ACTR1B encodes beta-centractin (Arp1B), one of two human actin-related protein 1 paralogs and a subunit of dynactin, the multiprotein cofactor that activates cytoplasmic dynein for long-range transport towards microtubule minus ends. Dynactin is built around a short, actin-like filament of eight Arp1 protomers plus one conventional actin, capped at the barbed end by capping protein and at the pointed end by Arp10/Arp11 with the p62-p25-p27 complex; this filament is the structural core on which the p150Glued-containing shoulder and the cargo-adaptor binding sites are assembled. Beta-centractin is 91 per cent identical to alpha-centractin and co-assembles with it into the same filament, but as a minor component: subcellular fractionation with isoform-specific antibodies places both isoforms entirely within the cytosolic 20S dynactin complex, with no free pool of either, at a constant ratio of roughly fifteen alpha to one beta. Both paralogs are ubiquitously expressed without tissue restriction -- it is a third, gamma-centractin mRNA species that is tissue-specific -- but beta is the minor of the two by protein abundance. Through dynactin, beta-centractin participates in dynein-dependent movement of vesicles and organelles, endosome and lysosome positioning, Golgi organisation and nuclear positioning, and the complex is found in the cytosol and at the centrosome. The Arp1 filament differs from conventional actin in being a fixed-length, non-dynamic polymer whose length is set by other dynactin subunits rather than by treadmilling, and its protomers each bind a nucleotide. No function has been demonstrated for beta-centractin outside dynactin, and no phenotype has been reported for its loss alone.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030473 nuclear migration along microtubule | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dynein-dynactin does drive nuclear movement along microtubules, and this is the one propagated biological process on the record whose donors carry real experimental evidence for it. The strongest donor is the Aspergillus nidulans entry, whose IMP comes from the paper that cloned nudK and identified it as Arp1, giving the first evidence that dynactin acts in nuclear migration; the S. pombe donor adds IMP evidence for the meiotic descendant term. Human ACTR1A holds the identical IBA from the identical donor set, so this is a family-level term shared by both centractins rather than a transfer between them. Kept as non-core because nuclear migration is one downstream instance among many dynactin-dependent transport processes, and because ACTR1B is a sub-stoichiometric protomer of the filament rather than a dedicated nuclear-migration factor. Reason: Term is correct in kind and its donors are experimentally supported in two fungi, but it names a single downstream process of the complex ACTR1B belongs to, not ACTR1B's core role. No human experimental evidence exists for either centractin paralog here. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000233666 · PANTHER tree node (pan-eukaryotic Arp1/centractin clade) UNRESOLVED PANTHER tree node, not a protein: cannot itself carry evidence. PomBase:SPBC1347.12 · arp1, S. pombe (O94630, Swiss-Prot) SUPPORTS TRANSFER Carries IMP + NAS (PMID:25736293) for the descendant GO:0030989, so it has its own experimental evidence under this term. UniProtKB:F2Z5G5 · ACTR1A, Sus scrofa (alpha-centractin, Swiss-Prot) SOURCE BAD Its only experimental annotation under GO:0030473 is a ComplexPortal IDA to the descendant GO:0030989 from PMID:36071160 -- a reconstituted dynein-dynactin-BICDR1 motility/structure paper. GO:0030989 is defined by movement led from a spindle pole body during meiosis I, which pig cells do not have; that donor row looks wrong. It does not undermine the organism-neutral parent term. UniProtKB:Q5BBX7 · ANIA_01953 / AN1953, Aspergillus nidulans SUPPORTS TRANSFER UNREVIEWED (TrEMBL) and named 'Uncharacterized protein', so its name is not evidence of function -- but its annotations are: it carries GO:0030473 by IMP (PMID:10467007, which identified nudK as Arp1). 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. |
| GO:0106006 cytoskeletal protein-membrane anchor activity | IBA GO_REF:0000033 | MODIFY | Summary: This is the substantive defect on the record, and it affects ACTR1A identically. GO:0106006 is defined as the binding activity of a molecule that brings together a cytoskeletal protein or complex and a plasma membrane lipid or membrane-associated protein in order to maintain the cytoskeleton at a specific cortical membrane location. Three checks argue that this is the wrong activity for Arp1. First, the node is narrow and single-sourced: QuickGO shows GO:0106006 IBA reaches only five human proteins, and PTN007551901 delivers it to exactly ACTR1A and ACTR1B from one S. pombe donor. Second, that donor's own experiment shows a process requirement, not a bridging activity -- the cortical receptor Num1/Mcp5 binds dynein independently of dynactin, and what the dynactin subunits were shown to do was regulate microtubule shrinkage and bundling, in fission-yeast meiotic prophase. Third, Arp1 does have a documented membrane-skeleton partner, Golgi-associated betaIII spectrin, but that recruits dynactin to intracellular membranes, not to a cortical membrane location, so the term's differentia fails. What Arp1 demonstrably contributes is the backbone filament that the rest of dynactin is built on, which is the definition of protein complex scaffold activity. Reason: Two candidate structural MFs fit Arp1, and GO:0005200 structural constituent of cytoskeleton is listed first on precedent. It is the term conventional beta-actin itself carries; S. cerevisiae ARP1 holds it by its own IDA (PMID:9658168); ACTR10/Arp11, the capping subunit of the very same filament, already holds it by IBA with the enables qualifier; and it is what this PANTHER family previously propagated to the human centractins, as