RHOH GTPase cycle

Stable Identifier
R-HSA-9013407
Type
Pathway
Species
Homo sapiens
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RHOH is constitutively bound to GTP and does not require a guanine nucleotide exchange factor (GEF) for activation (Li et al. 2002). RHOH does not possess a GTPase activity (Li et al. 2002), but has been reported to bind to a small number of GTPase activator proteins (GAPs) (Bagci et al. 2020), which possibly function as RHOH effectors. While RHOH is not found in the GDP bound state, GDP dissociation inhibitors (GDIs), still interact with RHOH, presumably affecting its translocation to the site of activity by sequestering it in the cytosol (Li et al. 2002). Similar to RAC2, RHOH expression is also restricted to hematopoietic cells. RHOH function is required for T cell development and RHOH activity is regulated by posttranslational modifications downstream of activated T cell receptor (TCR). Following TCR activation, RhoH is degraded in lysosomes (Schmidt-Mende et al. 2010). In blood neutrophils from patients suffering from cystic fibrosis or eosinophils from patients with hypereosinophilic syndromes, an upregulation of RhoH expression has been found (Daryadel et al., 2009; Stoeckle et al., 2016). RHOH is subject to mutations and translocations in lymphoma (Suzuki and Oda 2008; Troeger and Williams 2013). Mutations in RHOH are associated with abnormal susceptibility to human beta-papillomavirus (beta-HPV) skin infections, which leads to epidermodysplasia verruciformis, a condition characterized by persistent flat warts or beta-HPV associated skin lesions (Przybyszewska et al. 2017).

Literature References
PubMed ID Title Journal Year
23850828 Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders

Troeger, A, Williams, DA

Exp. Cell Res. 2013
27740624 RhoH is a negative regulator of eosinophilopoiesis

Stoeckle, C, Geering, B, Yousefi, S, Rožman, S, Andina, N, Benarafa, C, Simon, HU

Cell Death Differ 2016
28196644 Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate

Przybyszewska, J, Zlotogorski, A, Ramot, Y

J. Am. Acad. Dermatol. 2017
19950172 Lysosomal degradation of RhoH protein upon antigen receptor activation in T but not B cells

Schmidt-Mende, J, Geering, B, Yousefi, S, Simon, HU

Eur J Immunol 2010
11809807 The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function

Li, X, Bu, X, Lu, B, Avraham, H, Flavell, RA, Lim, B

Mol. Cell. Biol. 2002
18311041 The atypical small GTPase RhoH : a novel role in T cell development

Suzuki, H, Oda, H

Nihon Rinsho Meneki Gakkai Kaishi 2008
31871319 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms

Bagci, H, Sriskandarajah, N, Robert, A, Boulais, J, Elkholi, IE, Tran, V, Lin, ZY, Thibault, MP, Dubé, N, Faubert, D, Hipfner, DR, Gingras, AC, Cote, JF

Nat. Cell Biol. 2020
19414807 RhoH/TTF negatively regulates leukotriene production in neutrophils

Daryadel, A, Yousefi, S, Troi, D, Schmid, I, Schmidt-Mende, J, Mordasini, C, Dahinden, CA, Ziemiecki, A, Simon, HU

J Immunol 2009
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