Actin-related protein 3 (ACTR3)
The protein contains 418 amino acids for an estimated molecular weight of 47371 Da.
ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation (PubMed:29058690). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:17220302, PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). Plays a role in ciliogenesis (PubMed:20393563). (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Actin polymerization-dependent cell motility
Arp2/3 complex-mediated actin nucleation
Asymmetric cell division
Cellular response to interferon-gamma
Cilium assembly
Ephrin receptor signaling pathway
Establishment or maintenance of cell polarity
Fc-gamma receptor signaling pathway involved in phagocytosis
Meiotic chromosome movement towards spindle pole
Meiotic cytokinesis
Membrane organization
Positive regulation of lamellipodium assembly
Positive regulation of transcription by RNA polymerase II
Spindle localization
The reference OMIM entry for this protein is 604222
Actin-related protein 3; actr3
Arp3
The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells. The human complex consists of 7 subunits: the actin-related proteins ARP2 (ACTR2; 604221) and ARP3 (ACTR3), ARC41 (ARPC1B; 604223), ARC34 (ARPC2; 604224), ARC21 (ARPC3; 604225), ARC20 (ARPC4; 604226), and ARC16 (ARPC5; 604227). See ACTR2 for additional information about the Arp2/3 complex.
CLONING
By searching an EST database with peptide sequences from the 7 subunits of the human ARP2/3 complex, Welch et al. (1997) identified full-length human cDNAs encoding each subunit. The ARP3 cDNA encodes a deduced 418-amino acid protein that is identical to bovine Arp3, 59% identical to S. pombe Arp3, and 58% identical to S. cerevisiae Arp3. ARP3 localizes to the lamellipodia of stationary and locomoting fibroblasts. It also localizes to the actin tails assembled by moving intracellular Listeria monocytogenes bacteria and to actin clouds surrounding stationary L. monocytogenes (Welch et al., 1997). ARP3 was not detected in cellular bundles of actin filaments. Machesky et al. (1997) purified the ARP2/3 complex from human neutrophils and sequenced peptides from each of the subunits. Western blot analysis detected ARP3 and ARC34 in all human tissues tested.GENE FUNCTION
In a functional genomic screen using RNA interference to identify human genes involved in ciliogenesis control, Kim et al. (2010) identified 2 gelsolin family proteins, GSN (137350) and AVIL (613397), which regulate cytoskeletal actin organization by severing actin filaments. Depletion of GSN proteins by 2 independent siRNAs significantly reduced ciliated cell numbers, indicating that actin filament severing is involved in ciliogenesis. In contrast, silencing of actin-related protein ACTR3, which is a major constituent of the ARP2/3 complex that is necessary for nucleating actin polymerization at filament branches, caused a significant increase in cilium length and also facilitated ciliogenesis independently of serum starvation. Kim et al. (2010) concluded that their observations indicated an inhibitory role of branched actin network formation in ciliogenesis.BIOCHEMICAL FEATURES
Volkmann et al. (2001) performed electron cryomicroscopy and 3-dimensional reconstruction of Acanthamoeba castellanii and S. cerevisiae Arp2/3 complexes bound to the WASP (301000) carboxy-terminal domain. Asymmetric, oblate ellipsoids were revealed. Image analysis of actin branches indicated that the complex binds the side of the mother filament, and ARP2 and ARP3 are the first 2 subunits of the daughter filament. Comparison to the actin-free WASP-activated complexes suggests that branch initiation involves large-scale structural rearrangements within ARP2/3. Robinson et al. (2001) determined the crystal structure of bovine ARP2/3 complex at 2.0-angstrom resolution. ARP2 and ARP3 are folded like actin, with distinctive surface features. Subunits ARPC2 and ARPC4 in the core of the complex associate through long carboxy-terminal alpha helices and have similarly folded amino-terminal alpha/beta domains. ARPC1 is a 7-blade beta propeller with an insertion that may associate with the side of an actin filament. ARPC3 and ARPC5 are globular alpha-helical subunits. Robinson et al. (2001) predicted that WASP/SCAR proteins activate ARP2/3 complex by bringing ARP2 into proximity with ARP3 for nucleation of a branch on the side of a preexisting actin filament. ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 604222 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).