UniProt's cross-reference block for P42025 still shows even though it is absent from current GOA for both paralogs. It is also not a category error to call dynactin a cytoskeletal structure: GO's own ancestor list places GO:0005869 under GO:0015629 actin cytoskeleton. GO:0140378 protein complex scaffold activity is given as the second option because its definition names the role more exactly -- 'a structural molecule activity of a protein-containing complex component that serves to hold the complex together' is verbatim the role UniProt records for the fungal Arp1 donors, that Arp1 forms the backbone filament of the dynactin rod and serves as the scaffold for the remaining subunits -- but it has no precedent in this family. Either is a large improvement on GO:0106006, which requires a bridge to a plasma membrane component holding the cytoskeleton at a cortical location, something no Arp1 experiment supports in any organism. Two notes for whoever applies this. (i) The qualifier should become 'enables' rather than 'contributes_to', because a structural constituent role is the subunit's own activity, and that is the qualifier ACTR10 already carries for GO:0005200. (ii) Because the term arrives at both paralogs from the same PANTHER node, fixing it at PTN007551901 fixes ACTR1A and ACTR1B in one edit. The parallel, independent review of ACTR1A converged on GO:0005200 as the term to restore, which is corroboration rather than coordination -- so PAINT should receive one recommendation, not two competing ones. ACTR1B's spectrin binding is itself untested, so 'spectrin binding' is deliberately NOT proposed here. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN007551901 · PANTHER tree node UNRESOLVED PANTHER tree node, not a protein. QuickGO shows GO:0106006 IBA reaches only ACTR1A and ACTR1B from this node, so it is the centractin node and the whole human annotation rests on the single S. pombe donor. PomBase:SPBC1347.12 · arp1, S. pombe (O94630, Swiss-Prot) SUPPORTS SOURCE BUT NOT TARGET The sole experimental donor: EXP from PMID:25736293. That paper shows the pombe dynactin subunits are required for cortical dynein anchoring during meiotic prophase, while Num1/Mcp5 binds dynein independently of dynactin and the measured dynactin contribution was microtubule shrinkage/bundling. Sound for pombe as a process requirement; it does not establish a membrane-bridging binding activity that can propagate as an MF. Proposed replacements: structural constituent of cytoskeleton protein complex scaffold activity Supporting Evidence: PMID:25736293 Cortical factor Num1 (also known as Mcp5), which was also required for dynein anchoring, bound to dynein independently of dynactin. PMID:25736293 Whereas Num1 suppressed the sliding of dynein foci along the cortex, Arp1, Mug5 and Jnm1 were involved in the regulation of shrinkage and bundling of microtubules. PMID:11461920 Here, we demonstrate that Arp1 binds directly to the Golgi-associated betaIII spectrin isoform. PMID:11461920 We hypothesize that the interaction between betaIII spectrin and Arp1 recruits dynein and dynactin to intracellular membranes and provides a direct link between the microtubule motor complex and its membrane-bounded cargo. PMID:40186871 Dynactin binds MTs anchored at the GA as well as to βIII spectrin on GA membranes through its Arp1 subunit. file:human/ACTR1B/ACTR1B-uniprot.txt DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central. |
| GO:0005869 dynactin complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct, and every resolvable donor carries its own experimental evidence for dynactin membership: S. pombe arp1 by IPI with Jnm1, S. cerevisiae ARP1 by IDA and IPI, pig ACTR1A by IPI from the dynactin cryo-EM work, and C. elegans arp-1 by IDA. The one caveat is bookkeeping rather than biology -- the WormBase token maps to two unreviewed accessions and only one of them, Q9NA98, has any annotations. This row is also redundant with, and weaker than, the direct human evidence on the PMID:7696711 row below, where isoform-specific antibodies placed beta-centractin itself in the 20S complex. Reason: Dynactin membership is the core fact about ACTR1B and this propagation is sound at every donor. Accepted despite being redundant with the stronger direct human row, because an IBA from five independently-annotated orthologues is itself informative. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000233666 · PANTHER tree node (pan-eukaryotic Arp1/centractin clade) UNRESOLVED PANTHER tree node, not a protein: cannot itself carry evidence. PomBase:SPBC1347.12 · arp1, S. pombe (O94630, Swiss-Prot) SUPPORTS TRANSFER Carries GO:0005869 by IPI with Jnm1/SPCC11E10.03 (PMID:25736293). SGD:S000001171 · ARP1/ACT5, S. cerevisiae (P38696, Swiss-Prot) SUPPORTS TRANSFER Carries GO:0005869 by IDA (PMID:9658168) and IPI (PMID:18245366), and also holds GO:0005200 structural constituent of cytoskeleton by its own IDA. UniProtKB:F2Z5G5 · ACTR1A, Sus scrofa (alpha-centractin, Swiss-Prot) SUPPORTS TRANSFER Carries GO:0005869 by IPI (PMID:33734450, the dynactin shoulder/pointed-end cryo-EM study). Ortholog of ACTR1A, i.e. a paralog of ACTR1B -- legitimate for IBA, but it means no ACTR1B-ortholog-strength inference is available on this row. WB:WBGene00013168 · arp-1 / Y53F4B.22, C. elegans SUPPORTS TRANSFER Q9NA98 carries GO:0005869 by IDA (PMID:20964796). Unreviewed, so its 'Actin' name is not used as evidence. 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:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Keyword-mapped from UniProt's own subcellular location statement, which places beta-centractin in the cytoplasm and cytoskeleton and specifically at the microtubule organizing center and centrosome; UniProt's FUNCTION line likewise states the complex is associated with the centrosome. Independently supported by the IDA row from centrosome proteomics below, and by ACTR1A carrying the same pair. Dynactin at the pericentriolar material is well established. Reason: Correct and independently corroborated by an IDA on the same term; the SubCell mapping faithfully reflects the curated UniProt location. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: True but strictly redundant: GO:0005813 centrosome, which ACTR1B holds by IDA, is a descendant of GO:0005815 microtubule organizing center, so this ARBA-derived parent adds no information beyond the annotation it sits above. Reason: Not wrong -- an uninformative ancestor of an annotation already present at greater specificity with experimental evidence. Retained as non-core rather than removed. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00029135 · ARBA machine-learning rule CIRCULAR OR REDUNDANT Rule output, not a gene product. The term it delivers is an ancestor of the GO:0005813 IDA the same protein already carries. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: True but strictly redundant. The QuickGO ancestor list for GO:0005869 dynactin complex contains GO:0005856 cytoskeleton (along with GO:0015629 actin cytoskeleton and GO:0005875 microtubule associated complex), so this term is an ancestor of an annotation ACTR1B already has with better evidence. Incidentally, that placement of dynactin under the actin cytoskeleton is also why a structural-constituent-of- cytoskeleton framing for Arp1 is not a category error. Reason: Correct but uninformative ancestor of the dynactin complex annotation; retained as non-core. |
| GO:0005515 protein binding | IPI PMID:12857853 Interactions between the evolutionarily conserved, actin-rel... | KEEP AS NON CORE | Summary: IntAct records this pair from a density-sedimentation experiment with both partners detected by western blot as neutral components, i.e. cytosolic beta-centractin co-sediments with p150Glued in the 20S complex. That is co-membership in dynactin, not a direct contact -- p150 is housed in the dynactin shoulder and reaches the filament through the four p50/DCTN2 subunits, and DCTN1 is not even modelled in the human dynactin cryo-EM structure. Bare protein binding therefore adds nothing beyond the part_of GO:0005869 annotation, which states the same fact informatively. Reason: The partner is real and the experiment is real, so this is not over-annotation; but protein binding conveys no function, and the evidence is co-sedimentation rather than a demonstrated direct interface. Kept as non-core; the informative encoding is the dynactin complex term. Supporting Evidence: PMID:33734450 The unique architecture of the shoulder securely houses the p150 subunit and positions the four identical p50 subunits in different conformations to bind dynactin's filament. |
| GO:0005515 protein binding | IPI PMID:12857853 Interactions between the evolutionarily conserved, actin-rel... | KEEP AS NON CORE | Summary: A different experiment in the same paper: IntAct records this pair as a pull down, matching the reported coprecipitation of recombinant Arp11 and Arp1. The partner is mouse Actr10/Arp11, which UniProt flags as Xeno, and Arp11 is the genuine pointed-end cap of the Arp1 mini-filament, so this is a real and mechanistically meaningful dynactin-internal contact. Note that GOA's seeding collapses the two PMID:12857853 rows into one; they are separate experiments with separate partners and are reviewed separately here. One limit I could not close: the cached full text lacks the Materials and Methods, so which Arp1 paralog was used in the coprecipitation cannot be checked from the cache. The IntAct curator, who read the full text, assigned P42025. Reason: Genuine, direct, dynactin-internal interaction with the pointed-end capping Arp, but expressed through an uninformative term. Not downgraded further: per project policy an experimental annotation is not second-guessed on the basis of a full text I cannot read. Supporting Evidence: PMID:12857853 but Arp1 has a vanishingly low critical concentration for polymerization |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: Proximity-dependent biotinylation at the centrosome-cilium interface reporting ACTR1B near DCTN1. Consistent with dynactin co-membership and with the centrosome localisation on this record, but BioID reports proximity rather than contact, and the term is uninformative. Reason: Real partner, real screen, corroborates dynactin co-membership and centrosomal localisation; but proximity labelling plus a bare binding term is not a function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: The only non-dynactin partner among the five protein-binding rows, and the weakest. UniProt reports NbExp=3 for the ACTR1B-HTT pair, which reads like triplicate independent support, but all three IntAct records -- two hybrid array, two hybrid pooling and validated two hybrid -- come from PMID:32814053 alone, a single systematic yeast two-hybrid screen of neurodegeneration-associated proteins. Three Y2H formats in one study are not independent replication. Huntingtin's documented route to dynactin in the literature is indirect, via HAP1 to p150Glued, not via the Arp1 filament, and no orthogonal assay places HTT on Arp1. Reason: Unreplicated yeast two-hybrid hit from a disease-focused screen, presented by UniProt's NbExp count as if it were three independent experiments when all three records share one publication. Not removed -- Y2H is an experimental assay and HTT is a plausible dynactin-pathway protein -- but it should not stand as an ACTR1B molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 affinity-purification mass spectrometry. Taken together with the rest of that dataset this is the strongest modern evidence that ACTR1B is in assembled dynactin: IntAct returns ACTR1B partnered with DCTN1 through DCTN6, CAPZA1, CAPZA2, CAPZB, ACTR10 and ACTR1A itself, i.e. both filament ends, the shoulder and the pointed-end complex. The co-purification with ACTR1A in particular shows the two paralogs occupy the same filament rather than separate alpha-only and beta-only dynactins. All of that content belongs in the complex annotation, not in a bare binding term. Reason: Real co-complex partner from a high-quality AP-MS network; the biologically informative statement is dynactin membership, which is separately annotated. