KAR2 Hsp70 family ATPase KAR2 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: KAR2
Gene description: Hsp70 family ATPase KAR2
Primary source: SGD:S000003571
Locus tag: YJL034W
See related: AllianceGenome:SGD:S000003571
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: GRP78
Summary: Enables ATP hydrolysis activity and unfolded protein binding activity. Involved in several processes, including fungal-type cell wall beta-glucan biosynthetic process; karyogamy involved in conjugation with cellular fusion; and protein targeting to ER. Located in endoplasmic reticulum. Part of luminal surveillance complex. Human ortholog(s) of this gene implicated in dopamine beta-hydroxylase deficiency. Orthologous to human HSPA5 (heat shock protein family A (Hsp70) member 5). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: X

Exon count:: 1

Sequence:: Chromosome: X; NC_001142.9 (381327..383375)

Chromosome X - NC_001142.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001142.9

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Reductive stress in the endoplasmic reticulum (ER) inhibits the Ost3-dependent N-glycosylation of Sil1, which regulates specific BiP functions appropriate to the needs of the ER under reductive stress.
Title: Diminished Ost3-dependent N-glycosylation of the BiP nucleotide exchange factor Sil1 is an adaptive response to reductive ER stress.
Here the authors demonstrate that BiP's nucleotide exchange factor - Sil1 - can reverse BiP cysteine oxidation.
Title: An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP.
Increased endoplasmic reticulum glutathione import triggers H2O2-dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop.
Title: Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip.
The authors found that the ATPase activity displayed by unmodified Kar2 is fully maintained when Cys63 is replaced with Ala or Val.
Title: A Conserved Cysteine within the ATPase Domain of the Endoplasmic Reticulum Chaperone BiP is Necessary for a Complete Complement of BiP Activities.
the susceptibility of BiP to modification with glutathione may serve also to prevent irreversible oxidation of BiP by peroxide.
Title: Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress.
Alteration of KAR2 (BiP) activity upon oxidation helps cells cope with disruption to oxidative folding within the endoplasmic reticulum during oxidative stress.
Title: Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress.
Coexpression of Kar2p, Pdi1p and Ero1p gave a synergistic effect on CPY expression
Title: Effects of signal sequences and folding accessory proteins on extracellular expression of carboxypeptidase Y in recombinant Saccharomyces cerevisiae.
Data indicate that BiP (GRP78/Kar2) stabilizes torsinA and torsinADeltaE in mammalian cells.
Title: The BiP molecular chaperone plays multiple roles during the biogenesis of torsinA, an AAA+ ATPase associated with the neurological disease early-onset torsion dystonia.
The inability to induce KAR2 under stress had no effect on its known housekeeping functions.
Title: Endoplasmic reticulum stress regulation of the Kar2p/BiP chaperone alleviates proteotoxicity via dual degradation pathways.
Kar2p mobility represents a powerful new tool capable of distinguishing between the different mechanisms leading to unfolded protein response activation in living cells.
Title: Kar2p availability defines distinct forms of endoplasmic reticulum stress in living cells.

Submit: New GeneRIF Correction See all GeneRIFs (18)

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 ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent protein folding chaperone	IEA Inferred from Electronic Annotation more info
enables heat shock protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables protein folding chaperone	IBA Inferred from Biological aspect of Ancestor more info
enables unfolded protein binding	IDA Inferred from Direct Assay more info	PubMed
enables unfolded protein binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in ERAD pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in SRP-dependent cotranslational protein targeting to membrane, translocation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chaperone cofactor-dependent protein refolding	IBA Inferred from Biological aspect of Ancestor more info
involved_in endoplasmic reticulum unfolded protein response	IBA Inferred from Biological aspect of Ancestor more info
involved_in fungal-type cell wall beta-glucan biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in karyogamy involved in conjugation with cellular fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in post-translational protein targeting to membrane, translocation	IDA Inferred from Direct Assay more info	PubMed
involved_in post-translational protein targeting to membrane, translocation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein refolding	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to unfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
part_of endoplasmic reticulum chaperone complex	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endoplasmic reticulum lumen	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum lumen	IEA Inferred from Electronic Annotation more info
part_of luminal surveillance complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: Hsp70 family ATPase KAR2

NP_012500.3

EC 3.6.4.10

ATPase involved in protein import into the ER; also acts as a chaperone to mediate protein folding in the ER and may play a role in ER export of soluble proteins; regulates the unfolded protein response via interaction with Ire1p