of the human complex. A minor paralog, ACTR1B (beta-centractin), is incorporated into the same complex but at roughly one fifteenth the abundance of ACTR1A.
Definition: The aggregation, arrangement and bonding together of a set of components to form a dynactin complex, including polymerisation of actin-related protein 1 into a mini-filament of defined length, capping of that filament at both ends, and attachment of the shoulder and pointed-end modules.
Justification: GO can express dynactin as a structure (GO:0005869) and as a binding target (GO:0034452 dynactin binding) but has no term for its assembly: a QuickGO ontology search for 'dynactin' returns only those two terms plus two obsolete ones. That is a real gap, because dynactin assembly is the only process in which ACTR1A's polymerisation activity is deployed, and it is mechanistically distinctive rather than generic - the shoulder and its extended p50 regions recruit exactly eight Arp1 subunits and act as a molecular ruler, CapZ alpha-beta caps the barbed end and Arp11 the pointed end, and free Arp1 polymers by contrast vary in length. Without such a term the only available annotation for ACTR1A's assembly role is the generic GO:0051258 protein polymerization, which says nothing about the product. GO already has the exact sibling for the partner complex, GO:0070286 axonemal dynein complex assembly.
Parent term: protein-containing complex assembly
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030473 nuclear migration along microtubule | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dynein-dynactin does move nuclei along microtubules in animal cells, and ACTR1A is an obligate structural subunit of dynactin, so involvement is likely true - but it is one cargo among many and there is no mammalian experimental support. Kept as a non-core process. Reason: GO:0030473 is defined as directed movement of the nucleus along microtubules mediated by motor proteins, which is a genuine dynein-dynactin output; since ACTR1A forms the dynactin backbone the involved_in call is defensible and I am not disputing it. It is not core, for two reasons. First, all interpretable donor evidence is fungal and lineage-specific: A. nidulans nudK/Arp1 from a nuclear-distribution mutant screen, and S. pombe arp1 whose own IMP is to the child term GO:0030989, the meiotic horsetail oscillation led by an astral array from a spindle pole body. Second, the one mammalian donor row is wrong: pig ACTR1A carries GO:0030989 by IDA sourced from a cryo-EM structure paper (PMID:36071160), which cannot evidence a meiotic movement process. So the mammalian support for this branch is an artefact, leaving a fungal-only inference for a process that is real in mammals but untested for this gene. Nuclear migration is a cargo-specific specialisation of the general transport role captured elsewhere in this review. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH SOURCE MISCITATION Sources checked: PANTHER:PTN000233666 · PANTHER tree node PTN000233666 UNRESOLVED PANTHER internal tree node, not a gene product, so it carries no evidence of its own and cannot be interrogated; reported as unresolvable-in-principle rather than simply unresolved. PomBase:SPBC1347.12 · S. pombe arp1 (O94630, Swiss-Prot) SUPPORTS SOURCE BUT NOT TARGET Carries its own IMP, but to the child term GO:0030989 dynein-driven meiotic oscillatory nuclear movement (PMID:25736293) - the fission-yeast meiotic horsetail oscillation, driven from a spindle pole body. UniProtKB:F2Z5G5 · Sus scrofa ACTR1A (Swiss-Prot) SOURCE BAD Its only experimental annotation under this branch is GO:0030989 with evidence IDA, assigned by ComplexPortal from PMID:36071160 - a cryo-EM structure paper that cannot be a direct assay of a meiotic nuclear-oscillation process, for a term defined around a spindle pole body that pigs do not have. The same row was applied to DCTN1/2/4/5 and CAPZA1/B and propagated to rat by ISO. UniProtKB:Q5BBX7 · A. nidulans ANIA_01953 / nudK (Q5BBX7, unreviewed TrEMBL, submitted name 'Uncharacterized protein') SUPPORTS SOURCE BUT NOT TARGET Genuine IMP for GO:0030473 itself from a nuclear-distribution mutant screen (PMID:10467007); unreviewed entry, so its protein name is not usable as evidence, only its curated GO evidence. Supporting Evidence: PMID:10467007 We have cloned one of the genes, nudK, and determined that it encodes the actin-related protein Arp1, which is a component of the dynactin complex. This provides the first evidence that dynactin is involved in nuclear migration in A. nidulans. |