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | REMOVE | Summary: Topologically impossible for a cytosolic actin-fold protein. This extracellular region assertion comes from the Reactome Neutrophil degranulation pathway, where ACTR1B is modelled as a granule lumen protein released by exocytosis. The Reactome pathway model places ACTR1B among the neutrophil granule lumen proteins, membership that traces to granule subcellular-fraction proteomics (Reactome's own summation for these reactions cites Rorvig et al. 2009, 2013). ACTR1B has no signal peptide and no transmembrane segment -- the P42025 feature table contains only CHAIN, MOD_RES and VARIANT -- and UniProt places it in the cytoplasm and cytoskeleton only, with the founding paper finding no free pool outside dynactin. A cytosolic actin-fold protein cannot be topologically inside a granule lumen or secreted. The decisive argument is the paralog pair: ACTR1A is in the same complex at roughly fifteen times the abundance, so if beta-centractin were genuinely granule-lumen cargo alpha-centractin would necessarily be too, and ACTR1A carries none of these four Reactome annotations. The asymmetry is detection stochasticity in a granule proteome, not localisation. If the proteomic observation is worth recording at all, the honest representation is a granule-associated cytoplasmic-face location or the extracellular-vesicle row already on this record, not a lumen or extracellular term. Reason: Pathway-model-derived location that contradicts the protein's topology: no signal peptide, no transmembrane segment, curated location is cytoplasm and cytoskeleton, no free pool outside dynactin. The paralog test settles it: ACTR1A, fifteen times more abundant in the same complex, carries none of these annotations, so the beta-only pattern reflects granule-proteome detection stochasticity rather than localisation. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: Reactome:R-HSA-6798748 · Reactome reaction (Neutrophil degranulation) SOURCE BAD Pathway model, not a gene product. It places ACTR1B in the granule lumen compartment on the strength of granule-fraction proteomics; the compartment assignment does not hold for a cytosolic protein. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, 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:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | REMOVE | Summary: Topologically impossible for a cytosolic actin-fold protein. This extracellular region assertion comes from the Reactome Neutrophil degranulation pathway, where ACTR1B is modelled as a granule lumen protein released by exocytosis. The Reactome pathway model places ACTR1B among the neutrophil granule lumen proteins, membership that traces to granule subcellular-fraction proteomics (Reactome's own summation for these reactions cites Rorvig et al. 2009, 2013). ACTR1B has no signal peptide and no transmembrane segment -- the P42025 feature table contains only CHAIN, MOD_RES and VARIANT -- and UniProt places it in the cytoplasm and cytoskeleton only, with the founding paper finding no free pool outside dynactin. A cytosolic actin-fold protein cannot be topologically inside a granule lumen or secreted. The decisive argument is the paralog pair: ACTR1A is in the same complex at roughly fifteen times the abundance, so if beta-centractin were genuinely granule-lumen cargo alpha-centractin would necessarily be too, and ACTR1A carries none of these four Reactome annotations. The asymmetry is detection stochasticity in a granule proteome, not localisation. If the proteomic observation is worth recording at all, the honest representation is a granule-associated cytoplasmic-face location or the extracellular-vesicle row already on this record, not a lumen or extracellular term. Reason: Pathway-model-derived location that contradicts the protein's topology: no signal peptide, no transmembrane segment, curated location is cytoplasm and cytoskeleton, no free pool outside dynactin. The paralog test settles it: ACTR1A, fifteen times more abundant in the same complex, carries none of these annotations, so the beta-only pattern reflects granule-proteome detection stochasticity rather than localisation. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: Reactome:R-HSA-6800434 · Reactome reaction (Neutrophil degranulation) SOURCE BAD Pathway model, not a gene product. It places ACTR1B in the granule lumen compartment on the strength of granule-fraction proteomics; the compartment assignment does not hold for a cytosolic protein. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, 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:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | REMOVE | Summary: Topologically impossible for a cytosolic actin-fold protein. This secretory granule lumen assertion comes from the Reactome Neutrophil degranulation pathway, where ACTR1B is modelled as a granule lumen protein released by exocytosis. The Reactome pathway model places ACTR1B among the neutrophil granule lumen proteins, membership that traces to granule subcellular-fraction proteomics (Reactome's own summation for these reactions cites Rorvig et al. 2009, 2013). ACTR1B has no signal peptide and no transmembrane segment -- the P42025 feature table contains only CHAIN, MOD_RES and VARIANT -- and UniProt places it in the cytoplasm and cytoskeleton only, with the founding paper finding no free pool outside dynactin. A cytosolic actin-fold protein cannot be topologically inside a granule lumen or secreted. The decisive argument is the paralog pair: ACTR1A is in the same complex at roughly fifteen times the abundance, so if beta-centractin were genuinely granule-lumen cargo alpha-centractin would necessarily be too, and ACTR1A carries none of these four Reactome annotations. The asymmetry is detection stochasticity in a granule proteome, not localisation. If the proteomic observation is worth recording at all, the honest representation is a granule-associated cytoplasmic-face location or the extracellular-vesicle row already on this record, not a lumen or extracellular term. Reason: Pathway-model-derived location that contradicts the protein's topology: no signal peptide, no transmembrane segment, curated location is cytoplasm and cytoskeleton, no free pool outside dynactin. The paralog test settles it: ACTR1A, fifteen times more abundant in the same complex, carries none of these annotations, so the beta-only pattern reflects granule-proteome detection stochasticity rather than localisation. