RHOBTB GTPase Cycle (Homo sapiens)

Quality Tags

Ontology Terms

Saving...

Bibliography

1. Sreeramulu S, Jonker HR, Langer T, Richter C, Lancaster CR, Schwalbe H.; ''The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy.''; PubMed Europe PMC Scholia
2. Lu A, Pfeffer SR.; ''Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation and promotes cell cycle progression.''; PubMed Europe PMC Scholia
3. Pridgeon JW, Webber EA, Sha D, Li L, Chin LS.; ''Proteomic analysis reveals Hrs ubiquitin-interacting motif-mediated ubiquitin signaling in multiple cellular processes.''; PubMed Europe PMC Scholia
4. Matthys A, Van Craenenbroeck K, Lintermans B, Haegeman G, Vanhoenacker P.; ''RhoBTB3 interacts with the 5-HT7a receptor and inhibits its proteasomal degradation.''; PubMed Europe PMC Scholia
5. Espinosa EJ, Calero M, Sridevi K, Pfeffer SR.; ''RhoBTB3: a Rho GTPase-family ATPase required for endosome to Golgi transport.''; PubMed Europe PMC Scholia
6. Schenková K, Lutz J, Kopp M, Ramos S, Rivero F.; ''MUF1/leucine-rich repeat containing 41 (LRRC41), a substrate of RhoBTB-dependent cullin 3 ubiquitin ligase complexes, is a predominantly nuclear dimeric protein.''; PubMed Europe PMC Scholia
7. Zhang CS, Liu Q, Li M, Lin SY, Peng Y, Wu D, Li TY, Fu Q, Jia W, Wang X, Ma T, Zong Y, Cui J, Pu C, Lian G, Guo H, Ye Z, Lin SC.; ''RHOBTB3 promotes proteasomal degradation of HIFα through facilitating hydroxylation and suppresses the Warburg effect.''; PubMed Europe PMC Scholia
8. Choi YM, Kim KB, Lee JH, Chun YK, An IS, An S, Bae S.; ''DBC2/RhoBTB2 functions as a tumor suppressor protein via Musashi-2 ubiquitination in breast cancer.''; PubMed Europe PMC Scholia
9. Berthold J, Schenková K, Ramos S, Miura Y, Furukawa M, Aspenström P, Rivero F.; ''Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes--evidence for an autoregulatory mechanism.''; PubMed Europe PMC Scholia
10. Haga RB, Garg R, Collu F, Borda D'Agua B, Menéndez ST, Colomba A, Fraternali F, Ridley AJ.; ''RhoBTB1 interacts with ROCKs and inhibits invasion.''; PubMed Europe PMC Scholia
11. Manjarrez JR, Sun L, Prince T, Matts RL.; ''Hsp90-dependent assembly of the DBC2/RhoBTB2-Cullin3 E3-ligase complex.''; PubMed Europe PMC Scholia
12. Berthold J, Schenkova K, Rivero F.; ''Rho GTPases of the RhoBTB subfamily and tumorigenesis.''; PubMed Europe PMC Scholia
13. Ji W, Rivero F.; ''Atypical Rho GTPases of the RhoBTB Subfamily: Roles in Vesicle Trafficking and Tumorigenesis.''; PubMed Europe PMC Scholia
14. Vaughan CK, Gohlke U, Sobott F, Good VM, Ali MM, Prodromou C, Robinson CV, Saibil HR, Pearl LH.; ''Structure of an Hsp90-Cdc37-Cdk4 complex.''; PubMed Europe PMC Scholia
15. Mukohda M, Fang S, Wu J, Agbor LN, Nair AR, Ibeawuchi SC, Hu C, Liu X, Lu KT, Guo DF, Davis DR, Keen HL, Quelle FW, Sigmund CD.; ''RhoBTB1 protects against hypertension and arterial stiffness by restraining phosphodiesterase 5 activity.''; PubMed Europe PMC Scholia
