Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Electronic Gene Ontology annotations created by ARBA machine learning models
A vertebrate actin-related protein is a component of a multisubunit complex involved in microtubule-based vesicle motility.
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Identified centractin (actin-RPV) as a major component of dynactin, an activator of dynein-driven vesicle movement, and framed it as acting through a microtubule-based rather than myosin-based system.
"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."
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods.
Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation.
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GFP-Arp1A accumulates at the mitotic cell cortex, asymmetrically and distal to the spindle pole, downstream of LGN.
"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"
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LGN is required for cortical dynein-dynactin localisation, so in human cells dynactin is the anchored partner and Galphai-LGN-NuMA supplies the cortical anchor.
"we found that LGN was required for the cortical localization of dynein-dynactin"
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Regulation of spindle integrity and mitotic fidelity by BCCIP.
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GST-BCCIPalpha, but not BCCIPbeta or GST, pulled down the dynactin components p150Glued and Arp-1 from mitotic lysate - an isoform-specific interaction with the assembled complex.
"BCCIPα, but not BCCIPβ or GST itself, was sufficient to pull down the dynactin components, p150 glued and Arp-1"
Beta-centractin: characterization and distribution of a new member of the centractin family of actin-related proteins.
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Alpha- and beta-centractin are both dynactin subunits but occur in the complex at a constant ratio of about 15:1 in favour of alpha, despite comparable mRNA distribution - the basis for treating ACTR1A rather than ACTR1B as the filament subunit.
"The isoforms were found in a constant ratio of approximately 15:1 (alpha:beta) in the dynactin complex."
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Both isoforms are predominantly cytosolic and found as part of the 20S dynactin complex, with no free pool of either.
"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."
The structure of the dynactin complex and its interaction with dynein.
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Dynactin is built around an Arp1 filament of eight Arp1 subunits plus one beta-actin, capped by CapZ alpha-beta at the barbed end and Arp11 at the pointed end, giving a complex of exactly defined length.
"Together with CapZαβ binding to the barbed end this results in a highly stable complex of an exactly defined length."
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The dynein heavy-chain tails bind directly to the Arp1 filament, in clefts between adjacent protomers equivalent to the myosin site on actin, and the filament length forces dynein into its active conformation.
"They bind adjacent clefts between Arp1-D & F (chain-1) and Arp1-F & β-actin-H (chain-2) (Fig. 5F,G)."
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Arp1 and beta-actin share 53% sequence identity and both fold into four subdomains surrounding a nucleotide binding site.
"Both consist of four subdomains surrounding a nucleotide binding site (fig. S4)."
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Arp11 alone caps the pointed end; the other pointed-end subunits have a cargo-attachment role instead.
"Only Arp11 directly caps the pointed end, suggesting that the other components have a different role such as cargo attachment (28)."
The Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection.
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First cryo-EM structure of human dynactin (PDB 9B7J, 9B85), purified from human cell culture using the Chlamydia effector Dre1 as an affinity reagent; eight ACTR1A protomers are modelled, each with ADP.
"we purified dynactin from human cell culture and solved the first cryo-EM structure of human dynactin"
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Dre1 binds the pointed-end complex, not the Arp1 filament, so this paper is cited here for the human structure rather than for an ACTR1A interaction.
"these results suggest that Dre1 binds to the pointed-end complex of dynactin"
Self-regulated polymerization of the actin-related protein Arp1.
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Purified native Arp1 polymerises rapidly into short filaments of roughly dynactin length that anneal but never reach conventional actin-filament lengths.
"Arp1 was found to polymerize rapidly into short filaments that were similar, but not identical, in length to those in dynactin."
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Arp1's ATP binding is a prediction from conserved sequence features, not a measurement - which is why the nucleotide annotation proposed here is ADP binding, the ligand actually observed.
"on the basis of conserved sequence features, is predicted to bind ATP and possibly polymerize"
Ultrastructural analysis of the dynactin complex: an actin-related protein is a component of a filament that resembles F-actin.
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Anti-Arp1 antibodies decorate sites all along dynactin's 37 nm filament, showing that Arp1 itself assembles into a polymer similar to conventional actin, with capping protein at one end.
"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."
Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end.
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Arp11 was identified at the Arp1 mini-filament pointed end; like other Arps it retains the actin fold with its nucleotide and metal-binding elements, so fold retention alone does not discriminate a polymerising Arp from a capping one.
"Alignment of the Arp11 sequence with actin reveals overall conservation of the “actin fold,” a primordial core structure that contains nucleotide and metal binding elements"
Structure of dynein-dynactin on microtubules shows tandem adaptor binding.
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Cargo-adaptor coiled coils run along dynactin's filament and position dynein in a conformation that relieves its intrinsic inhibition.
"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"
Cryo-EM reveals the complex architecture of dynactin's shoulder region and pointed end.