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: Reactome:R-HSA-6798748 · Reactome reaction (Neutrophil degranulation) SOURCE BAD Pathway model, not a gene product. It places ACTR1B in the granule lumen compartment on the strength of granule-fraction proteomics; the compartment assignment does not hold for a cytosolic protein. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, 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:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | REMOVE | Summary: Topologically impossible for a cytosolic actin-fold protein. This ficolin-1-rich granule lumen assertion comes from the Reactome Neutrophil degranulation pathway, where ACTR1B is modelled as a granule lumen protein released by exocytosis. The Reactome pathway model places ACTR1B among the neutrophil granule lumen proteins, membership that traces to granule subcellular-fraction proteomics (Reactome's own summation for these reactions cites Rorvig et al. 2009, 2013). ACTR1B has no signal peptide and no transmembrane segment -- the P42025 feature table contains only CHAIN, MOD_RES and VARIANT -- and UniProt places it in the cytoplasm and cytoskeleton only, with the founding paper finding no free pool outside dynactin. A cytosolic actin-fold protein cannot be topologically inside a granule lumen or secreted. The decisive argument is the paralog pair: ACTR1A is in the same complex at roughly fifteen times the abundance, so if beta-centractin were genuinely granule-lumen cargo alpha-centractin would necessarily be too, and ACTR1A carries none of these four Reactome annotations. The asymmetry is detection stochasticity in a granule proteome, not localisation. If the proteomic observation is worth recording at all, the honest representation is a granule-associated cytoplasmic-face location or the extracellular-vesicle row already on this record, not a lumen or extracellular term. Reason: Pathway-model-derived location that contradicts the protein's topology: no signal peptide, no transmembrane segment, curated location is cytoplasm and cytoskeleton, no free pool outside dynactin. The paralog test settles it: ACTR1A, fifteen times more abundant in the same complex, carries none of these annotations, so the beta-only pattern reflects granule-proteome detection stochasticity rather than localisation. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: Reactome:R-HSA-6800434 · Reactome reaction (Neutrophil degranulation) SOURCE BAD Pathway model, not a gene product. It places ACTR1B in the granule lumen compartment on the strength of granule-fraction proteomics; the compartment assignment does not hold for a cytosolic protein. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, 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: Detected in a shotgun proteome of exosomes from expressed prostatic secretions in urine, a preparation in which roughly 900 proteins were reported. Unlike the neutrophil-granule rows this one is on both centractin paralogs from the same dataset, so it is at least internally consistent; but abundant cytosolic cytoskeletal complexes are the archetypal co-purifiers in bulk extracellular-vesicle preparations, and there is no orthogonal validation for ACTR1B. Reason: Single high-throughput extracellular-vesicle proteome, no orthogonal confirmation, and dynactin is a cytosolic complex. Not removed, because EV packaging of cytosolic proteins is real and the observation is reproducible across the paralog pair -- but it is not part of ACTR1B's function. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: From an NK-cell membrane-proteome survey that identified 1843 proteins and itself estimated only about 40 per cent of them to be plausible membrane proteins, describing the remainder as species that might merely be transiently associated with membranes. ACTR1B has no transmembrane segment and no lipid anchor. ACTR1A, its partner in the same complex, did not pick up this annotation, which again points to detection stochasticity rather than membrane residence. Reason: A generic membrane term from a fractionation proteome whose own authors caution that most of the list is not integral to membranes. Dynactin does work on membrane cargo, so peripheral association is not absurd, but located_in membrane overstates it. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2213248 | ACCEPT | Summary: Correct and well supported. Reactome places dynactin in the cytosol for the dynein-dependent transport of peptide-loaded MHC class II to the cell surface, and the founding beta-centractin paper found both centractin isoforms predominantly in the cytosolic fraction, entirely within the 20S dynactin complex, with no free pool. This is where ACTR1B does its work. Reason: The primary compartment for ACTR1B, backed by direct human subcellular fractionation of the isoform itself, not only by pathway inference. 