Ras-related C3 botulinum toxin substrate 2 (RAC2)

The protein contains 192 amino acids for an estimated molecular weight of 21429 Da.

 

Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. 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.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 0
No model available.

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VariantDescription
a breast cancer sample; somatic mutation
IMD73A

The reference OMIM entry for this protein is 602049

Ras-related c3 botulinum toxin substrate 2; rac2
Rho family, small gtp-binding protein rac2

CLONING

Members of the RAS superfamily of small GTP-binding proteins (see 190020) appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Didsbury et al. (1989) identified 2 human cDNAs, called RAC1 (602048) and RAC2 by them, that are 92% identical and share 58% and 26 to 30% amino acid identity with human RHOS and RAS, respectively. The 2 genes encode the C-terminal consensus sequence (CXXX-COOH), which localizes RAS to the inner plasma membrane, and the residues gly12 and ala59, at which sites mutations elicit transforming potential to RAS. RAC2 mRNA displayed relative myeloid tissue selectivity and showed an increase upon differentiation of HL-60 and U937 cells to neutrophil-like and monocyte-like morphology, respectively. Using transfection experiments, Didsbury et al. (1989) showed that RAC1 and RAC2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. See also RAC3 (602050).

GENE FUNCTION

Using a cDNA subtraction method, representational display analysis, Li et al. (2000) showed that Rac2 is selectively expressed in mouse type 1 helper T lymphocytes (Th1). Rac2 induces the interferon-gamma (147570) promoter through cooperative interaction of the NF-kappa-B (164011) and p38 MAP kinase (600289) pathways. Diebold and Bokoch (2001) showed that RAC2 is required for the transfer of electrons from NADPH to cytochrome b-associated FAD, then to cytochrome b heme, and finally to oxygen. Using site-specific mutants, they showed that RAC2 acts independently of p67-phox (233710) to regulate the initial transfer of electrons from NADPH to FAD and that RAC2 binding to p67-phox is necessary to complete electron transfer to molecular oxygen to form superoxide anion. Gu et al. (2002) found that the expression of 38 known genes was significantly altered in Rac2 -/- mouse mast cells after cytokine stimulation compared with those of wildtype cells. Of these, Mcp7 (TPSAB1; 191080) transcription in wildtype cells was increased 4-fold after stimulation with stem cell factor (SCF) (KITLG; 184745); however, in spite of a compensatory Rac1 increase in Rac2-deficient cells, SCF-induced Mcp7 transcription did not occur in these cells. Gu et al. (2002) concluded that in Rac2 -/- mast cells loss of Mcp7 induction was due to reduced Jnk (see MAPK8; 601158) activity but not due to reduced NFKB (see 164011) activity. By studying host responses to E. coli cytotoxic necrotizing factor-1 (CNF1) in Drosophila and human cells, Boyer et al. (2011) showed that the host indirectly sensed the pathogen via its modification and activation of RAC2. After CNF1 modified RAC2, RAC2 interacted with the innate immune adaptors Imd and RIPK1 (603453)-RIPK2 (603455) in flies and human cells, respectively. Induction of the immune response in flies required CNF1 enzymatic activity, which, in mammals, catalyzes deamidation of a glutamine to glutamic acid in RAC2, abolishing GTPase activity and locking the enzyme into an active form. Modified RAC2 interacted with RIPK1 and RIPK2 to induce immune activation via NFKB and IL8 (146930) expression in human cells. Boyer et al. (2011) concluded that virulence factors such as CNF1 induce an immune response through this mechanism, whereas avirulent microbes fail to provoke host responses.

GENE STRUCTURE

Courjal et al. (1997) determined that RAC2 is made up of at least 7 exons, spanning ov ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 602049 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).