Actin-related protein 2/3 complex subunit 3 (ARPC3)
The protein contains 178 amino acids for an estimated molecular weight of 20547 Da.
Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). 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: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). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
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
Cellular response to nerve growth factor stimulus
Ephrin receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
Membrane organization
The reference OMIM entry for this protein is 604225
Actin-related protein 2/3 complex, subunit 3; arpc3
Actin-related protein 2/3 complex, 21-kd subunit; arc21
P21-arc
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; 604222), ARC41 (ARPC1B; 604223), ARC34 (ARPC2; 604224), ARC21 (ARPC3), 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 ARC21 cDNA encodes a deduced 178-amino acid protein that is 45% identical to its homolog in S. cerevisiae. ARC21 localizes to the lamellipodia of stationary and motile fibroblasts, as well as to the actin tails assembled by Listeria monocytogenes. ARC21 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. They identified full-length human cDNAs encoding ARC34, ARC21, and ARC16. ARC34 and ARC21 were localized in the cytoplasm of fibroblasts lacking lamellipodia, but became enriched in the lamellipodia of stimulated fibroblasts.GENE FUNCTION
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.BIOCHEMICAL FEATURES
- Crystal Structure 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
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 604225 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).