The reference OMIM entry for this protein is 179508

Ras-associated protein rab1; rab1
Rab1a

DESCRIPTION

The small GTPase RAB1 controls vesicle traffic from the endoplasmic reticulum (ER) to the Golgi apparatus. Rab1 belongs to the Ras superfamily of GTPases that cycle between inactive GDP-bound and active GTP-bound forms (Allan et al., 2000).

CLONING

From a human pheochromocytoma cDNA library, Zahraoui et al. (1989) isolated 7 cDNA clones corresponding to RAB genes, including RAB1. The predicted 205-amino acid human and rat RAB1 proteins are identical and share 75% identity with YPT1, the S. cerevisiae homolog. Northern blot analysis revealed that the RAB1 gene was expressed as a major (2.7 kb) and a minor (1.7 kb) mRNA in a human fibroblast cell line.

GENE FUNCTION

Using yeast 2-hybrid analysis and in vitro binding assays, Martincic et al. (1997) showed that rat Pra1 (RABAC1; 604925) bound prenylated Rab GTPases, including Rab3a (179490) and Rab1, but not other small Ras-like GTPases. Pra1 also interacted with the synaptic vesicle protein Vamp2 (185881), but not Vamp1 (185880) or cellubrevin (VAMP3; 603657). Deletion analysis showed that both an N-terminal region spanning amino acids 30 to 54 and the extreme C-terminal domain of Pra1 were required for binding both Rab GTPases and Vamp1. Martincic et al. (1997) suggested that PRA1 may link Rab proteins and VAMP2 in the control of vesicle docking and fusion. Allan et al. (2000) demonstrated that the tethering factor p115 (603344) is a RAB1 effector that binds directly to activated RAB1. RAB1 recruited p115 to coat protein complex II (COPII; see 601924) vesicles during budding from the endoplasmic reticulum (ER), where it interacted with a select set of COPII vesicle-associated SNAREs (see 603215) to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. Allan et al. (2000) proposed that RAB1-regulated assembly of functional effector-SNARE complexes defines a conserved molecular mechanism to coordinate recognition between subcellular compartments. Cooper et al. (2006) found that the earliest defect following alpha-synuclein (163890) expression in yeast was a block in ER-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphate Ypt1p, which associated with cytoplasmic alpha-synuclein inclusions. Elevated expression of Rab1, the mammalian Ypt1 homolog, protected against alpha-synuclein-induced dopaminergic neuron loss in animal models of Parkinson disease (168600). Thus, Cooper et al. (2006) concluded that synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable. Legionella pneumophila replicates in cellular vacuoles that recruit material from the host cell ER. Vacuole development depends on translocation of secreted bacterial proteins across host cell membranes. Using binding assays and immunofluorescence microscopy, Machner and Isberg (2006) found that the translocated protein SidM targeted host cell RAB1. Acting as guanosine nucleotide exchange factor, SidM recruited RAB1 to Legionella-containing vacuoles, and this process was enhanced by bacterial LidA. Expression of SidM in mammalian cells interfered with the secretory pathway and caused Golgi fragmentation. Machner and Isberg (2006) proposed that SidM and LidA mimic host factors involved in ER-derived vesicle trafficking and may facilitate ve ... More on the omim web site

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July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 179508 was added.