| GO:0106006 cytoskeletal protein-membrane anchor activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: A fission-yeast cortical-anchoring activity transferred onto the filament-core subunit. In human cells the cortical anchor is Galphai-LGN-NuMA and dynactin is the anchored partner, and none of ACTR1A's structurally resolved contacts is a membrane or membrane protein. Over-annotated. Reason: GO:0106006 requires an activity that brings a cytoskeletal protein or complex together with a plasma membrane lipid or membrane-associated protein so as to hold the cytoskeleton at a cortical location. Three things argue against transferring it to human ACTR1A. (i) Every ACTR1A contact resolved in the human dynactin structure is intra-complex - neighbouring Arp1 protomers, beta-actin, ACTR10, CAPZA1/CAPZB, the p50 shoulder - plus the dynein heavy-chain tail; no membrane or membrane protein. (ii) In human mitosis the cortical link is supplied by Galphai-LGN-NuMA and the dependency runs the other way: LGN is required for cortical dynein-dynactin, so the anchoring activity sits upstream of dynactin rather than in it. (iii) The sole interpretable donor is one EXP annotation on S. pombe arp1, in a system where Num1/Mcp5 is the cortical anchor and dynactin cooperates with it; that source annotation is sound, which is precisely why this is a propagation problem rather than a bad source. I stop at MARK_AS_OVER_ANNOTATED rather than REMOVE because the contributes_to qualifier only asserts that dynactin as a complex has the activity, and in fission yeast dynactin genuinely is required for cortical dynein anchoring; the mammalian case is untested, not refuted, and untested is not the same verdict as wrong. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN007551901 · PANTHER tree node PTN007551901 UNRESOLVED PANTHER internal tree node, not a gene product; no evidence of its own. PomBase:SPBC1347.12 · S. pombe arp1 (O94630, Swiss-Prot) SUPPORTS SOURCE BUT NOT TARGET Carries GO:0106006 contributes_to with evidence EXP from PMID:25736293, where the cortical anchor is Num1/Mcp5 and dynactin cooperates with it. Sound for fission yeast; the human cortical anchor is Galphai-LGN-NuMA. Supporting Evidence: PMID:25736293 These subunits transiently colocalized with dynein foci at the cell cortex and were essential for the cortical anchoring of dynein. PMID:22327364 we found that LGN was required for the cortical localization of dynein-dynactin PMID:25814576 They bind adjacent clefts between Arp1-D & F (chain-1) and Arp1-F & β-actin-H (chain-2) (Fig. 5F,G). |
| GO:0005869 dynactin complex | IBA GO_REF:0000033 | ACCEPT | Summary: Core and correct: ACTR1A is the subunit dynactin is built around, in eight copies. Four of the five resolvable donors carry their own experimental evidence for dynactin membership, and the human structure settles it directly. Reason: This is the defining annotation for the gene. It does not rest on phylogenetic inference alone: S. cerevisiae ARP1, S. pombe arp1, pig ACTR1A and C. elegans arp-1 each carry their own IDA or IPI for GO:0005869, and human ACTR1A is modelled in eight copies in the human dynactin cryo-EM structure. A claim that the donors carry only the same family-level inference would be factually false here. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000233666 · PANTHER tree node PTN000233666 UNRESOLVED PANTHER internal tree node, not a gene product, so it carries no evidence of its own and cannot be interrogated; reported as unresolvable-in-principle rather than simply unresolved. PomBase:SPBC1347.12 · S. pombe arp1 (O94630, Swiss-Prot) SUPPORTS TRANSFER Own IPI for GO:0005869 (PMID:25736293). SGD:S000001171 · S. cerevisiae ARP1/ACT5 (P38696, Swiss-Prot) SUPPORTS TRANSFER Own IDA and IPI for GO:0005869 (PMID:9658168, PMID:18245366), and its own IDA for GO:0005200. UniProtKB:F2Z5G5 · Sus scrofa ACTR1A (Swiss-Prot) SUPPORTS TRANSFER Own IPI for GO:0005869 (PMID:33734450). WB:WBGene00013168 · C. elegans arp-1 (maps to TWO unreviewed TrEMBL entries, Q9NA98 and U4PR70; no reviewed entry exists) SUPPORTS TRANSFER Q9NA98 carries its own IDA for GO:0005869 (PMID:20964796); the sibling entry U4PR70 has no annotations. Both are unreviewed, so neither entry's name may be cited as evidence of function. Supporting Evidence: PMID:25814576 Dynactin is built around a filament of actin related protein 1 (Arp1). PMID:25814576 We confirmed the presence of Arp1 and β-actin at an 8:1 ratio by mass spectrometry-based label-free quantitative proteomic analysis file:human/ACTR1A/ACTR1A-uniprot.txt The filament contains 8 copies of ACTR1A and 1 ACTB. file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md ACTR1A protomers modelled: **8** (chains A, B, C, D, E, F, G, I); the modelled sequence is 100.0% identical to UniProt P61163. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Correct location from the UniProt subcellular-location mapping, and independently supported by the IDA row below. Not the core site of action. Reason: Dynein-dynactin anchors microtubule minus ends at the centrosome, and ACTR1A has been detected there directly, so the term is right; the action matches the IDA row for the same term deliberately. This subcellular-location mapping and the IDA row are two routes to the same fact. |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The less specific parent of the centrosome annotation the gene already carries by IDA. True, redundant, non-core. Reason: GO:0005813 centrosome is already annotated with better evidence and is a descendant of GO:0005815, so this ARBA row adds no information. It is not wrong and there is no per-gene way to retire an ARBA inference, so it is kept and flagged as redundant rather than modified. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: True but subsumed: GO:0005869 dynactin complex, already annotated, is a descendant of cytoskeleton. Reason: QuickGO's ancestor closure for GO:0005869 includes GO:0005856 (and GO:0015629 actin cytoskeleton), so this subcellular-location mapping is a strict generalisation of an annotation the gene already has. Retained as correct but uninformative. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | ACCEPT | Summary: The keyword/subcellular-location mapping of the same cortical localisation that the IDA row below establishes directly. Reason: UniProt's cell-cortex line is itself sourced from PMID:22327364, so this row and the IDA row are the same observation reaching GOA by two routes; the action matches the IDA row deliberately. The cortical pool is a regulated, functional site where dynein-dynactin generates the pulling forces that position the mitotic spindle. Supporting Evidence: file:human/ACTR1A/ACTR1A-uniprot.txt cell cortex {ECO:0000269|PubMed:22327364}. |
| GO:0005938 cell cortex | IDA PMID:22327364 Chromosome- and spindle-pole-derived signals generate an int... | ACCEPT | Summary: Direct imaging of Arp1A at the mitotic cell cortex in HeLa cells, where its accumulation is asymmetric and spindle-pole-regulated. Sound and specific. Reason: ACTR1A (Arp1A) was imaged at the cell cortex and, unlike LGN, NuMA and Galphai, its cortical pool is asymmetric and negatively regulated by spindle-pole proximity, so this is a regulated functional localisation rather than an incidental one. The construct was a GFP fusion, which is the standard basis for an IDA localisation call in GO (GO_REF:0000054 exists precisely for fusion-protein localisation), so the evidence code is appropriate. Note that the same paper shows LGN is required for this localisation, which is what argues against giving ACTR1A a membrane-anchoring molecular function. Supporting Evidence: PMID:22327364 In HeLa cells, LGN localizes to the cell cortex from prometaphase through telophase (Fig. 1a), whereas dynein and the dynactin subunit Arp1A accumulate at the cell cortex subsequently to LGN PMID:22327364 In contrast, Arp1A accumulated asymmetrically at the cell cortex during metaphase such that it is preferentially localized to the cortex that is distal to the mitotic spindle |
| GO:0005515 protein binding | IPI PMID:28394342 Regulation of spindle integrity and mitotic fidelity by BCCI... | KEEP AS NON CORE | Summary: A real, isoform-resolved partner (BCCIP alpha / Q9P287-2), but the pull-down captured intact dynactin, so it does not localise a binding surface to ACTR1A and cannot be upgraded to an informative ACTR1A-specific molecular function. Reason: The evidence is better than a screen hit: GST-BCCIPalpha, but not BCCIPbeta or GST, pulled down Arp-1 from mitotic lysate, matching GOA's with-value of the alpha isoform Q9P287-2. That is a genuine partner and I am not discarding it. But p150Glued came down in the same pull-down, i.e. what was captured was the assembled dynactin complex, so the experiment shows BCCIPalpha binds dynactin, not that it contacts ACTR1A. Project guidance is to replace bare protein binding with an informative term, and I decline to do so here because no informative ACTR1A-specific molecular function is licensed by this experiment; inventing one would be worse than keeping the partner record. Retained as a non-core interaction record with that caveat. Supporting Evidence: PMID:28394342 BCCIPα, but not BCCIPβ or GST itself, was sufficient to pull down the dynactin components, p150 glued and Arp-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2213248 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Transport of antigen loaded MHC II molecules to surface'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574840 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'AJUBA facilitates AURKA autophosphorylation'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574845 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'AJUBA binds centrosome-associated AURKA'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000310 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'AURKA phosphorylates PLK1'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000319 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'BORA binds PLK1 and AURKA'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380272 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Plk1-mediated phosphorylation of Nlp'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380283 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380294 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Loss of C-Nap-1 from centrosomes'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380303 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Dissociation of Phospho-Nlp from the centrosome'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380311 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Recruitment of Plk1 to centrosomes'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380316 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Association of NuMA with microtubules'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380455 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Recruitment of CDK11p58 to the centrosomes'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380508 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Translocation of NuMA to the centrosomes'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'RAB3IP stimulates nucleotide exchange on RAB8A'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626220 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'C2CD3 binds the mother centriole'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'CP110 and CEP97 dissociate from the centriole'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'The distal appendage proteins recruit TTBK2'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Recruitment of transition zone proteins'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'MARK4 binds ODF2 in the centriole'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809003 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'ERGIC-to-Golgi vesicles bind dynein:dynactin'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809006 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Vesicle is tethered through binding GOLGA2:GORASP1, GOLGB1 and the COG complex'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8849350 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'RAB6:GTP displaces PAFAH1B1 from dynein:dynactin complex'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8849353 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'Dynein drives COPI-independent retrograde traffic from the Golgi to the ER'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853405 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'TPX2 binds AURKA at centrosomes'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853419 | KEEP AS NON CORE | Summary: Cytosolic localisation asserted by Reactome for the dynactin complex as a participant in the reaction 'TPX2 promotes AURKA autophosphorylation'. Correct but low-information, and one of 27 identical rows. Reason: Dynactin is a soluble cytoplasmic 20S complex, so cytosol is correct - and PMID:7696711 showed both centractin isoforms reside predominantly in the cytosolic fraction as part of that complex with no free pool. The annotation is nonetheless low-information and structurally redundant: GOA carries 27 identical cytosol rows, one per Reactome reaction in which the dynactin complex appears as a participant, which is a reaction-level compartment export rather than 27 independent observations. Several of the reactions concern centriole and ciliogenesis events with no ACTR1A-specific evidence at all; ACTR1A is present only because Reactome lists dynactin among the participants. Kept as a correct non-core location. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: Detection of a cytosolic dynactin subunit in a prostatic-secretion exosome proteome. Peptides were genuinely found, but this is the standard cytoskeletal-contaminant pattern rather than a functional location. Reason: ACTR1A has no signal peptide or transmembrane segment, is an obligate subunit of a 1 MDa cytoplasmic motor cofactor with no free pool, and no functional study places any part of dynactin outside the cell. High-throughput exosome proteomes routinely recover abundant cytoskeletal and cytoskeleton-associated proteins. Marked as over-annotated rather than removed because the mass-spectrometric detection itself is not in dispute. Supporting Evidence: PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Second exosome-proteome detection, this time urinary. Same assessment as the prostatic-secretion row: real peptides, not a functional location. Reason: Two independent high-throughput exosome proteomes recovering an abundant cytosolic protein increases confidence that the peptides are real, not that the protein functions extracellularly. ACTR1A is a core subunit of a cytoplasmic complex with no free pool and no secretory features. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: Centrosomal localisation from a human centrosome study combining proteomics with localisation validation. Consistent with the long-established role of dynein-dynactin in anchoring microtubules at the centrosome. Reason: Independent centrosome proteomics (PMID:14654843, cited by UniProt for the same location) reaches the same conclusion, and dynactin's centrosomal pool is functionally characterised: dynein-dynactin anchors microtubule minus ends there. Accepted as a genuine site of action, and carried into core_functions.locations. |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | KEEP AS NON CORE | Summary: Fusion-protein localisation to the cytoplasm. Correct and very general. Reason: A true but maximally general location, subsumed in practice by the cytosol and dynactin-complex annotations. Retained because the observation is sound. |
