Reactome | RHOH GTPase cycle

RHOH GTPase cycle

Stable Identifier

R-HSA-9013407

DOI

10.3180/R-HSA-9013407.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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
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
23850828	Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders Troeger, A, Williams, DA	Exp. Cell Res.	2013
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