Actin-related protein 2/3 complex subunit 2 (ARPC2)

The protein contains 300 amino acids for an estimated molecular weight of 34333 Da.

 

Actin-binding 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). Seems to contact the mother actin filament (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: Nov. 7, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 604224

Actin-related protein 2/3 complex, subunit 2; arpc2
Actin-related protein 2/3 complex, 34-kd subunit; arc34
P34-arc

DESCRIPTION

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), ARC21 (ARPC3; 604225), ARC20 (ARPC4; 604226), and ARC16 (ARPC5; 604227) (summary by Welch et al., 1997). 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 ARC34 cDNA encodes a deduced 300-amino acid protein that is 34% identical to its homolog in S. cerevisiae. ARC34 localizes to the lamellipodia of stationary and motile fibroblasts, as well as to the actin tails assembled by Listeria monocytogenes. ARC34 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. Western blot analysis detected ARP3 and ARC34 in all human tissues tested. 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.

MAPPING

Welch et al. (1997) noted that a partial sequence of ARC34 (GenBank GENBANK U50523) was mapped to the BRCA2 (600185) region on chromosome 13q12-q13 by Couch et al. (1996). However, Gross (2011) mapped the ARPC2 gene to chromosome 2q35 based on an alignment of the ARPC2 sequence (GenBank GENBANK BC000590) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 604224 was added.