16. Wilkins A, Ping Q, Carpenter CL.; ''RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:456216 (ChEBI)
ATP	Metabolite	CHEBI:30616 (ChEBI)
ATP	Metabolite	CHEBI:30616 (ChEBI)
CCNE1	Protein	P24864 (Uniprot-TrEMBL)
CDC37	Protein	Q16543 (Uniprot-TrEMBL)
CUL3	Protein	Q13618 (Uniprot-TrEMBL)
GTP	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HGS	Protein	O14964 (Uniprot-TrEMBL)
HSP90:CDC37	Complex	R-HSA-9693661 (Reactome)
HSP90AA1	Protein	P07900 (Uniprot-TrEMBL)
HSP90AB1	Protein	P08238 (Uniprot-TrEMBL)
HTR7	Protein	P34969-2 (Uniprot-TrEMBL)
LRRC41	Protein	Q15345 (Uniprot-TrEMBL)
PLIN3	Protein	O60664 (Uniprot-TrEMBL)
Pi	Metabolite	CHEBI:43474 (ChEBI)
RAB9A	Protein	P51151 (Uniprot-TrEMBL)
RAB9B	Protein	Q9NP90 (Uniprot-TrEMBL)
RHOBTB1	Protein	O94844 (Uniprot-TrEMBL)
RHOBTB1 interacting proteins	Complex	R-HSA-9020314 (Reactome)
RHOBTB1:GTP:RHOBTB1 interacting proteins	Complex	R-HSA-9020317 (Reactome)
RHOBTB1:GTP	Complex	R-HSA-9020318 (Reactome)
RHOBTB1	Protein	O94844 (Uniprot-TrEMBL)
RHOBTB2	Protein	Q9BYZ6 (Uniprot-TrEMBL)
RHOBTB2 interacting proteins	Complex	R-HSA-9020341 (Reactome)
RHOBTB2:GTP:RHOBTB2 interacting proteins	Complex	R-HSA-9020346 (Reactome)
RHOBTB2:GTP	Complex	R-HSA-9020344 (Reactome)
RHOBTB2	Protein	Q9BYZ6 (Uniprot-TrEMBL)
RHOBTB3	Protein	O94955 (Uniprot-TrEMBL)
RHOBTB3 interacting proteins	Complex	R-HSA-9706395 (Reactome)
RHOBTB3:ADP	Complex	R-HSA-6814647 (Reactome)
RHOBTB3:ATP:RHOBTB3 interacting proteins	Complex	R-HSA-9706391 (Reactome)
RHOBTB3:ATP	Complex	R-HSA-6814649 (Reactome)
RHOBTB3	Protein	O94955 (Uniprot-TrEMBL)
ROCK1	Protein	Q13464 (Uniprot-TrEMBL)
ROCK2	Protein	O75116 (Uniprot-TrEMBL)
VHL	Protein	P40337 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
ATP			R-HSA-9706393 (Reactome)
GTP			R-HSA-9018774 (Reactome)
GTP			R-HSA-9018785 (Reactome)
H2O			R-HSA-9706399 (Reactome)
HSP90:CDC37		mim-catalysis	R-HSA-9018785 (Reactome)
	Pi	Arrow	R-HSA-9706399 (Reactome)
			R-HSA-9018774 (Reactome)	RHOBTB1 shares 80% sequence identity with RHOBTB2, with close to 95% identity in the GTPase domain (reviewed by Ji and Rivero 2016). Based on studies in RHOBTB2 (Manjarrez et al. 2014), as well as on the primary structure of the GTPase domain, RHOBTB1 is expected to bind to GTP, but not to cycle between GTP- and GDP-bound states. There are no known RHOBTB1 GAPs.
			R-HSA-9018778 (Reactome)	RHOBTB1, like other members of RHOBTB family, RHOBTB2 and RHOBTB3, binds to CUL3 (cullin-3), a core component of the BTB-CUL3-RBX2 E3 ubiquitin ligase complex (Berthold et al. 2008). RHOBTB1 binds to ROCK1 and ROCK2, and ROCK-mediated phosphorylation of RHOBTB1 may regulate its association with CUL3 (Haga et al. 2019). RHOBTB1 has been proposed as a substrate adaptor for PDE5, targeting it to CUL3 complexes for ubiquitination (Mukohda et al. 2019).
			R-HSA-9018785 (Reactome)	RHOBTB2 binds to GTP, but does not switch between GDP- and GTP-bound states (Manjarrez et al. 2014). ATP-dependent protein folding chaperone activity of the HSP90:CDC37 complex and binding of RHOBTB2 to the HSP90:CDC37 complex enables RHOBTB2 to bind GTP (Manjarrez et al. 2014). There are no known RHOBTB2 GAPs.
