SSA1/YAL005C Summary Help

Standard Name SSA1 1
Systematic Name YAL005C
Alias YG100 2
Feature Type ORF, Verified
Description ATPase involved in protein folding and NLS-directed nuclear transport; member of HSP70 family; forms chaperone complex with Ydj1p; localized to nucleus, cytoplasm, and cell wall; 98% identical with paralog Ssa2p, but subtle differences between the two proteins provide functional specificity with respect to propagation of yeast [URE3] prions and vacuolar-mediated degradations of gluconeogenesis enzymes; general targeting factor of Hsp104p to prion fibrils (3, 4, 5, 6, 7, 8, 9 and see Summary Paragraph)
Name Description Stress-Seventy subfamily A
Chromosomal Location
ChrI:141431 to 139503 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -1 cM
Gene Ontology Annotations All SSA1 GO evidence and references
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 14 genes
Resources
Classical genetics
conditional
dominant negative
null
overexpression
reduction of function
Large-scale survey
null
Resources
821 total interaction(s) for 529 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 651
  • Affinity Capture-RNA: 7
  • Affinity Capture-Western: 56
  • Biochemical Activity: 6
  • Co-crystal Structure: 4
  • Co-fractionation: 3
  • Co-localization: 1
  • Co-purification: 7
  • PCA: 2
  • Protein-peptide: 1
  • Reconstituted Complex: 21
  • Two-hybrid: 7

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 7
  • Negative Genetic: 9
  • Phenotypic Enhancement: 17
  • Phenotypic Suppression: 5
  • Positive Genetic: 1
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 7
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 642
Molecular Weight (Da) 69,657
Isoelectric Point (pI) 4.82
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrI:141431 to 139503 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
This feature contains embedded feature(s): YAL004W
SGD ORF map
Genetic position: -1 cM
Last Update Coordinates: 2011-02-03 | Sequence: 2007-04-05
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1929 141431..139503 2011-02-03 2007-04-05
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 SGDIDS000000004
SUMMARY PARAGRAPH for SSA1

SSA1, SSA2, SSA3, and SSA4 encode chaperone proteins that comprise the S. cerevisiae SSA subfamily of cytosolic HSP70 proteins (10). 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. The main function of these proteins is to serve as molecular chaperones, binding newly-translated proteins to assist in proper folding and prevent aggregation/misfolding (reviewed in 11 and 12). In yeast, HSP70s are also involved in disassembling aggregates of misfolded proteins, translocating select proteins into the mitochondria and ER, degrading aberrant proteins, and regulating the expression of other heat shock proteins (13, 14, 15, 16, and reviewed in 17, 12, and 11). S. cerevisiae has at least 9 cytosolic forms of HSP70 (SSA1, SSA2, SSA3, SSA4, SSB1, SSB2, SSE1, SSE2, SSZ1), 2 HSP70s which are found in the endoplasmic reticulum (KAR2, LHS1), and 3 mitochondrial HSP70s (SSC1, SSQ1, ECM10).

The 4 genes of the SSA subfamily are closely related, with Ssa1p sharing 99%, 84%, and 85% amino acid identity with Ssa2p, Ssa3p, and Ssa4p, respectively (18). Although SSA1 basal expression is significant under normal growth conditions, transcription is also upregulated before diauxic shift or upon heat shock (19, 20). Increased expression after heat shock is mediated by the transcriptional activator Hsf1p, which recognizes and binds two heat shock elements (HSE) in the SSA1 promoter (21). Of the two HSEs, only one contributes to basal expression (22). Although the majority of Ssa protein is found in the cytosol, Ssa1p and Ssa2p can also be detected in the cell wall (3). Additionally, Ssa1p and Ssa2p have been implicated in DNA-damage as they have been identified as members of Rad9 DNA-checkpoint complexes (23, 24).

Most of the structural knowledge of the S. cerevisiae HSP70 proteins is based on experimental evidence from bacterial DnaK, mammalian HSP70, and Ssa1p (25 and reviewed in 11). All Hsp70s contain an N-terminal ATPase domain and a C-terminal peptide binding domain. ATPase activity of HSP70s is intrinsically weak but can be enhanced by interaction with DnaJ/HSP40 proteins (reviewed in 11). It has been shown for Ssa1p, and based on similarity is implicated for the remaining Ssa subfamily, that activity is stimulated by interaction with the DnaJ/HSP40 co-chaperones Ydj1p, Sis1p, Sti1p, and Cns1p (26, 27, 28, 29). Substrate binding is regulated by ATP turnover; in the presence of ATP, peptide exchange is rapid and the binding constant is low while when ADP is bound, peptide exchange is slower and the substrate affinity higher (reviewed in 11). The rate of Ssa protein ATP/ADP exchange is stimulated by the nucleotide exchange factors Fes1p and Snl1p (30, 31).

The effect of SSA1 expression has also been studied in yeast models of human prion disease such as Creutzfeldt-Jakob disease (OMIM). For the [PSI+] prion (an isoform of Sup35p), overexpression of any one of the Ssa proteins promotes prion formation and suppresses the ability of Hsp104p to cure prion propagation (32 and reviewed in 33). In contrast, overexpression of SSA1 is able to cure cells infected with the yeast prion [URE3] (an isoform of Ure2p) (34). In cells carrying the [PIN+] prion (an isoform of Rnq1p), ssa1ssa2 double null mutations result in the loss of polyglutamine aggregate expansion and toxicity, which are two hallmarks of Huntington disease (OMIM) (35).

