Actin-related protein 2 (ACTR2)

The protein contains 394 amino acids for an estimated molecular weight of 44761 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). (updated: April 22, 2020)

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.

Interpro domains
Total structural coverage: 100%
Model score: 24

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The reference OMIM entry for this protein is 604221

Actin-related protein 2; actr2
Arp2 arp2/3 complex, included

CLONING

The protrusion of the cell membrane is fundamental to cell shape change and locomotion. Actin polymerization (see 102560) plays a critical role in this process. The leading edge of motile cells is dominated by thin actin-rich structures called lamellipodia, which exhibit highly dynamic behavior characterized by rapid extension and retraction. Many aspects of the mechanism of lamellipodial protrusion are echoed in the intracellular motility of certain bacterial and viral pathogens, such as the bacterium Listeria monocytogenes. Welch et al. (1997) purified an approximately 220-kD multiprotein complex from human platelets that induces actin polymerization at the L. monocytogenes cell surface and mediates bacterial motility. This complex contains actin-related proteins (Arps) in the Arp2 and Arp3 families and therefore was named the Arp2/3 complex. In addition to 43-kD ARP2 and 50-kD ARP3 (ACTR3; 604222), the human complex consists of 41/40- (ARPC1B; 604223), 34- (ARPC2; 604224), 21- (ARPC3; 604225), 20- (ARPC4; 604226), and 16-kD (ARPC5; 604227) subunits, all present in approximately equal stoichiometry. 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 ARP2 cDNA encodes a deduced 394-amino acid protein that is 99% identical to chicken Arp2 and 67% identical to S. cerevisiae Arp2. Welch et al. (1997) localized several subunits of the ARP2/3 complex to the lamellipodia of stationary and locomoting fibroblasts, as well as to the actin tails assembled by L. monocytogenes. They suggested that the ARP2/3 complex promotes actin assembly in lamellipodia and may participate in lamellipodial protrusion. Machesky et al. (1997) purified the ARP2/3 complex from human neutrophils and sequenced peptides from each of the subunits.

GENE FUNCTION

Leisel et al. (1999) used pure components of the actin cytoskeleton to reconstitute sustained movement in Listeria and Shigella in vitro. Actin-based propulsion was driven by the free energy released by ATP hydrolysis linked to actin polymerization and did not require myosin (see 601478). In addition to actin and activated Arp2/3 complex, actin depolymerizing factor and capping protein (see 601571) were also required for motility as they maintained a high steady-state level of G-actin (see 102610), which controls the rate of unidirectional growth of actin filaments at the surface of the bacterium. The movement was more effective when profilin (see 176610), alpha-actinin (see 102575), and, in the case of Listeria, VASP (601703) were also included. The protein N-WASP (WASL; 605056) regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. N-WASP is tightly regulated by multiple signals; only costimulation by CDC42 (116952) and phosphatidylinositol (4,5)-bisphosphate (PIP2) yields potent polymerization. Prehoda et al. (2000) found that regulation requires N-WASP's constitutively active output domain (verprolin/cofilin/acidic (VCA) domain) and 2 regulatory domains, a CDC42-binding domain and a PIP2-binding domain. In the absence of stimuli, the regulatory modules together hold the VCA-Arp2/3 complex in an inactive 'closed' conformation. In this state, both the CDC42- and PIP2-binding sites are masked. Binding of either input destabilizes the closed state and enhances binding of the other input. This cooperative activa ... More on the omim web site

Subscribe to this protein entry history

April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 604221 was added.