| GO:0005869 dynactin complex | TAS PMID:7696711 Beta-centractin: characterization and distribution of a new ... | ACCEPT | Summary: Author statement from the paper that separated alpha- from beta-centractin and showed both are dynactin subunits, with alpha dominant at about 15:1. Reason: The cited paper discriminated the two centractin isoforms with isoform-specific antibodies and two-dimensional gels and found both in the 20S dynactin complex, alpha in about fifteen-fold excess, with no free pool of either. Although the title foregrounds beta-centractin, the paper explicitly characterises alpha-centractin, so this is not a paralog mis-attribution. It is also the quantitative basis for treating ACTR1A rather than ACTR1B as the filament subunit. Supporting Evidence: PMID:7696711 The isoforms were found in a constant ratio of approximately 15:1 (alpha:beta) in the dynactin complex. PMID:7696711 Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. |
| GO:0005875 microtubule associated complex | TAS PMID:7696711 Beta-centractin: characterization and distribution of a new ... | MODIFY | Summary: A strict ancestor of GO:0005869 dynactin complex, annotated from the very same reference. Should be collapsed onto the child. Reason: QuickGO's ancestor closure for GO:0005869 includes GO:0005875, and both rows cite PMID:7696711, so the gene is annotated to a term and its parent from one evidence line. The paper supports the specific term - it identifies centractin as a component of the 20S dynactin complex - so the informative call is the child. The general phrasing in the abstract, an actin-related protein localized to microtubule-associated structures, is what generated the parent term. Proposed replacements: dynactin complex Supporting Evidence: PMID:7696711 an isoform of centractin, an actin-related protein localized to microtubule-associated structures |
| GO:0016192 vesicle-mediated transport | TAS PMID:1528266 A vertebrate actin-related protein is a component of a multi... | MODIFY | Summary: The founding centractin paper reports microtubule-based vesicle motility specifically, so the generic vesicle-mediated transport term under-describes its own evidence. Reason: GO:0016192 covers all vesicle-mediated transport including actin-myosin-driven and non-cytoskeletal routes, and the cited paper draws exactly the opposite contrast: it argues that centractin, unlike conventional actins acting with myosin, works in a microtubule-based system, as part of the dynactin activator of dynein-driven vesicle movement. GO:0047496 vesicle transport along microtubule captures that without over-claiming directionality, which the paper does not measure for ACTR1A itself. Proposed replacements: vesicle transport along microtubule Supporting Evidence: PMID:1528266 Actin-RPV is a major component of the dynactin complex, an activator of dynein-driven vesicle movement, indicating that unlike conventional actins which work in conjunction with myosin motors, actin-RPV may be involved in cytoplasmic movements via a microtubule-based system. |
| GO:0005200 structural constituent of cytoskeleton | IDA PMID:40186871 The Chlamydia effector Dre1 binds dynactin to reposition hos... | NEW | Summary: Restores the molecular function ACTR1A has lost. Eight ACTR1A protomers build the dynactin mini-filament; the human cryo-EM structure shows it directly, and the same term is carried by beta-actin and, by IDA, by budding-yeast ARP1. Reason: GOA currently gives human ACTR1A only two molecular-function rows: a fission-yeast-derived cortical-anchor IBA and a bare protein binding IPI. The UniProt entry fetched the same day still cross-references GO:0005200 structural constituent of cytoskeleton as IBA:GO_Central, and QuickGO returns zero hits for that term on P61163. The UniProt DR GO block is a divergent snapshot rather than a one-way record of loss - it also lacks GO:0030473, GO:0106006 and GO:0005515, which GOA does have - so the mismatch on its own would be consistent with a stale cross-reference block, and the load-bearing evidence is the QuickGO queries rather than the DR lines. It should be reinstated on stronger evidence than before: the human dynactin structure models eight ACTR1A protomers forming the two-protofilament backbone, joined through the surface actin itself uses to polymerise, and the complex has an exactly defined length that depends on that polymer. This is the same annotation pattern GO uses for structural constituent of ribosome, it is carried by ACTB itself, and S. cerevisiae ARP1 carries it by IDA. The qualifier follows GOA precedent in this family, where both yeast ARP1 and human ACTR10 use enables. Most pointedly, ACTR10/Arp11 - the single-copy subunit whose job is to cap and terminate the filament - does carry GO:0005200 by IBA while ACTR1A, present in