Last updated: 2006-02-06 Contact SGD

References cited on this page View Complete Literature Guide for SSA1
1) Slater, M.  (1989) Personal Communication, Mortimer Map Edition 10
2) Ingolia TD, et al.  (1982) Saccharomyces cerevisiae contains a complex multigene family related to the major heat shock-inducible gene of Drosophila. Mol Cell Biol 2(11):1388-98
3) Lopez-Ribot JL and Chaffin WL  (1996) Members of the Hsp70 family of proteins in the cell wall of Saccharomyces cerevisiae. J Bacteriol 178(15):4724-6
4) Kim S, et al.  (1998) Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proc Natl Acad Sci U S A 95(22):12860-5
5) Shulga N, et al.  (1999) A nuclear export signal prevents Saccharomyces cerevisiae Hsp70 Ssb1p from stimulating nuclear localization signal-directed nuclear transport. J Biol Chem 274(23):16501-7
6) Ziegelhoffer T, et al.  (1995) The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated by both Ydj1p and peptide substrates. J Biol Chem 270(18):10412-9
7) Bush GL and Meyer DI  (1996) The refolding activity of the yeast heat shock proteins Ssa1 and Ssa2 defines their role in protein translocation. J Cell Biol 135(5):1229-37
8) Sharma D and Masison DC  (2011) Single methyl group determines prion propagation and protein degradation activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p. Proc Natl Acad Sci U S A 108(33):13665-70
9) Winkler J, et al.  (2012) Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation. J Cell Biol 198(3):387-404
10) Werner-Washburne M, et al.  (1987) Complex interactions among members of an essential subfamily of hsp70 genes in Saccharomyces cerevisiae. Mol Cell Biol 7(7):2568-77
11) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
12) Becker J and Craig EA  (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1-2):11-23
13) Glover JR and Lindquist S  (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94(1):73-82
14) Deshaies RJ, et al.  (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332(6167):800-5
15) Stone DE and Craig EA  (1990) Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae. Mol Cell Biol 10(4):1622-32
16) Nishikawa SI, et al.  (2001) Molecular chaperones in the yeast endoplasmic reticulum maintain the solubility of proteins for retrotranslocation and degradation. J Cell Biol 153(5):1061-70
17) Hartl FU  (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571-9
18) Boorstein WR, et al.  (1994) Molecular evolution of the HSP70 multigene family. J Mol Evol 38(1):1-17
19) Werner-Washburne M, et al.  (1989) Yeast Hsp70 RNA levels vary in response to the physiological status of the cell. J Bacteriol 171(5):2680-8
20) Slater MR and Craig EA  (1987) Transcriptional regulation of an hsp70 heat shock gene in the yeast Saccharomyces cerevisiae. Mol Cell Biol 7(5):1906-16
21) Halladay JT and Craig EA  (1995) A heat shock transcription factor with reduced activity suppresses a yeast HSP70 mutant. Mol Cell Biol 15(9):4890-7
22) Young MR and Craig EA  (1993) Saccharomyces cerevisiae HSP70 heat shock elements are functionally distinct. Mol Cell Biol 13(9):5637-46
23) Gilbert CS, et al.  (2003) The budding yeast Rad9 checkpoint complex: chaperone proteins are required for its function. EMBO Rep 4(10):953-8
24) van den Bosch M and Lowndes NF  (2004) Remodelling the Rad9 checkpoint complex: preparing Rad53 for action. Cell Cycle 3(2):119-22
25) Fung KL, et al.  (1996) Conformations of the nucleotide and polypeptide binding domains of a cytosolic Hsp70 molecular chaperone are coupled. J Biol Chem 271(35):21559-65
26) Becker J, et al.  (1996) Functional interaction of cytosolic hsp70 and a DnaJ-related protein, Ydj1p, in protein translocation in vivo. Mol Cell Biol 16(8):4378-86
27) Horton LE, et al.  (2001) The yeast hsp70 homologue Ssa is required for translation and interacts with Sis1 and Pab1 on translating ribosomes. J Biol Chem 276(17):14426-33
28) Wegele H, et al.  (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278(28):25970-6
29) Hainzl O, et al.  (2004) Cns1 is an activator of the Ssa1 ATPase activity. J Biol Chem 279(22):23267-73
30) Kabani M, et al.  (2002) Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol Cell Biol 22(13):4677-89
31) Sondermann H, et al.  (2002) Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 co-chaperone in Saccharomyces cerevisiae. J Biol Chem 277(36):33220-7
32) Allen KD, et al.  (2005) Hsp70 chaperones as modulators of prion life cycle: novel effects of Ssa and Ssb on the Saccharomyces cerevisiae prion [PSI+]. Genetics 169(3):1227-42
33) Jones GW and Tuite MF  (2005) Chaperoning prions: the cellular machinery for propagating an infectious protein? Bioessays 27(8):823-32
34) Schwimmer C and Masison DC  (2002) Antagonistic interactions between yeast [PSI(+)] and [URE3] prions and curing of [URE3] by Hsp70 protein chaperone Ssa1p but not by Ssa2p. Mol Cell Biol 22(11):3590-8
35) Gokhale KC, et al.  (2005) Modulation of prion-dependent polyglutamine aggregation and toxicity by chaperone proteins in the yeast model. J Biol Chem 280(24):22809-18