HRD1 E3 ubiquitin-protein ligase HRD1 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: HRD1
Official Full Name: E3 ubiquitin-protein ligase HRD1
Primary source: SGD:S000005373
Locus tag: YOL013C
See related: AllianceGenome:SGD:S000005373; FungiDB:YOL013C; VEuPathDB:YOL013C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: DER3
Summary: Enables ubiquitin-protein transferase activity. Involved in several processes, including endoplasmic reticulum unfolded protein response; protein autoubiquitination; and retrograde protein transport, ER to cytosol. Located in endoplasmic reticulum membrane. Part of Hrd1p ubiquitin ligase ERAD-L complex and Hrd1p ubiquitin ligase ERAD-M complex. Used to study alpha 1-antitrypsin deficiency. Orthologous to human SYVN1 (synoviolin 1). [provided by Alliance of Genome Resources, Nov 2024]
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Genomic context

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See HRD1 in Genome Data Viewer

Location:: chromosome: XV

Exon count:: 1

Sequence:: Chromosome: XV; NC_001147.6 (301380..303035, complement)

Chromosome XV - NC_001147.6 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001147.6

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.
Title: Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.
Disulfide-crosslink analysis of the ubiquitin ligase Hrd1 complex during endoplasmic reticulum-associated protein degradation.
Title: Disulfide-crosslink analysis of the ubiquitin ligase Hrd1 complex during endoplasmic reticulum-associated protein degradation.
Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.
Title: Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.
Identification of two binding sites for misfolded proteins in Hrd1, a low-affinity luminal site and a high-affinity cytoplasmic site formed following auto-ubiquitination of specific lysine residues in Hrd1's RING domain. The affinity difference between the luminal and cytoplasmic binding sites may provide the initial driving force for substrate movement through Hrd1.
Title: Hrd1 forms the retrotranslocation pore regulated by auto-ubiquitination and binding of misfolded proteins.
cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3: results suggest that Hrd1 forms a retro-translocation channel for the movement of misfolded polypeptides through the endoplasmic reticulum membrane
Title: Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3.
Authors reconstituted retrotranslocation with purified S. cerevisiae proteins, using proteoliposomes containing the multi-spanning ubiquitin ligase Hrd1. Retrotranslocation of the luminal domain of a membrane-spanning substrate is triggered by autoubiquitination of Hrd1.
Title: Autoubiquitination of the Hrd1 Ligase Triggers Protein Retrotranslocation in ERAD.
Data indicate that N-terminal acetylation of Der1 regulates its degradation by the Hrd1 ligase.
Title: N-terminal acetylation of the yeast Derlin Der1 is essential for Hrd1 ubiquitin-ligase activity toward luminal ER substrates.
Cytosolic entry of Shiga-like toxin a chain from the yeast endoplasmic reticulum requires catalytically active Hrd1p.
Title: Cytosolic entry of Shiga-like toxin a chain from the yeast endoplasmic reticulum requires catalytically active Hrd1p.
Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon.
Title: Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase.
Yos9p and Hrd1p mediate ER retention of misfolded proteins in the early stage of ERAD, which constitutes a process separable from the later degradation step.
Title: Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables ubiquitin-protein transferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	RCA inferred from Reviewed Computational Analysis more info	PubMed

Process	Evidence Code	Pubs
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fungal-type cell wall organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in proteolysis involved in protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in retrograde protein transport, ER to cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in retrograde protein transport, ER to cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of Hrd1p ubiquitin ligase ERAD-L complex	IDA Inferred from Direct Assay more info	PubMed
part_of Hrd1p ubiquitin ligase ERAD-M complex	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: E3 ubiquitin-protein ligase HRD1

NP_014630.1

EC 2.3.2.27

Ubiquitin-protein ligase involved in ER-associated degradation (ERAD) of misfolded proteins; upon autoubiquitination triggers retrotranslocation of misfolded proteins to cytosol for degradation; 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

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001147.6 Reference assembly

Range

301380..303035 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001183267.1 → NP_014630.1 TPA: E3 ubiquitin-protein ligase HRD1 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_014630.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6W254, Q08109

UniProtKB/TrEMBL

B3LJ43, B5VRP1, C8ZHV2, N1NWS6

Conserved Domains (1) summary

COG5243
Location:5 → 551

HRD1; HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones]