DID4/YKL002W Summary Help

Standard Name DID4 1
Systematic Name YKL002W
Alias GRD7 2 , REN1 3 , VPL2 4 , VPT14 5 , VPS2 5 , 6 , CHM2 7 , VPS14 8
Feature Type ORF, Verified
Description Class E Vps protein of the ESCRT-III complex; required for sorting of integral membrane proteins into lumenal vesicles of multivesicular bodies, and for delivery of newly synthesized vacuolar enzymes to the vacuole, involved in endocytosis (1, 3, 9, 10 and see Summary Paragraph)
Name Description Doa4-Independent Degradation 1
Chromosomal Location
ChrXI:437778 to 438544 | ORF Map | GBrowse
Gene Ontology Annotations All DID4 GO evidence and references
  View Computational GO annotations for DID4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Classical genetics
reduction of function
Large-scale survey
120 total interaction(s) for 101 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 7
  • Co-crystal Structure: 1
  • Co-localization: 1
  • Far Western: 1
  • FRET: 1
  • PCA: 4
  • Reconstituted Complex: 2
  • Two-hybrid: 12

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 55
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 2
  • Positive Genetic: 8
  • Synthetic Growth Defect: 10
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 1
  • Synthetic Rescue: 4

Expression Summary
Length (a.a.) 232
Molecular Weight (Da) 26,291
Isoelectric Point (pI) 5.06
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:437778 to 438544 | ORF Map | GBrowse
This feature contains embedded feature(s): YKL003W-A
Last Update Coordinates: 2011-02-03 | Sequence: 2000-07-22
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..60 437778..437837 2011-02-03 2000-07-22
Intron 61..128 437838..437905 2011-02-03 2000-07-22
CDS 129..767 437906..438544 2011-02-03 2000-07-22
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 SGDIDS000001485

Most proteins targeted for degradation in the multivesicular body (MVB) pathway are monoubiquitinated, then passed through the series of highly-conserved multisubunit complexes known as ESCRT (Endosomal Sorting Complex Required for Transport). 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 (11).

The formation of ESCRT III - composed of subcomplexes Snf7p-Vps20p and Did4p-Vps24p - is transient and appears to be dependent on ESCRT II (12, 9). Snf7p-Vps20p effects the membrane association of ESCRT III, with Snf7p being required for localization of the Bro1p vacuolar protein sorting factor to endosomes (10, 13), and Vps20p for formation of ESCRT III (14, 9). The Did4p-Vps24p subcomplex is required for endosomal localization of the Doa4p ubiquitin hydrolase, as well as the Vps4p AAA-type ATPase, which is necessary for the dissociation of ESCRT III (9, 1, 12, 15, 16, 11).

did4 null mutants display growth defects at high temperatures, as well as increased sensitivity to manganese ions. Overproduction of Did4p suppresses the high temperature and canavanine sensitivities of vps24 null mutants (17, 1).

Last updated: 2006-03-13 Contact SGD

References cited on this page View Complete Literature Guide for DID4
1) Amerik AY, et al.  (2000) The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell 11(10):3365-80
2) 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
3) Davis NG, et al.  (1993) Cis- and trans-acting functions required for endocytosis of the yeast pheromone receptors. J Cell Biol 122(1):53-65
4) Rothman JH and Stevens TH  (1986) Protein sorting in yeast: mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway. Cell 47(6):1041-51
5) 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
6) 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
7) Howard TL, et al.  (2001) CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. J Cell Sci 114(Pt 13):2395-404
8) Raymond CK, et al.  (1992) Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell 3(12):1389-402
9) Babst M, et al.  (2002) Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3(2):271-82
10) Odorizzi G, et al.  (2003) Bro1 is an endosome-associated protein that functions in the MVB pathway in Saccharomyces cerevisiae. J Cell Sci 116(Pt 10):1893-903
11) 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
12) 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
13) 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
14) Ashrafi K, et al.  (1998) A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J Biol Chem 273(40):25864-74
15) Yeo SC, et al.  (2003) Vps20p and Vta1p interact with Vps4p and function in multivesicular body sorting and endosomal transport in Saccharomyces cerevisiae. J Cell Sci 116(Pt 19):3957-70
16) Bowers K, et al.  (2004) Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic 5(3):194-210
17) Eguez L, et al.  (2004) Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics 167(1):107-17