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:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: From a centrosome-proteomics study that combined PCP-SILAC mass spectrometry, BAC transgeneOmics and antibody screening to define human centrosome constituents. ACTR1A received the same annotation from the same work, and dynactin at the pericentriolar material is independently established; UniProt's own FUNCTION line for beta-centractin states the complex is associated with the centrosome. Reason: Direct-assay localisation consistent with the curated UniProt location, with the keyword-derived IEA row on the same term, and with dynactin's established role at the centrosome. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- FUNCTION: Component of a multi-subunit complex involved in microtubule |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | KEEP AS NON CORE | Summary: LIFEdb GFP-fusion localisation in living cells. Correct, but cytoplasm is an ancestor of the cytosol annotation ACTR1B already carries, and the assay was on an expressed fusion protein rather than the endogenous subunit. Reason: True but uninformative parent of the cytosol row; retained as non-core rather than removed. |
| GO:0005869 dynactin complex | TAS PMID:7696711 Beta-centractin: characterization and distribution of a new ... | ACCEPT | Summary: The single most important annotation on this record, and the answer to whether ACTR1B's dynactin membership is documented or merely assumed from paralogy. It is documented, in human, with reagents built specifically to avoid the paralog: the authors raised new antibodies precisely because existing anti-alpha-centractin reagents reacted only poorly with beta-centractin, combined them with two-dimensional gels, and found both isoforms in the cytosolic 20S dynactin complex with no free pool of either, at a constant ratio of about 15:1 alpha to beta. Over the eight Arp1 protomers of a dynactin particle that implies roughly one beta protomer per second complex -- a genuinely sub-stoichiometric subunit of a hetero-oligomeric filament. Modern AP-MS agrees and adds that ACTR1B co-purifies with ACTR1A, so the paralogs share one filament rather than forming separate alpha-only and beta-only dynactins. A second, modern instance of the same methodological point closes the case: the 2025 study that solved the human dynactin structure probed its effector's binding with an **anti-Arp1b** antibody, testing Dre1 variants in co-transfection assays against p150glued, p50-dynamitin and Arp1b, and immunoblotting Strep affinity-purification eluates for Arp1b alongside p150glued, p50-dynamitin and dynein. Those two statements are Methods -- what was assayed and what was blotted -- so the result itself is carried by a third sentence: Dre1 variants predicted to disrupt the fold 'decreased binding of endogenous dynactin subunits and dynein', and a conservative F195Y replacement did not, which presupposes baseline binding of the endogenous subunits assayed. Since Arp1b is one of the three dynactin subunits in that readout and is detected with a paralog-specific antibody, endogenous beta-centractin is among the dynactin subunits recovered on Dre1: a modern, human, paralog-resolved result independent of AP-MS, thirty years after the 2D-gel work. The per-subunit bands are in Figure 2D, which the cached text does not render, so the claim is stated at exactly that strength and no further -- and note the irony that these authors chose anti-Arp1b as their Arp1-filament readout while depositing a structure that models every filament protomer as alpha. Reason: Core, and established by direct isoform-resolving experiment in human cells. One curation recommendation: the evidence code understates the evidence. PMID:7696711 is not a review being cited for a traceable statement -- it is the primary paper that generated isoform-specific antibodies and ran 2D gels on cytosolic fractions, so IDA is the appropriate code. ACTR1A's row from the same paper should be re-coded with it. Supporting Evidence: PMID:7696711 As antibodies previously raised against alpha-centractin reacted only poorly with beta-centractin, new antibodies were produced and combined with two-dimensional gel electrophoresis to discriminate the two isoforms. 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. PMID:7696711 The isoforms were found in a constant ratio of approximately 15:1 (alpha:beta) in the dynactin complex. file:human/ACTR1B/ACTR1B-deep-research-affinage.md stoichiometric minor subunit of the cytosolic 20S dynactin complex PMID:40186871 These Dre1 variants were tested in co-transfection assays for binding to multiple dynactin subunits (p150glued, p50-dynamitin [DCTN2], Arp1b) as well as to dynein PMID:40186871 Eluates were immunoblotted with anti-p150glued, anti-p50-dynamitin, anti-dynein 74 kDa, anti-Arp1b, anti-FHL2, anti-Strep, and anti-GAPDH antibodies. PMID:40186871 A single substitution in CR1, in which phenylalanine 195 was changed to proline or to alanine (F195P or F195A) and which is predicted to disrupt the strand fold, decreased binding of endogenous dynactin subunits and dynein to the transfected Dre1 variants |
| GO:0047496 vesicle transport along microtubule | IC file:human/ACTR1B/ACTR1B-uniprot.txt | NEW | Summary: Proposed to fill a genuine gap: ACTR1B's only biological process in GOA is the non-core GO:0030473 nuclear migration along microtubule, so the record carries nothing about the transport function dynactin actually exists to perform. This is inferred from curated complex membership, not from the paralog: ACTR1B's own UniProt FUNCTION line states that it is a component of a multi-subunit complex involved in microtubule-based vesicle motility, and its membership in that complex is established directly in human cells by isoform-specific antibodies plus two-dimensional gels, and independently by AP-MS recovering the full dynactin roster. Standard GO practice attributes the process of a complex to its structural subunits with involved_in. Reason: Dynactin's core biological role is dynein-dependent minus-end transport of vesicles and organelles, and ACTR1B is a documented structural subunit of dynactin. IC with GO:0005869 as the supporting entity records exactly that reasoning: the inference is from complex membership, which is experimentally established for ACTR1B itself, rather than from similarity to ACTR1A. On term choice: dynactin's cargo is heterogeneous (vesicles, organelles, nuclei, mRNA, viruses), so the parent GO:0030705 cytoskeleton-dependent intracellular transport would be the true LCA of everything dynactin moves. GO:0047496 is chosen instead because it is what the cited evidence actually states -- UniProt's FUNCTION line for P42025 specifies microtubule-based vesicle motility, and ACTR1A carries GO:0016192 vesicle-mediated transport by TAS -- and because being specific where the evidence is specific is safer than asserting a breadth no ACTR1B-cited source supports. Happy to generalise if curators prefer the LCA framing. Supporting Evidence: file:human/ACTR1B/ACTR1B-uniprot.txt CC -!