HRD1/YOL013C Summary Help

Standard Name HRD1 1
Systematic Name YOL013C
Alias DER3 2
Feature Type ORF, Verified
Description Ubiquitin-protein ligase; functions in ER retention of misfolded proteins; required for ER-associated degradation (ERAD) of misfolded proteins; genetically linked to the unfolded protein response (UPR); regulated through association with Hrd3p; contains an H2 ring finger; likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the ER-localized translocon (1, 2, 3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description HMG-coA Reductase Degradation 1
Chromosomal Location
ChrXV:303035 to 301380 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All HRD1 GO evidence and references
  View Computational GO annotations for HRD1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 1 genes
Resources
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
overexpression
Resources
273 total interaction(s) for 122 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 58
  • Affinity Capture-Western: 43
  • Biochemical Activity: 11
  • PCA: 1
  • Reconstituted Complex: 11

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 4
  • Negative Genetic: 41
  • Phenotypic Enhancement: 25
  • Phenotypic Suppression: 42
  • Positive Genetic: 22
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 2
  • Synthetic Rescue: 5

Resources
Expression Summary
histogram
Resources
Length (a.a.) 551
Molecular Weight (Da) 63,534
Isoelectric Point (pI) 5.51
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:303035 to 301380 | 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..1656 303035..301380 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005373
SUMMARY PARAGRAPH for HRD1

Ssm4p and Hrd1p are ubiquitin ligases (E3) involved in endoplasmic reticulum-associated degradation (ERAD) (5, 4, 9). Ssm4p and Hrd1p are central members of the ubiquitin ligase complexes that are responsible for recognizing and ubiquitinating misfolded proteins in the ER for degradation by the proteasome (10, 11, 12). Misfolded cytosolic proteins are ubiquitinated by Ssm4p whereas misfolded luminal and membrane proteins are ubiquitinated by Hrd1p (10, 11, 12). The Ssm4p and Hrd1p ubiquitin ligase complexes also localize to different regions along the ER-nuclear membrane system: Ssm4p localizes to the inner nuclear membrane while Hrd1p remains in the ER membrane (13). Despite these differences, Ssm4p and Hrd1p appear to have overlapping substrate specificities and redundant functionalities (9, 14). Each ubiquitin ligase complex interacts with the Cdc48p-Npl4p-Ufd1p AAA ATPase complex via Ubx2p in order to extract ubiquitinated substrates from the ER (10, 11, 12, and references within).

Hrd1p forms a complex with Hrd3p, which stabilizes Hrd1p (6). Hrd3p also interacts with Kar2p and Yos9p to specifically target misfolded cytosolic proteins (10, 11, 12, and references within). Ubc7p or Ubc1p can act as the ubiquitin-conjugating enzyme (E2) for Hrd1p (5). Ubc7p interacts with the RING-H2 domain of Hrd1p (1, 4).

S. cerevisiae Hrd1p is related to the H. sapiens HRD1 and gp78, which is also known as the autocrine motility factor receptor (15 and references within). S. cerevisiae Hrd1p has also been shown to degrade the cystic fibrosis transmembrane conductance regulator (CFTR) when CFTR is expressed in yeast (16).

Last updated: 2008-02-11 Contact SGD

References cited on this page View Complete Literature Guide for HRD1
1) Hampton RY, et al.  (1996) Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell 7(12):2029-44
2) Bordallo J, et al.  (1998) Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol Biol Cell 9(1):209-22
3) Friedlander R, et al.  (2000) A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat Cell Biol 2(7):379-84
4) Deak PM and Wolf DH  (2001) Membrane topology and function of Der3/Hrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation. J Biol Chem 276(14):10663-9
5) Bays NW, et al.  (2001) Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat Cell Biol 3(1):24-9
6) Gardner RG, et al.  (2000) Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p. J Cell Biol 151(1):69-82
7) Rubenstein EM, et al.  (2012) Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase. J Cell Biol 197(6):761-73
8) Izawa T, et al.  (2012) Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation. Mol Biol Cell 23(7):1283-93
9) Swanson R, et al.  (2001) A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation. Genes Dev 15(20):2660-74
10) Gauss R, et al.  (2006) A complex of Yos9p and the HRD ligase integrates endoplasmic reticulum quality control into the degradation machinery. Nat Cell Biol 8(8):849-54
11) Denic V, et al.  (2006) A luminal surveillance complex that selects misfolded glycoproteins for ER-associated degradation. Cell 126(2):349-59
12) Carvalho P, et al.  (2006) Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell 126(2):361-73
13) Deng M and Hochstrasser M  (2006) Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligase. Nature 443(7113):827-31
14) Kota J, et al.  (2007) Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD. J Cell Biol 176(5):617-28
15) Kikkert M, et al.  (2004) Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem 279(5):3525-34
16) Gnann A, et al.  (2004) Cystic fibrosis transmembrane conductance regulator degradation depends on the lectins Htm1p/EDEM and the Cdc48 protein complex in yeast. Mol Biol Cell 15(9):4125-35