eight copies and actually forming it, does not. Supporting Evidence: PMID:40186871 we purified dynactin from human cell culture and solved the first cryo-EM structure of human dynactin PMID:25814576 The shoulder and ERs recruit eight Arp1s and stabilize their polymerization into a structure with 5 subunits on the top protofilament and three on the bottom. PMID:25814576 Together with CapZαβ binding to the barbed end this results in a highly stable complex of an exactly defined length. PMID:7518465 Antibodies to the actin-related protein Arp1 (previously referred to as actin-RPV), bound at various sites along the filament, demonstrating that this protein assembles in a polymer similar to conventional actin. file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md ACTR1A protomers modelled: **8** (chains A, B, C, D, E, F, G, I); the modelled sequence is 100.0% identical to UniProt P61163. file:human/ACTR1A/ACTR1A-uniprot.txt DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central. |
| GO:0043531 ADP binding | IDA PMID:40186871 The Chlamydia effector Dre1 binds dynactin to reposition hos... | NEW | Summary: ADP is modelled in all eight ACTR1A protomers of the human dynactin structure, in the conserved actin nucleotide cleft. ACTR1A currently has no nucleotide-binding annotation of any kind because GOA retired the UniProt-keyword pipeline that supplied it. Reason: The UniProt entry still cross-references GO:0005524 ATP binding as IEA:UniProtKB-KW, but QuickGO returns zero human annotations for GO_REF:0000043, so that whole route is gone; human ACTB has likewise lost ATP binding, and a QuickGO query for GO:0000166 with goUsage=descendants returns zero hits for each of ACTB, ACTR1A, ACTR1B and ACTR10, so no nucleotide-binding function of any granularity survives anywhere in the human actin/Arp set. The nucleotide site is not hypothetical. Computing the ATP contacts of beta-actin from PDB 2BTF and transferring them by alignment, ACTR1A retains 19 of 25 (ACTR1B 20/25, while the capping paralog ACTR10 retains only 10/25 and loses actin's D157/G158 phosphate pair); and in the human dynactin structure ADP is modelled in 8 of 8 ACTR1A chains, with 20 of the 22 nucleotide-contacting positions coinciding with beta-actin's own ATP contacts. I propose the term for the ligand actually observed rather than GO:0005524, because ATP binding for Arp1 is still only a sequence-based prediction and no structure has resolved an ATP-bound Arp1; the nucleotide here behaves as a structural cofactor of the actin fold, not as a substrate for chemical work, and no ATPase activity has been demonstrated for Arp1. The evidence is the deposition, not the prose: the ADP is present in the deposited coordinates of PDB 9B85 and 9B7J - named in supporting_entities so a downstream curator does not search the text of PMID:40186871 for it and fail to find it - but is nowhere discussed in that paper. Supporting Evidence: file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md ACTR1A chains with a modelled nucleotide: **8/8**, ligand(s) ADP. file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md align onto residues that contact ATP in 2BTF beta-actin, i.e. the ACTR1A nucleotide sits in the conserved actin nucleotide cleft. file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md source organism *Bos taurus*, 99.7% identical to human ACTB over the modelled region file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md | ACTR1A | 53.1 | 25 | 19 | 76.0 | file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md | ACTR10 | 28.0 | 25 | 10 | 40.0 | PMID:25814576 Both consist of four subdomains surrounding a nucleotide binding site (fig. S4). PMID:10074429 on the basis of conserved sequence features, is predicted to bind ATP and possibly polymerize file:human/ACTR1A/ACTR1A-uniprot.txt DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. |
| GO:0045504 dynein heavy chain binding | ISS PMID:25814576 The structure of the dynactin complex and its interaction wi... | NEW | Summary: The dynein heavy-chain tails dock directly on the Arp1 filament, in clefts formed between adjacent Arp1 protomers. This is the interaction the filament exists to provide, and GOA records no dynein-binding function for any part of dynactin's filament. Reason: Cryo-EM of the dynein-tail/dynactin/BICD2N complex shows the dynein tail bound directly to the Arp1 filament, at sites equivalent to the myosin-binding site on actin, and the filament's length and translational symmetry are what force dynein into its active conformation - so this is ACTR1A's central interaction, not an incidental one. The qualifier is contributes_to rather than enables because each docking site is a cleft between two protomers (Arp1-D with Arp1-F, Arp1-F with beta-actin-H, Arp1-A with Arp1-C), so no single ACTR1A molecule presents the site. Evidence is ISS because the structure used native dynactin purified from pig brain; the supporting entity is pig ACTR1A (F2Z5G5), whose sequence and filament geometry match the human structure. Supporting Evidence: PMID:25814576 The dynein tail binds directly to the Arp1 filament PMID:25814576 They bind adjacent clefts between Arp1-D & F (chain-1) and Arp1-F & β-actin-H (chain-2) (Fig. 5F,G). PMID:25814576 the filament length provides additional binding sites that force dynein to adopt its active conformation PMID:36071160 Cryo-electron microscopy (cryo-EM) showed how their coiled-coils run along dynactin’s filament, positioning dynein in a conformation that relieves its intrinsic inhibition |