- FUNCTION: Component of a multi-subunit complex involved in microtubule 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:0043531 ADP binding | ISS file:human/ACTR1B/ACTR1B-bioinformatics/RESULTS.md | NEW | Summary: Proposed restoration of a nucleotide-binding molecular function that GOA lost as collateral rather than by judgement, with the ligand corrected to the one actually observed. UniProt still records ATP binding for P42025 in its cross-reference block and still carries the ATP-binding and Nucleotide-binding keywords, but the term is absent from the current GOA download because the Swiss-Prot-keyword pipeline behind GO_REF:0000043 was retired wholesale. ADP rather than ATP is proposed because ATP binding by Arp1 has never been demonstrated: the paper that purified native Arp1 and showed it polymerises states that Arp1 'is predicted to bind ATP and possibly polymerize' on the basis of conserved sequence features. What has been observed is ADP: in the 2025 cryo-EM structure of human dynactin all eight Arp1 filament protomers are modelled with a bound ADP. Deriving the nucleotide-contact residues from that structure and testing retention in ACTR1B gives 17 of 18 identical, with no gaps, and the single difference is position 215 lysine to arginine -- where arginine is what S. pombe arp1, S. cerevisiae ARP1, C. elegans arp-1, A. nidulans AN1953 and conventional beta-actin all carry. ACTR1B holds the consensus residue and ACTR1A is the outlier, so beta-centractin's nucleotide site is intact and arguably more canonical than alpha's. The same substitution is fixed in mouse Actr1b, confirming it is a paralog feature and not human noise. Reason: A well-supported nucleotide-binding function was removed by pipeline retirement, not refuted, and restoring it as GO:0043531 ADP binding keeps the annotation to what the evidence shows. ATP binding remains a prediction for Arp1 (PMID:10074429), whereas ADP is resolved in every Arp1 protomer of PDB 9B85. ISS is the honest code: the nucleotide is seen in the ACTR1A protomers and ACTR1B's site is inferred from residue-level retention rather than measured, since ACTR1B appears in no deposited structure. The parallel, independent ACTR1A review reached the same ADP-over-ATP conclusion from the same structure, so the paralog pair should carry the same term. Two encoding notes. The ISS with/from is the sequence accession UniProtKB:P61163 alone; the structure PDB 9B85 is the evidence behind that choice and is cited as a reference rather than stuffed into with/from, where a PDB id would be unconventional. And if a curator objects even to ADP -- on the grounds that the nucleotide seen in the alpha protomers is being transferred to beta by similarity -- the fallback is the parent GO:0000166 nucleotide binding, which is still better than the current state of no nucleotide-binding MF at all. Two honesty notes on the ligand. ADP is the nucleotide resolved in 9B85, but that is a single post-hydrolysis structural state of a purified complex, so it evidences that the site is occupied by a nucleotide far more strongly than it evidences specificity for ADP over ATP; an actin-family protein would be expected to bind both, and the honest reading is 'ADP is what has been seen, ATP is what has been predicted'. And the UniProt DR line quoted in supported_by names ATP binding rather than ADP binding on purpose: it is cited as evidence that a nucleotide-binding MF was present and has been lost from GOA, not as evidence of which nucleotide is bound. Supporting Evidence: PMID:10074429 is predicted to bind ATP and possibly polymerize file:human/ACTR1B/ACTR1B-uniprot.txt DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. file:human/ACTR1B/ACTR1B-bioinformatics/RESULTS.md | P42025 | ACTR1B human (beta-centractin) -- the gene under review | 376 | 90.4 | 17/18 | 32/37 | |
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Download this section (compressed HTML)Q: Should the GO:0106006 cytoskeletal protein-membrane anchor activity annotation be moved off the centractin PANTHER node? It reaches ACTR1A and ACTR1B from PTN007551901 with a single experimental donor, S. pombe arp1 (EXP, PMID:25736293), and that paper demonstrates a requirement for cortical dynein anchoring while showing that the cortical receptor Num1 binds dynein independently of dynactin. GO:0106006 requires a bridge to a plasma-membrane component maintaining the cytoskeleton at a cortical location; the only documented Arp1-membrane-skeleton bridge is to Golgi betaIII spectrin on intracellular membranes. Replacing it with GO:0005200 structural constituent of cytoskeleton (qualifier enables) would fix both human paralogs in one edit and restore a structural molecular function they currently lack entirely. GO:0005200 is the term beta-actin carries, that S. cerevisiae ARP1 holds by IDA, and that ACTR10/Arp11 -- the capping subunit of this very filament -- already holds by IBA with enables; GO:0140378 protein complex scaffold activity is a defensible alternative with a tighter definition but no family precedent. The independent review of ACTR1A converged on the same recommendation.