			R-HSA-9018787 (Reactome)	RHOBTB2, like other RHOBTB family members, RHOBTB1 and RHOBTB3, binds CUL3 (cullin-3) (Berthold et al. 2008), a core component of BTB-CUL3-RBX1 E3 ubiquitin ligase complexes. Binding of GTP to RHOBTB2, facilitated by the HSP90 chaperone complex, enables binding of RHOBTB2 to CUL3 (Manjarrez et al. 2014). RHOBTB2 is thought to act as the regulatory BTB component of the BTB-CUL3-RBX1 complex by recruiting target proteins for ubiquitination and subsequent proteasome-mediated degradation (Wilkins et al. 2004). RHOBTB2 is a substrate adaptor for Musashi 2 (MSI2), targeting it to CUL3 complexes for ubiquitination and proteasomal degradation, thus suppressing tumorigenesis (Choi et al. 2017).
			R-HSA-9706390 (Reactome)	RHOBTB3, like other RHOBTB family members, RHOBTB1 and RHOBTB2, binds CUL3 (cullin 3) a core component of BTB:CUL3:RBX1 E3 ubiquitin ligase complexes (Berthold et al. 2008). The following proteins are substrates of RHOBTB3-dependent ubiquitin ligase complexes: RAB9A, RAB9B (Espinosa et al. 2009) Cyclin E1 (Lu and Pfeffer 2013) LRRC41 (MUF1) (Schenková et al. 2012). The following proteins bind directly to RHOBTB3 but there is no evidence that they are substrates of RHOBTB3-dependent ubiquitin ligase complexes: HGS (HRS) (Pridgeon et al. 2009) PLIN3 (TIP47) (Espinosa et al. 2009) 5-HT7a serotonin receptor (Matthys et al. 2012) VHL (Zhang et al. 2015).
			R-HSA-9706393 (Reactome)	The GTPase domain of RHOBTB3 is considerably divergent and binds ATP instead of GTP by virtue of some critical amino acid replacements in the G4 and G5 motifs (Espinosa et al. 2009).
			R-HSA-9706399 (Reactome)	The GTPase domain of RHOBTB3 is considerably divergent and binds and hydrolyzes ATP instead of GTP by virtue of some critical amino acid replacements in the G4 and G5 motifs (Espinosa et al. 2009). Binding of Rab9 increases the ATPase activity (Espinosa et al. 2009).
RHOBTB1 interacting proteins			R-HSA-9018778 (Reactome)
	RHOBTB1:GTP:RHOBTB1 interacting proteins	Arrow	R-HSA-9018778 (Reactome)
	RHOBTB1:GTP	Arrow	R-HSA-9018774 (Reactome)
RHOBTB1:GTP			R-HSA-9018778 (Reactome)
RHOBTB1			R-HSA-9018774 (Reactome)
RHOBTB2 interacting proteins			R-HSA-9018787 (Reactome)
	RHOBTB2:GTP:RHOBTB2 interacting proteins	Arrow	R-HSA-9018787 (Reactome)
	RHOBTB2:GTP	Arrow	R-HSA-9018785 (Reactome)
RHOBTB2:GTP			R-HSA-9018787 (Reactome)
RHOBTB2			R-HSA-9018785 (Reactome)
RHOBTB3 interacting proteins			R-HSA-9706390 (Reactome)
	RHOBTB3:ADP	Arrow	R-HSA-9706399 (Reactome)
	RHOBTB3:ATP:RHOBTB3 interacting proteins	Arrow	R-HSA-9706390 (Reactome)
	RHOBTB3:ATP	Arrow	R-HSA-9706393 (Reactome)
RHOBTB3:ATP			R-HSA-9706390 (Reactome)
RHOBTB3:ATP			R-HSA-9706399 (Reactome)
RHOBTB3:ATP		mim-catalysis	R-HSA-9706399 (Reactome)
RHOBTB3			R-HSA-9706393 (Reactome)