| GO:0051258 protein polymerization | IDA PMID:40186871 The Chlamydia effector Dre1 binds dynactin to reposition hos... | NEW | Summary: ACTR1A self-associates into a polymer, using actin's own longitudinal interface. The generic polymerization term is the right one; GO:0030041 actin filament polymerization would be wrong. Reason: In the human dynactin structure the ACTR1A-ACTR1A interfaces split cleanly by size into six large intra-protofilament contacts and a set of smaller lateral ones, and all six large interfaces share ACTR1A residues 44-49, 51, 52, 65-68, 205, 213 and 243-246 - so this is a property of the filament, not of one hand-picked chain pair. In beta-actin numbering the subdomain-2 members of that consensus are 40-45, 47, 48 and 61-64, i.e. actin's DNase-I-binding loop, the canonical longitudinal polymerisation contact; the remainder (beta-actin 200, 208, 242-245) are subdomain-3/4 contacts on the partner face, reported in full in RESULTS.md rather than omitted. So ACTR1A polymerises with actin's own machinery rather than a repurposed surface, and purified native Arp1 polymerises on its own in vitro. GO:0030041 actin filament polymerization is nonetheless inappropriate: its definition requires assembly of actin filaments by addition of actin monomers, whereas the polymer here is an Arp1 mini-filament of eight Arp1 plus one beta-actin, and the monomers added are Arp1. On the choice of reference: a static structure is used as the direct assay because what it resolves is the product of the process in human material - eight protomers in the polymerised state, joined through the canonical longitudinal interface, at defined stoichiometry - whereas the kinetic demonstration that Arp1 polymerises (PMID:10074429) was performed on purified native Arp1 whose species the abstract does not state, so it is cited as corroboration rather than as the primary reference for a human annotation. If a curator prefers process-kinetic evidence the honest pairing would be ISS on PMID:10074429 once its source species is confirmed from the full text. For the same reason no actin-filament dynamics, severing, treadmilling or depolymerisation term should be applied: the dynactin filament is of exactly defined length, doubly capped and non-dynamic, and even free Arp1 polymers never reach conventional actin-filament lengths. Supporting Evidence: file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md splitting the ACTR1A-ACTR1A interfaces at the largest gap in their contact counts separates 6 large (>= 230 atom contacts, intra-protofilament) interfaces from the smaller lateral ones file:human/ACTR1A/ACTR1A-bioinformatics/RESULTS.md Positions present in **every** large interface: 44, 45, 46, 47, 48, 49, 51, 52, 65, 66, 67, 68, 205, 213, 243, 244, 245, 246. In beta-actin numbering, those below residue 70 (subdomain 2) are [40, 41, 42, 43, 44, 45, 47, 48, 61, 62, 63, 64] and the rest are [200, 208, 242, 243, 244, 245]. PMID:10074429 Arp1 was found to polymerize rapidly into short filaments that were similar, but not identical, in length to those in dynactin. PMID:10074429 With time, these filaments appeared to anneal to form longer assemblies but never attained the length of conventional actin filaments. PMID:25814576 What makes the filament in dynactin short and defined, when purified Arp1 filaments vary in length (18)? PMID:7518465 The dynactin complex visualized by deepetch electron microscopy appears as a short filament 37-nm in length, which resembles F-actin |
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Download this section (compressed HTML)Q: Within one PANTHER family, GO:0005200 structural constituent of cytoskeleton has been given by IBA (qualifier 'enables') to ACTR10/Arp11, the single-copy subunit whose structural role is to cap and terminate the Arp1 mini-filament, while ACTR1A - present in eight copies and actually forming that filament - has no GO:0005200 annotation at all, even though UniProt still cross-references one for it and budding-yeast ARP1 carries it by IDA. Has the assignment been inverted between the two paralogs?
Suggested experts: Schroer TA, Carter AP
Q: Retiring the UniProt-keyword pipeline (GO_REF:0000043) removed ATP binding from ACTR1A and from every other human protein, including beta-actin itself, which nonetheless retains GO:0016887 ATP hydrolysis activity. Should GOA replace the actin family's nucleotide-binding annotations by another route, given that human structures now model the nucleotide in all eight Arp1 protomers of dynactin?