Q: The GO:0005869 dynactin complex row on PMID:7696711 is coded TAS for both ACTR1B and ACTR1A, but that paper is primary research that raised isoform-specific antibodies and ran two-dimensional gels on cytosolic fractions specifically to tell the two centractins apart. Should both rows be re-coded IDA? As it stands, the strongest and most paralog-specific evidence either gene has is recorded with the weakest applicable code.
Q: Pig ACTR1A (F2Z5G5) carries GO:0030989 dynein-driven meiotic oscillatory nuclear movement by IDA, assigned by ComplexPortal from PMID:36071160, a reconstituted dynein-dynactin-BICDR1 motility and cryo-EM study. GO:0030989 is defined by oscillation led by an astral array emanating from a spindle pole body during meiosis I, a structure absent from mammals, and the cited paper assays neither meiosis nor nuclei. Since F2Z5G5 is a WITH/FROM donor on both human centractins' GO:0030473 IBA, should that donor annotation be corrected?
Q: GO:0140660 cytoskeletal motor activator activity has zero human protein annotations, yet dynactin is the textbook activator of cytoplasmic dynein and GO:0034452 dynactin binding is defined as binding a complex that activates dynein-based motor activity. Should the dynactin subunits carry GO:0140660 with contributes_to?
Q: Are the four Reactome Neutrophil degranulation annotations on ACTR1B (extracellular region twice, secretory granule lumen, ficolin-1-rich granule lumen) worth retiring pathway-wide rather than gene by gene? ACTR1B has no signal peptide or transmembrane segment and no free pool outside dynactin, and its partner in the same complex, ACTR1A, is fifteen times more abundant yet appears in none of these reactions -- so the pattern is granule-fraction carryover. The same asymmetry test could be applied systematically to other cytosolic complex subunits in that pathway.
Q: UniProt reports NbExp=3 for the ACTR1B-HTT interaction, but all three IntAct records come from one publication (PMID:32814053) as three yeast two-hybrid formats. Should NbExp distinguish independent publications from assay variants within a study, given that GO curators use it as a proxy for replication?
Experiment: Isoform-resolved dynactin composition by targeted mass spectrometry. Purify dynactin from human cells and quantify paralog-distinguishing peptides for ACTR1A and ACTR1B by parallel reaction monitoring, to test the 1994 15:1 ratio with modern accuracy and to establish whether beta occupancy is bimodal (some particles with one beta, others with none) or graded. The prediction from the ratio and the eight-protomer filament is roughly one beta per two particles.
Experiment: Does beta occupy a defined position in the filament? Reconstitute dynactin, or immunoprecipitate it, using an epitope-tagged ACTR1B and determine the structure at a resolution sufficient to place the tag, or crosslink and map ACTR1B-ACTR1A and ACTR1B-CAPZ/ACTR10 crosslinks. The barbed and pointed ends are chemically distinct environments, so a preferred position would be functionally meaningful.
Experiment: Test whether the five conservative substitutions at the Arp1-Arp1 interface matter. The interface is 37/37 invariant between human and pig alpha-centractin at 90.3 per cent overall identity, yet ACTR1B differs at 5/37 at 90.4 per cent, which suggests relaxed constraint on a protomer that never has to tile the whole filament. Measure the critical concentration and elongation rate of homomeric beta-centractin filaments against alpha, and of an ACTR1A carrying the five beta residues (V45M, Y197L, S207T, I213V, I268V), to see whether beta is an intrinsically poorer polymer.
Experiment: A clean ACTR1B loss-of-function test. ACTR1B is a hit in only about 17 per cent of CRISPR screens against 48 per cent for ACTR1A, so knock out ACTR1B alone in cells where dynactin function can be read out quantitatively (single-molecule motility of purified dynactin, Golgi ribbon integrity, lysosome positioning) and ask whether anything changes. A genuinely null result would be worth recording, since it would mean the annotations on ACTR1B rest entirely on complex membership.
Experiment: Is the spectrin bridge paralog-specific? Golgi betaIII spectrin binds Arp1 directly, but that work used alpha-centractin reagents. Test recombinant ACTR1B against the two mapped Arp1-binding sites of betaIII spectrin alongside ACTR1A. This is the single experiment that would decide whether any membrane-anchor molecular function belongs on ACTR1B at all, rather than being inherited from its paralog.
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