Dynactin's pointed-end complex is a cargo-targeting module.
Dynactin and Num1 cooperate to establish the cortical anchoring of cytoplasmic dynein in S. pombe.
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Fission-yeast Arp1, Mug5 and Jnm1 colocalise with cortical dynein foci and are required for cortical dynein anchoring, in cooperation with the cortical factor Num1/Mcp5.
"These subunits transiently colocalized with dynein foci at the cell cortex and were essential for the cortical anchoring of dynein."
Isolation of a new set of Aspergillus nidulans mutants defective in nuclear migration.
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nudK encodes the actin-related protein Arp1, giving the first evidence that dynactin is involved in nuclear migration in A. nidulans.
"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."
The yeast dynactin complex is involved in partitioning the mitotic spindle between mother and daughter cells during anaphase B.
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Budding-yeast Act5p/Arp1 exists in a stable dynactin complex with Nip100p (p150Glued homolog) and Jnm1p; this is also the source of yeast ARP1's own IDA for GO:0005200.
"Consistent with the presence of a true dynactin complex in yeast, Nip100p exists in a stable complex with Act5p as well as Jnm1p, another protein required for proper spindle partitioning during anaphase."
Cross-linking Proteomics Indicates Effects of Simvastatin on the TLR2 Interactome and Reveals ACTR1A as a Novel Regulator of the TLR2 Signal Cascade.
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ACTR1A was found in the cross-linked TLR2 interactome and its knockdown reduced pro-inflammatory cytokine induction.
"RNA interference studies revealed an important role for ACTR1A in induction of pro-inflammatory cytokines."
Alpha-centractin is a novel substrate of SETD3 methyltransferase in vitro.
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Recombinant SETD3 methylates ACTR1A in vitro, extending its substrate repertoire beyond beta-actin; no in-cell methylation site was mapped.
"In this study, we report the identification of α-centractin (ACTR1A) as a novel SETD3 substrate in vitro."
UniProtKB record for human ACTR1A
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UniProt describes ACTR1A as part of the ACTR1A/ACTB filament around which dynactin is built, containing 8 copies of ACTR1A and 1 ACTB, and places it in the actin family, ARP1 subfamily.
"The filament contains 8 copies of ACTR1A and 1 ACTB."
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The record still cross-references GO:0005200 (IBA:GO_Central) and GO:0005524 (IEA:UniProtKB-KW) and reports two PAN-GO annotations, none of which is present in current GOA for P61163.
"DR PAN-GO; P61163; 2 GO annotations based on evolutionary models."
Bioinformatics: ACTR1A nucleotide site and polymerisation interface
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ACTR1A retains 19 of 25 beta-actin nucleotide-contact residues (76%), ACTR1B 20/25, and the capping paralog ACTR10 only 10/25 (40%).
"| ACTR10 | 28.0 | 25 | 10 | 40.0 |"
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All eight ACTR1A protomers of the human dynactin structure (PDB 9B85) have ADP modelled, in the cleft homologous to actin's ATP site.
"ACTR1A chains with a modelled nucleotide: **8/8**, ligand(s) ADP."
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All six large (intra-protofilament) ACTR1A-ACTR1A interfaces share ACTR1A residues 44-49, 51, 52 and 65-68, which map onto beta-actin's subdomain-2 DNase-I-binding loop - actin's own longitudinal polymerisation contact - plus subdomain-3/4 contacts at beta-actin 200, 208 and 242-245.
"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]."
Affinage mechanistic annotation for ACTR1A (human)
Curator notes for human ACTR1A
Transport of antigen loaded MHC II molecules to surface
AJUBA facilitates AURKA autophosphorylation
AJUBA binds centrosome-associated AURKA
AURKA phosphorylates PLK1
BORA binds PLK1 and AURKA
Plk1-mediated phosphorylation of Nlp
Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome
Loss of C-Nap-1 from centrosomes
Dissociation of Phospho-Nlp from the centrosome
Recruitment of Plk1 to centrosomes
Association of NuMA with microtubules
Recruitment of CDK11p58 to the centrosomes
Translocation of NuMA to the centrosomes
RAB3IP stimulates nucleotide exchange on RAB8A
C2CD3 binds the mother centriole
C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole
CP110 and CEP97 dissociate from the centriole
The distal appendage proteins recruit TTBK2
Recruitment of transition zone proteins
MARK4 binds ODF2 in the centriole
CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
ERGIC-to-Golgi vesicles bind dynein:dynactin
Vesicle is tethered through binding GOLGA2:GORASP1, GOLGB1 and the COG complex
RAB6:GTP displaces PAFAH1B1 from dynein:dynactin complex
Dynein drives COPI-independent retrograde traffic from the Golgi to the ER
TPX2 binds AURKA at centrosomes
TPX2 promotes AURKA autophosphorylation