ARHGAP21 (Rho GTPase activating protein 21)

	Figure 1. Schematic representation of ARHGAP21 protein. Domain positions were based on National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm.nih.gov/gene/57584).
Description	RhoGAPs are usually large proteins with additional domains other than the RhoGAP domain (Tcherkezian and Lamarche-Vane 2007). ARHGAP21 is composed of 1958 amino acids and has a predicted molecular weight of 217 kDa. In addition to the RhoGAP domain, ARHGAP21 comprises a PH (pleckstrin homology) and a PDZ domain (Figure 1). Although PH domains can bind to phosphatidylinositol lipids within biological membranes (Harlan et al. 1994; Saito et al. 2001), the ARHGAP21 PH domain has been demonstrated to not bind to lipids (Dubois et al. 2005). ARHGAP21 has been described to be SUMOylated in lysine K1443 by SUMO2/3. This post-translational modification may possibly explain the higher weight found by mass spectrometry (250 kDa) in contrast with the predicted weight (Bigarella et al. 2009).
Expression	ARHGAP21 gene was widely expressed in a panel of different human tissues. Higher ARHGAP21 gene expression was observed in brain, heart, skeletal muscle, and placenta (Basseres et al. 2002). Results from FANTOM5 project also showed an increased ARHGAP21 gene expression in tissues of the human nervous system, such as cerebellum, diencephalon and hippocampus (Expression Atlas data bank).
Localisation	ARHGAP21 has been shown to localize in the nuclei and cytoplasm of different cell types, such as adenocarcinoma PC3 and LNCAP cells and in glioblastoma T98G cells (Bigarella et al. 2009; Lazarini et al. 2013). In epithelial Caco-2 and JEG-3 cells, ARHGAP21 was detected at the cell-cell junctions and at the nucleus and perinuclear region (Sousa et al. 2005). Breast adenocarcinoma MCF-7 cells and HeLa cells presented ARHGAP21 localization in Golgi complex and in vesicular cytoplasmic structures (Dubois et al. 2005). In cardiomyocytes, ARHGAP21 was relocated from the nucleus to Z-lines and costameres after pressure overload (Borges et al. 2008).
Function	ARHGAP21 acts as a RhoGAP for RHOA, RHOC andCDC42, but not for RAC1 (Dubois et al. 2005; Sousa et al. 2005; Lazarini et al. 2013). Such as occurs with other RhoGAP proteins, the ARHGAP21 RhoGAP activity has not been tested for most Rho GTPases. However, several ARHGAP21 partners have been described, suggesting that ARHGAP21 functions as a scaffold, linking Rho GTPases to other signaling pathways. ARHGAP21 has been shown to interact with ARF1, ARF6 (Dubois et al. 2005), catenin alpha (Sousa et al. 2005), PTK2 (FAK), PRKCZ (PKC zeta) (Borges et al. 2008), arrestin beta (Anthony et al. 2011), tubulin alpha (Barcellos et al. 2013), PRICKLE1 (Zhang et al. 2016). The functions of ARHGAP21 have been investigated in several types of cells. ARHGAP21 plays a role in cell proliferation (Lazarini et al. 2013; Luo et al. 2016), migration (Bigarella et al. 2009; Lazarini et al. 2013), vesicle traffic (Dubois et al. 2005), cell adhesions (Sousa et al. 2005; Barcellos et al. 2013; Zhang et al. 2016) and insulin secretion (Ferreira et al. 2015).
Homology	ARHGAP21 shares homology with other members of the RhoGAP protein family (Tcherkezian and Lamarche-Vane 2007). ARHGAP21 also presents high homology among different species (Table 1). Table 1. Comparative identity of human ARHGAP21 with other species % Identity for: Homo sapiens ARHGAP21 Symbol Protein DNA vs. P. troglodytes ARHGAP21 99.5 99.5 vs. M. mulatta ARHGAP21 98.2 98.0 vs. C. lupus ARHGAP21 87.1 85.6 vs. B. taurus ARHGAP21 87.3 85.0 vs. M. musculus Arhgap21 87.3 84.0 vs. R. norvegicus Arhgap21 86.9 83.3 vs. G. gallus ARHGAP21 74.9 75.1 vs. X. tropicalis arhgap21 65.1 67.4 vs. D. rerio arhgap21 57.9 59.5 (Source: http://www.ncbi.nlm.nih.gov/homologene)

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