NPL4/YBR170C Summary Help

Standard Name NPL4 1
Systematic Name YBR170C
Alias HRD4
Feature Type ORF, Verified
Description Substrate-recruiting cofactor of the Cdc48p-Npl4p-Ufd1p segregase; assists Cdc48p in the dislocation of misfolded, polyubiquitinated ERAD substrates that are subsequently delivered to the proteasome for degradation; also involved in the regulated destruction of resident ER membrane proteins, such as HMG-CoA reductase (Hmg1/2p) and cytoplasmic proteins (Fbp1p); role in mobilizing membrane bound transcription factors by regulated ubiquitin/proteasome-dependent processing (RUP) (2, 3, 4, 5, 6, 7)
Name Description Nuclear Protein Localization 1
Chromosomal Location
ChrII:578086 to 576344 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All NPL4 GO evidence and references
  View Computational GO annotations for NPL4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Classical genetics
Large-scale survey
119 total interaction(s) for 49 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 42
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 22
  • Biochemical Activity: 2
  • Co-purification: 3
  • Reconstituted Complex: 8
  • Two-hybrid: 5

Genetic Interactions
  • Dosage Rescue: 5
  • Negative Genetic: 1
  • Phenotypic Suppression: 4
  • Positive Genetic: 1
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 5
  • Synthetic Rescue: 16

Expression Summary
Length (a.a.) 580
Molecular Weight (Da) 65,782
Isoelectric Point (pI) 5.57
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrII:578086 to 576344 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1743 578086..576344 2011-02-03 1997-01-28
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 SGDIDS000000374
References cited on this page View Complete Literature Guide for NPL4
1) Bossie MA, et al.  (1992) A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast. Mol Biol Cell 3(8):875-93
2) Hitchcock AL, et al.  (2001) The conserved npl4 protein complex mediates proteasome-dependent membrane-bound transcription factor activation. Mol Biol Cell 12(10):3226-41
3) Bays NW, et al.  (2001) HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins. Mol Biol Cell 12(12):4114-28
4) Ye Y, et al.  (2003) Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains. J Cell Biol 162(1):71-84
5) Rape M, et al.  (2001) Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 107(5):667-77
6) Barbin L, et al.  (2010) The Cdc48-Ufd1-Npl4 complex is central in ubiquitin-proteasome triggered catabolite degradation of fructose-1,6-bisphosphatase. Biochem Biophys Res Commun 394(2):335-41
7) Heo JM, et al.  (2010) A stress-responsive system for mitochondrial protein degradation. Mol Cell 40(3):465-80