RGGT geranylgeranylates RAB proteins

Stable Identifier
Reaction [transition]
Homo sapiens
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RAB geranylgeranyltransferase (GGTase) recognizes and geranylgeranylates cysteine residues in -CXCX, -CCXX or -XXCC motifs in the C-termini of RAB proteins. Most RAB proteins are doubly geranylgeranylated, most likely in a sequential fashion, but some are only singly modified (Baron and Seabra, 2008; Farnsworth et al 1994; Wilson et al, 1996; Overmeyer et al, 2000; Khosravi-Far et al, 1991; Joberty et al, 1993; Catherman et al, 2013; Leung et al, 2007; Maurer-Stroh et al, 2007). In most cases, geranylgeranylation is required for proper localization and function of the RAB proteins. After geranylgeranylation, RABs remain associated with the RAB escort protein CHM or CHML, which dissociates when the GTPase reaches its target membrane (Alexandrov et al, 1994; Seabra et al, 1996; Shen and Seabra, 1996). Release of the geranylgeranyl RAB:CHM complex from the catalytic subunits is promoted by the binding of additional GGPP to the enzyme (Baron and Seabra, 2008). Once prenylated, RABs cycle between active GTP bound forms that are membrane associated, and inactive GDP bound forms that are cytosolic and associated with RAB GDP dissociation inhibitor (GDI) proteins. Conversion between these states is governed by the activities of guanine nucleotide exchange factors (GEFs), which promote the exchange of GDP for GTP, and GTPase activating proteins (GAPs), which stimulate the intrinsic GTPase activity of RABs (Ullrich et al, 1993; Soldati et al, 1994; reviewed in Wandinger-Ness and Zerial, 2014; Stenmark, 2009).
Literature References
PubMed ID Title Journal Year
8662963 Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDP-bound Rab

Seabra, MC

J. Biol. Chem. 1996
19603039 Rab GTPases as coordinators of vesicle traffic

Stenmark, H

Nat. Rev. Mol. Cell Biol. 2009
8836150 Prenylation of a Rab1B mutant with altered GTPase activity is impaired in cell-free systems but not in intact mammalian cells

Sheridan, KM, Erdman, RA, Wilson, AL, Maltese, WA

Biochem. J. 1996
1648736 Isoprenoid modification of rab proteins terminating in CC or CXC motifs

Der, CJ, Balch, WE, Khosravi-Far, R, Buss, JE, Sinensky, M, Conroy, L, Bourne, JR, Lutz, RJ, Cox, AD

Proc. Natl. Acad. Sci. U.S.A. 1991
7991565 Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A

Ericsson, LH, Gelb, MH, Farnsworth, CC, Seabra, MC, Glomset, JA

Proc. Natl. Acad. Sci. U.S.A. 1994
8631982 Mechanism of digeranylgeranylation of Rab proteins. Formation of a complex between monogeranylgeranyl-Rab and Rab escort protein

Seabra, MC, Shen, F

J. Biol. Chem. 1996
11389151 Membrane targeting of a Rab GTPase that fails to associate with Rab escort protein (REP) or guanine nucleotide dissociation inhibitor (GDI)

Wilson, AL, Maltese, WA, Overmeyer, JH

J. Biol. Chem. 2001
8164745 Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange

Svejstrup, AB, Pfeffer, SR, Shapiro, AD, Soldati, T

Nature 1994
7957092 Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes

Seabra, MC, Steele-Mortimer, O, Horiuchi, H, Alexandrov, K, Zerial, M

EMBO J. 1994
17411337 Towards complete sets of farnesylated and geranylgeranylated proteins

Koranda, M, Maurer-Stroh, S, Sirota, FL, Eisenhaber, F, Schneider, G, Benetka, W

PLoS Comput. Biol. 2007
24023390 Large-scale top-down proteomics of the human proteome: membrane proteins, mitochondria, and senescence

Ahlf, DR, Kelleher, NL, Fellers, RT, Durbin, KR, Tran, JC, Early, BP, Thomas, PM, Catherman, AD

Mol. Cell Proteomics 2013
18532927 Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate

Seabra, MC, Baron, RA

Biochem. J. 2008
8349690 Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins

Kaibuchi, K, Alexandrov, K, Takai, Y, Ullrich, O, Huber, LA, Zerial, M, Sasaki, T, Stenmark, H

J. Biol. Chem. 1993
25341920 Rab proteins and the compartmentalization of the endosomal system

Wandinger-Ness, A, Zerial, M

Cold Spring Harb Perspect Biol 2014
17114793 Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation

Seabra, MC, Ali, BR, Leung, KF, Baron, R, Magee, AI

J. Biol. Chem. 2007
8375503 Isoprenylation of Rab proteins possessing a C-terminal CaaX motif

Joberty, G, Tavitian, A, Zahraoui, A

FEBS Lett. 1993
Catalyst Activity

geranyltranstransferase activity of RGGT:CHMs:RABs:GDP [cytosol]

Orthologous Events
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