VPS25/YJR102C Summary Help

Standard Name VPS25 1, 2, 3
Systematic Name YJR102C
Alias VPT25 1 , VPL12 2
Feature Type ORF, Verified
Description Component of the ESCRT-II complex; ESCRT-II is involved in ubiquitin-dependent sorting of proteins into the endosome (4 and see Summary Paragraph)
Name Description Vacuolar Protein Sorting 1, 2
Chromosomal Location
ChrX:619765 to 619157 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All VPS25 GO evidence and references
  View Computational GO annotations for VPS25
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
null
overexpression
reduction of function
Large-scale survey
null
Resources
72 total interaction(s) for 56 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 1
  • Co-crystal Structure: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 14

Genetic Interactions
  • Dosage Lethality: 1
  • Negative Genetic: 11
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 2
  • Synthetic Growth Defect: 21
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 11
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 202
Molecular Weight (Da) 23,557
Isoelectric Point (pI) 5.17
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:619765 to 619157 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..609 619765..619157 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003863
SUMMARY PARAGRAPH for VPS25

Most proteins targeted for degradation in the multivesicular body (MVB) pathway are monoubiquitinated, then passed through the ESCRT complexes (Endosomal Sorting Complex Required for Transport), a series of highly-conserved multisubunit complexes. ESCRT I, II, and III are sequentially mobilized to endosomal membranes, where they direct protein sorting and MVB biogenesis, and play a crucial role in retrovirus budding (5).

ESCRT II (composed of Snf8p, Vps25p, and Vps36p) is a 155-kDa trilobal cytoplasmic complex that transiently associates with endosomes and appears to regulate the formation of ESCRT III (Did4p, Snf7p, Vps20p and Vps24p) (3). The ESCRT II core, which contains two copies of Vps25p, one copy of Snf8p, and the C-terminal region of Vps36p, consists of eight repeats of a common building block, a "winged helix" domain. Two PPXY-motifs from Vps25p are involved in contacts with Snf8p and Vps36p, and their mutation leads to disruption of the complex (5). Each ESCRT II subunit binds the other two subunits of ESCRT II, as well as Vps28p of ESCRT I and Vps20p of ESCRT III, with Vps25p being the main subunit responsible for the interaction with Vps20p (6, 5). Vps36p also binds ubiquitinated target proteins (4).

Null mutants in SNF8, VPS25, or VPS36 are extremely sensitive to calcium, lithium or manganese ions, and to high temperatures (7). These mutants also display mislocalization of Rim20p to a few large perivacuolar foci, suggesting that ESCRT II is involved in regulating Rim20p localization (8). snf8, vps20 or vps36 nulls also accumulate Fur4p at the plasma membrane, which increases uptake of 5-fluorouracil (5-FU), a toxic analog of uracil (9).

The human homologs of the ESCRT II proteins interact with one another, with human Vps20p (a component of ESCRT III) and with their yeast homologs. siRNA depletion of mammalian ESCRT II does not affect degradation of epidermal growth factor, a known cargo of the multivesicular body protein sorting pathway, suggesting that mammalian ESCRT II may be redundant, cargo-specific, or not required for protein sorting at the multivesicular body (10, 11, 12).

In addition to vacuolar protein sorting defects, vps25 null mutants display increased sensitivity to the antifungal agent caspofungin, which interferes with glucan synthesis and cell wall formation (13). vps25 nulls also display a reduced frequency of Rim20p-GFP foci under alkaline conditions as compared to wild type (8).

VPS25 has homologs in mouse, human, and fission yeast, and is similar to Drosophila melanogaster l(2)44Db and Caenorhabditis elegans W02A11.2 (10).

Last updated: 2006-02-08 Contact SGD

References cited on this page View Complete Literature Guide for VPS25
1) Robinson JS, et al.  (1988) Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol 8(11):4936-48
2) Rothman JH, et al.  (1989) Characterization of genes required for protein sorting and vacuolar function in the yeast Saccharomyces cerevisiae. EMBO J 8(7):2057-65
3) Babst M, et al.  (2002) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3(2):283-9
4) Hierro A, et al.  (2004) Structure of the ESCRT-II endosomal trafficking complex. Nature 431(7005):221-5
5) Teo H, et al.  (2004) ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes. Dev Cell 7(4):559-69
6) Bowers K and Stevens TH  (2005) Protein transport from the late Golgi to the vacuole in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1744(3):438-54
7) Eguez L, et al.  (2004) Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics 167(1):107-17
8) Boysen JH and Mitchell AP  (2006) Control of Bro1-domain protein Rim20 localization by external pH, ESCRT machinery, and the Saccharomyces cerevisiae Rim101 pathway. Mol Biol Cell 17(3):1344-53
9) Bugnicourt A, et al.  (2004) Antagonistic roles of ESCRT and Vps class C/HOPS complexes in the recycling of yeast membrane proteins. Mol Biol Cell 15(9):4203-14
10) Kamura T, et al.  (2001) Cloning and characterization of ELL-associated proteins EAP45 and EAP20. a role for yeast EAP-like proteins in regulation of gene expression by glucose. J Biol Chem 276(19):16528-33
11) Raiborg C, et al.  (2003) Protein sorting into multivesicular endosomes. Curr Opin Cell Biol 15(4):446-55
12) Bowers K, et al.  (2006) Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII. J Biol Chem 281(8):5094-105
13) Markovich S, et al.  (2004) Genomic approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces cerevisiae. Antimicrob Agents Chemother 48(10):3871-6