HSC82/YMR186W Summary Help

Standard Name HSC82 1
Systematic Name YMR186W
Alias HSP90 2
Feature Type ORF, Verified
Description Cytoplasmic chaperone of the Hsp90 family; plays a role in determining prion variants; redundant in function and nearly identical with Hsp82p, and together they are essential; expressed constitutively at 10-fold higher basal levels than HSP82 and induced 2-3 fold by heat shock; contains two acid-rich unstructured regions that promote the solubility of chaperone-substrate complexes; HSC82 has a paralog, HSP82, that arose from the whole genome duplication (2, 3, 4, 5, 6 and see Summary Paragraph)
Chromosomal Location
ChrXIII:632355 to 634472 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All HSC82 GO evidence and references
  View Computational GO annotations for HSC82
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 17 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
repressible
Resources
1273 total interaction(s) for 1040 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 177
  • Affinity Capture-RNA: 7
  • Affinity Capture-Western: 27
  • Biochemical Activity: 1
  • Co-crystal Structure: 3
  • FRET: 2
  • PCA: 2
  • Protein-peptide: 1
  • Reconstituted Complex: 11
  • Two-hybrid: 5

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Rescue: 11
  • Negative Genetic: 27
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 7
  • Positive Genetic: 4
  • Synthetic Growth Defect: 967
  • Synthetic Lethality: 14
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 705
Molecular Weight (Da) 80,899
Isoelectric Point (pI) 4.59
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:632355 to 634472 | ORF Map | GBrowse
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..2118 632355..634472 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004798
SUMMARY PARAGRAPH for HSC82

In S. cerevisiae, the molecular chaperone HSP90 exists as two isoforms, encoded by the genes HSC82 and HSP82 (3). HSP90 family member activity is required for folding a specific set of difficult-to-fold proteins from nascent polypeptides into biologically active structures as well as for the refolding of denatured proteins back into native conformations (7). Although most cellular proteins do not require Hsp82p/Hsc82p chaperone activity for correct folding under normal conditions, Hsp82p and Hsc82p are required for the activation of many key cellular regulatory and signaling proteins, like kinases and transcription factors, such as Swe1p, Gcn2p, and Hap1p (reviewed in 8, 9, and 10).

HSP82 and HSC82 share ~97% sequence identity and together, the encoded proteins comprise 1-2% of all the protein in the cytosol. While HSC82 is expressed constitutively at high levels and only slightly induced by heat shock, HSP82 transcription is strongly induced by both heat and stress (3).

All members of the HSP90 family function as dimers and protein folding is driven by the ATPase activity of the chaperone (11). Binding of ATP to the Hsp82p/Hsc82p N-terminus induces conformational changes in the protein as well as transient dimerization of the N-terminal nucleotide-binding domain (12, 13, 14 and references contained therein). Studies of the mammalian homolog show that Hsp82p and Hsc82p also contain a second ATP-binding site in the C-terminus that only forms after a conformational change is induced by occupancy of the N-terminal ATP binding site (15, 16).

Hsp82p and Hsc82p associate with many co-chaperones which both positively and negatively regulate Hsp82p/Hsc82p function. Hsp82p/Hsc82p co-chaperones include Sti1p, Cdc37p, Cns1p, Sba1p, Cpr6p, Cpr7p, Sse1p, Hch1p, and Aha1p (17 and references therein and reviewed in 8). One common method by which these partner proteins regulate Hsp82p/Hsc82p activity is through the inhibition/enhancement of ATP hydrolysis. Mechanistically, this can occur through direct interference of ATP binding or by alteration of Hsp82p/Hsc82p protein conformation such that ATP binding is affected (18, 19).

HSP82 and HSC82 are highly conserved among eukaryotes and the presence of at least one of the HSP90 gene product family members is essential for viability in yeast, Drosophila, and humans (7 and references therein). Overexpression of HSP82 in S. cerevisiae has been shown to increase the virulence of the yeast in mice (20). Human HSP90 (OMIM and OMIM) is being explored as a target for cancer therapeutics due to its role in folding oncogenic protein kinases and because inhibition of chaperone activity by ATP analogs has been shown to promote substrate protein degradation via the ubiquitin-dependent proteasomal pathway (21, 22, 23).

Last updated: 2006-06-12 Contact SGD

References cited on this page View Complete Literature Guide for HSC82
1) Gross, D.S.  (1992) Personal Communication, Mortimer Map Edition 11
2) Gross DS, et al.  (1990) Promoter function and in situ protein/DNA interactions upstream of the yeast HSP90 heat shock genes. Antonie Van Leeuwenhoek 58(3):175-86
3) Borkovich KA, et al.  (1989) hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures. Mol Cell Biol 9(9):3919-30
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Pursell NW, et al.  (2012) Solubility-promoting function of Hsp90 contributes to client maturation and robust cell growth. Eukaryot Cell 11(8):1033-41
6) Lancaster DL, et al.  (2013) Chaperone proteins select and maintain [PIN+] prion conformations in Saccharomyces cerevisiae. J Biol Chem 288(2):1266-76
7) Nathan DF, et al.  (1997) In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci U S A 94(24):12949-56
8) Burnie JP, et al.  (2006) Fungal heat-shock proteins in human disease. FEMS Microbiol Rev 30(1):53-88
9) Picard D  (2002) Heat-shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci 59(10):1640-8
10) Prodromou C and Pearl LH  (2003) Structure and functional relationships of Hsp90. Curr Cancer Drug Targets 3(5):301-23
11) Richter K, et al.  (2001) Coordinated ATP hydrolysis by the Hsp90 dimer. J Biol Chem 276(36):33689-96
12) Prodromou C, et al.  (2000) The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains. EMBO J 19(16):4383-92
13) Ali MM, et al.  (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440(7087):1013-7
14) Richter K, et al.  (2006) Intrinsic inhibition of the Hsp90 ATPase activity. J Biol Chem 281(16):11301-11
15) Soti C, et al.  (2002) A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J Biol Chem 277(9):7066-75
16) Garnier C, et al.  (2002) Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain. J Biol Chem 277(14):12208-14
17) Millson SH, et al.  (2004) Investigating the protein-protein interactions of the yeast Hsp90 chaperone system by two-hybrid analysis: potential uses and limitations of this approach. Cell Stress Chaperones 9(4):359-68
18) Prodromou C, et al.  (1999) Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO J 18(3):754-62
19) Panaretou B, et al.  (2002) Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol Cell 10(6):1307-18
20) Hodgetts S, et al.  (1996) Over-expression of Saccharomyces cerevisiae hsp90 enhances the virulence of this yeast in mice. FEMS Immunol Med Microbiol 16(3-4):229-34
21) Workman P  (2004) Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Lett 206(2):149-57
22) Mimnaugh EG, et al.  (1996) Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem 271(37):22796-801
23) Pearl LH  (2005) Hsp90 and Cdc37 -- a chaperone cancer conspiracy. Curr Opin Genet Dev 15(1):55-61