VPS36/YLR417W Summary Help

Standard Name VPS36 1, 2
Systematic Name YLR417W
Alias GRD12 3 , VAC3 4 , VPL11 2
Feature Type ORF, Verified
Description Component of the ESCRT-II complex; contains the GLUE (GRAM Like Ubiquitin binding in EAP45) domain which is involved in interactions with ESCRT-I and ubiquitin-dependent sorting of proteins into the endosome; plays a role in the formation of mutant huntingtin (Htt) aggregates in yeast (5, 6, 7 and see Summary Paragraph)
Name Description Vacuolar Protein Sorting 1, 2
Chromosomal Location
ChrXII:955010 to 956710 | ORF Map | GBrowse
Gene Ontology Annotations All VPS36 GO evidence and references
  View Computational GO annotations for VPS36
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 7 genes
Classical genetics
reduction of function
Large-scale survey
95 total interaction(s) for 71 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-Western: 4
  • Co-crystal Structure: 3
  • Co-purification: 1
  • Two-hybrid: 20

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Negative Genetic: 12
  • Phenotypic Enhancement: 6
  • Phenotypic Suppression: 2
  • Positive Genetic: 1
  • Synthetic Growth Defect: 23
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 12
  • Synthetic Rescue: 4

Expression Summary
Length (a.a.) 566
Molecular Weight (Da) 64,017
Isoelectric Point (pI) 6.31
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:955010 to 956710 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1701 955010..956710 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004409

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 (8).

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) (9). 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 (8). 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 (10, 8). Vps36p also binds ubiquitinated target proteins (5).

Null mutants in SNF8, VPS25, or VPS36 are extremely sensitive to calcium, lithium or manganese ions, and to high temperatures (11). These mutants also display mislocalization of Rim20p to a few large perivacuolar foci, suggesting that ESCRT II is involved in regulating Rim20p localization (12). 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 (13).

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 (14, 15, 16).

Vps36p contains two zinc-finger motifs in its N-terminus, the second of which binds ubiquitin and is thought to be the main site of interaction between ESCRT II and ubiquitinated target proteins (5, 15, 17). In addition to being isolated in a search for vacuolar protein sorting (vps) mutants, VPS36 has been isolated in searches for mutants defective in retention of late-Golgi membrane proteins and repression of DIT1 and DIT2 transcription, which depends on activated Rim101p (18).

Vps36p has homologs in mouse, human, and fission yeast, and is similar to Drosophila melanogaster CG10711 and Caenorhabditis elegans F17C11.8 (14, 17).

Last updated: 2006-02-08 Contact SGD

References cited on this page View Complete Literature Guide for VPS36
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) Nothwehr SF, et al.  (1996) The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins. Mol Cell Biol 16(6):2700-7
4) Bowers K, et al.  (2000) The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae. Mol Biol Cell 11(12):4277-94
5) Hierro A, et al.  (2004) Structure of the ESCRT-II endosomal trafficking complex. Nature 431(7005):221-5
6) Teo H, et al.  (2006) ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. Cell 125(1):99-111
7) Verma M, et al.  (2012) Curcumin Prevents Formation of Polyglutamine Aggregates by Inhibiting Vps36, a Component of the ESCRT-II Complex. PLoS One 7(8):e42923
8) 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
9) 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
10) 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
11) Eguez L, et al.  (2004) Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics 167(1):107-17
12) 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
13) 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
14) 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
15) Raiborg C, et al.  (2003) Protein sorting into multivesicular endosomes. Curr Opin Cell Biol 15(4):446-55
16) 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
17) Slagsvold T, et al.  (2005) Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J Biol Chem 280(20):19600-6
18) Rothfels K, et al.  (2005) Components of the ESCRT pathway, DFG16, and YGR122w are required for Rim101 to act as a corepressor with Nrg1 at the negative regulatory element of the DIT1 gene of Saccharomyces cerevisiae. Mol Cell Biol 25(15):6772-88