Q: ComplexPortal has annotated pig ACTR1A, DCTN1, DCTN2, DCTN4, DCTN5, CAPZA1 and CAPZB to GO:0030989 dynein-driven meiotic oscillatory nuclear movement with evidence IDA, citing PMID:36071160 - a cryo-EM structure of dynein-dynactin on microtubules. The term is defined around an astral array emanating from a spindle pole body. These rows have been propagated to rat by ISO and are the only mammalian support behind human ACTR1A's GO:0030473 IBA. Should they be withdrawn?
Suggested experts: Carter AP, Chaaban S
Q: Is GO:0106006 cytoskeletal protein-membrane anchor activity appropriate for any mammalian dynactin subunit? In human mitosis the cortical membrane link is supplied by Galphai-LGN-NuMA and LGN is required for cortical dynein-dynactin, so dynactin looks like the anchored partner rather than the anchor.
Q: Do ACTR1A and ACTR1B have distinguishable functions, or is ACTR1B simply a minor variant subunit? Both are dynactin subunits with comparable mRNA distribution, yet they occur in the complex at about 15:1 in favour of ACTR1A, and every filament position in the human dynactin structure is assigned to ACTR1A. Is there any dynactin population, cell type or cargo for which ACTR1B incorporation matters?
Suggested experts: Schroer TA
Q: Is the reported ACTR1A requirement for TLR2-driven cytokine induction a direct signalling role or an indirect consequence of dynactin-dependent receptor trafficking? It rests on one study combining cross-linking proteomics with knockdown.
Q: SETD3 methylates ACTR1A in vitro. Is ACTR1A methylated in cells, at which histidine, and does the modification affect polymerisation or dynein activation?
Experiment: Measure nucleotide binding and turnover directly on purified recombinant human ACTR1A - filter binding or fluorescent-nucleotide exchange with ATP versus ADP, plus a malachite-green hydrolysis assay - to settle whether the correct molecular function is ATP binding, ADP binding, or both, and whether Arp1 is an ATPase at all.
Hypothesis: ACTR1A binds ATP at the retained actin cleft and hydrolyses it during or after incorporation into the dynactin filament, leaving the ADP state seen in the assembled complex.
Type: biochemistry (nucleotide binding and hydrolysis assays)
Experiment: Replace endogenous ACTR1A with a degron-tagged allele and follow minus-end-directed cargo transport, Golgi positioning and mitotic spindle orientation after acute depletion. This would give a human loss-of-function annotation at native expression levels, rather than relying on p50/dynamitin overexpression, which disperses the entire complex.
Hypothesis: ACTR1A is required, at endogenous levels, for dynein-driven minus-end cargo transport, Golgi positioning and mitotic spindle orientation in human cells.
Type: acute degron depletion with live-cell imaging
Experiment: Mutate the ACTR1A subdomain-2 loop identified here as the longitudinal polymerisation interface (residues 42-52) and ask, by cryo-EM and in vitro reconstitution, whether a shorter or non-polymerising filament still recruits the dynein tail and still activates processive motility - separating the structural-constituent function from the dynein-binding function.
Hypothesis: The structural-constituent function of ACTR1A (polymerisation into a defined-length filament) is separable from its dynein-heavy-chain-binding function.
Type: structure-guided mutagenesis with in vitro reconstitution
Experiment: Test the anchoring question directly in human cells: tether dynactin to the plasma membrane optogenetically in LGN- and NuMA-depleted cells and ask whether cortical microtubule capture is restored. A positive result would justify GO:0106006 for mammalian dynactin; a negative one would justify removing it.
Hypothesis: Mammalian dynactin does not itself supply a cytoskeleton-to-membrane anchoring activity; the cortical anchor is Galphai-LGN-NuMA and dynactin is the anchored partner.
Type: optogenetic cortical tethering in depleted cells
Experiment: Tag ACTR1A and ACTR1B at their endogenous loci with distinguishable tags and quantify their incorporation into dynactin across cell types, then test whether ACTR1B-containing complexes differ in cargo selectivity - the paralog question has been open since the isoforms were separated in 1994.
Hypothesis: ACTR1B incorporation into dynactin is functionally consequential rather than incidental, and defines a minor dynactin population with distinct cargo selectivity.
Type: endogenous dual tagging with quantitative proteomics
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