LHS1/YKL073W Summary Help

Standard Name LHS1 1
Systematic Name YKL073W
Alias CER1 , SSI1
Feature Type ORF, Verified
Description Molecular chaperone of the endoplasmic reticulum lumen; involved in polypeptide translocation and folding; nucleotide exchange factor for the ER lumenal Hsp70 chaperone Kar2p; regulated by the unfolded protein response pathway (1, 2, 3, 4 and see Summary Paragraph)
Name Description Lumenal Hsp Seventy 1
Chromosomal Location
ChrXI:296430 to 299075 | ORF Map | GBrowse
Gene Ontology Annotations All LHS1 GO evidence and references
  View Computational GO annotations for LHS1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Classical genetics
Large-scale survey
254 total interaction(s) for 139 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 10
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 6
  • Biochemical Activity: 2
  • PCA: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 20

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 3
  • Negative Genetic: 78
  • Phenotypic Enhancement: 17
  • Phenotypic Suppression: 56
  • Positive Genetic: 45
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 7

Expression Summary
Length (a.a.) 881
Molecular Weight (Da) 99,571
Isoelectric Point (pI) 5.04
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:296430 to 299075 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2646 296430..299075 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001556

LHS1 encodes a non-essential protein with sequence similarity to the HSP70 family of molecular chaperones (5). HSP70 is a large family of proteins that has been evolutionarily conserved from bacteria (DnaK) to humans (HSP72/73). HSP70 proteins were originally classified based upon their induction by heat shock and their size of ~70kDa (reviewed in 6). S. cerevisiae has at least 9 cytosolic forms of HSP70 (encoded by SSA1, SSA2, SSA3, SSA4, SSB1, SSB2, SSE1, SSE2, SSZ1), 2 HSP70s which are found in the endoplasmic reticulum (KAR2, LHS1), and 3 mitochondrial HSP70 proteins (SSC1, SSQ1, ECM10).

Lhs1p localizes to the ER and shares 24% amino acid identity with the other ER HSP70 protein, Kar2p (2). These two proteins reciprocally regulate each other; the ATPase activity of Lhs1p is stimulated by Kar2p and Lhs1p enhances the rate of Kar2p ATP turnover by providing specific nucleotide exchange (4). While Kar2p is involved in both co- and post-translational targeting of proteins into the ER, Lhs1p only participates in post-translational import (3). In addition, Lhs1p activity also affects the refolding and stability of heat-denatured proteins (7).

LHS1 expression is induced by the drug tunicamycin and also by conditions that lead to the accumulation of unfolded proteins and triggering of the Unfolded Protein Response (UPR) (2, 1). Upregulation of LHS1 expression during UPR is mediated by the transcriptional activator Hac1p, which binds a 22 base pair UPR element, containing the consensus sequence 5'-CAGCGTG-3', present in the LHS1 promoter (8, 2). lhs1 null mutations result in cold sensitivity, enhanced resistance to manganese, a partial block in ER protein translocation, and constitutive activation of UPR (2, 1).

Last updated: 2006-02-12 Contact SGD

References cited on this page View Complete Literature Guide for LHS1
1) Craven RA, et al.  (1996) A novel Hsp70 of the yeast ER lumen is required for the efficient translocation of a number of protein precursors. EMBO J 15(11):2640-50
2) Baxter BK, et al.  (1996) SSI1 encodes a novel Hsp70 of the Saccharomyces cerevisiae endoplasmic reticulum. Mol Cell Biol 16(11):6444-56
3) Hamilton TG and Flynn GC  (1996) Cer1p, a novel Hsp70-related protein required for posttranslational endoplasmic reticulum translocation in yeast. J Biol Chem 271(48):30610-3
4) Steel GJ, et al.  (2004) Coordinated activation of Hsp70 chaperones. Science 303(5654):98-101
5) Hallstrom TC, et al.  (1998) Regulation of transcription factor Pdr1p function by an Hsp70 protein in Saccharomyces cerevisiae. Mol Cell Biol 18(3):1147-55
6) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
7) Saris N, et al.  (1997) The Hsp70 homologue Lhs1p is involved in a novel function of the yeast endoplasmic reticulum, refolding and stabilization of heat-denatured protein aggregates. J Cell Biol 137(4):813-24
8) Mori K, et al.  (1998) Palindrome with spacer of one nucleotide is characteristic of the cis-acting unfolded protein response element in Saccharomyces cerevisiae. J Biol Chem 273(16):9912-20