High impact information on VPS9

• Mechanism of ubiquitin recognition by the CUE domain of Vps9p [1].
• The region required for monoubiquitin binding mapped to the Vps9 CUE domain, a sequence previously identified by database searches as similar to parts of the yeast Cue1 and mammalian Tollip proteins [2].
• We have cloned VPS9 by complementation of the vacuolar protein sorting defect of vps9 cells, characterized its gene product, and investigated its role in vacuolar protein sorting [3].
• Analysis of the VPS9 DNA sequence predicts that Vps9p is related to human proteins that bind Ras and negatively regulate Ras-mediated signaling [3].
• Ubiquitin signals protein trafficking via interaction with a novel ubiquitin binding domain in the membrane fusion regulator, Vps9p [4].

Biological context of VPS9

• Vps9p ubiquitin binding is required for efficient endocytosis of Ste3p but not for the delivery of the biosynthetic cargo carboxypeptidase Y to the vacuole [5].
• However, Vps9p did not stimulate guanine nucleotide exchange of GTP-bound Vps21p or GTP hydrolysis [6].

Associations of VPS9 with chemical compounds

• Vps9p is a guanine nucleotide exchange factor involved in vesicle-mediated vacuolar protein transport [6].

Physical interactions of VPS9

• We thus provide evidence for biochemical and genetic interactions between Ub and a novel Ub binding domain in Vps9p [4].

Regulatory relationships of VPS9

• This block resembled that of a receptor fused to wild-type Ub but expressed in a vps9-null background [4].
• The yeast Rab5 ortholog Vps21p is activated by its guanine nucleotide exchange factor Vps9p [5].

Other interactions of VPS9

• Overexpression of VPS9, BTS1 and OKP1 suppressed the carboxypeptidase Y secretion defect of deltabph1 [7].
• Vps9, Rabex-5 and DSS4: proteins with weak but distinct nucleotide-exchange activities for Rab proteins [8].
• Vps9p, which promotes endosomal and Golgi-derived vesicle fusion, binds directly to Ub via a Cue1p-homologous (CUE) domain [4].
• The activities of three Rab-specific factors with GDP/GTP exchange activity, Vps9p, Rabex-5 and DSS4, with their cognate GTPases, Ypt51p, Rab5 and Ypt1p, have been analysed quantitatively [8].

Analytical, diagnostic and therapeutic context of VPS9

• Antibodies raised against Vps9p immunoprecipitate a rare 52-kDa protein that fractionates with cytosolic proteins following cell lysis and centrifugation [3].
• Using both yeast two-hybrid assays and chemical cross-linking, we have identified another VPS gene product, Vps9p, that preferentially interacts with a mutant form of Vps21p-S21N that binds GDP but not GTP [6].

References