SSA3/YBL075C Summary Help

Standard Name SSA3
Systematic Name YBL075C
Alias YG106 1
Feature Type ORF, Verified
Description ATPase involved in protein folding and the response to stress; plays a role in SRP-dependent cotranslational protein-membrane targeting and translocation; member of the heat shock protein 70 (HSP70) family; localized to the cytoplasm; SSA3 has a paralog, SSA4, that arose from the whole genome duplication (1, 2, 3, 4 and see Summary Paragraph)
Name Description Stress-Seventy subfamily A
Chromosomal Location
ChrII:86448 to 84499 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All SSA3 GO evidence and references
  View Computational GO annotations for SSA3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 8 genes
Classical genetics
Large-scale survey
112 total interaction(s) for 90 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 43
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 13
  • Biochemical Activity: 1
  • Co-crystal Structure: 1
  • Co-purification: 1
  • PCA: 1
  • Two-hybrid: 7

Genetic Interactions
  • Dosage Rescue: 5
  • Negative Genetic: 23
  • Phenotypic Enhancement: 6
  • Positive Genetic: 5
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 649
Molecular Weight (Da) 70,546
Isoelectric Point (pI) 4.89
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrII:86448 to 84499 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1950 86448..84499 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000171

SSA1, SSA2, SSA3, and SSA4 encode chaperone proteins that comprise the S. cerevisiae SSA subfamily of cytosolic HSP70 proteins (1). 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 5 and 6). 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 (7, 8, 9, 10, and reviewed in 11, 6, and 5). 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 Ssa3p sharing 84% amino acid identity with Ssa1p and Ssa2p and 90% identity with Ssa4p (12). SSA3 expression is not detectable under normal growth conditions but is induced after the diauxic shift or upon heat shock (13, 1). Increased expression after heat shock is mediated by the transcriptional activator Hsf1p, which recognizes and binds to a heat shock element in the SSA3 promoter (14, 15). An SSA3 null mutant is viable and has no detectable phenotype. In an ssa1ssa2ssa4 triple null mutant, endogenous levels of Ssa3p are not enough to sustain viability, but expression of the SSA3 gene from the endogenous SSA2 promoter is able to rescue the cells (1).

Most of the structural knowledge of the S. cerevisiae HSP70 proteins is based on experimental evidence from bacterial DnaK, mammalian HSP70, and Ssa1p (16 and reviewed in 5). 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 5). 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 (2, 17, 18, 19). 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 5). The rate of Ssa protein ATP/ADP exchange is stimulated by the nucleotide exchange factors Fes1p and Snl1p (20, 21).

The effect of SSA3 expression has also been studied in yeast models of human disease, such as the prion disease Creutzfeldt-Jakob disease (OMIM) and Parkinson disease (OMIM). Overexpression of any of the SSA gene products promotes the formation of the [PSI+] prion (an isoform of Sup35p) and suppresses the ability of Hsp104p to cure prion propagation (22 and reviewed in 23). However, overexpression of Ssa3p has been shown to protect S. cerevisiae cells that express the human alpha-synuclein, the protein that forms amyloid fibers in Parkinson disease, from apoptosis (24).

Last updated: 2006-02-06 Contact SGD

References cited on this page View Complete Literature Guide for SSA3
1) 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
2) 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
3) Hartl FU and Hayer-Hartl M  (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295(5561):1852-8
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) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
6) Becker J and Craig EA  (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1-2):11-23
7) Glover JR and Lindquist S  (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94(1):73-82
8) Deshaies RJ, et al.  (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332(6167):800-5
9) Stone DE and Craig EA  (1990) Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae. Mol Cell Biol 10(4):1622-32
10) 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
11) Hartl FU  (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571-9
12) Boorstein WR, et al.  (1994) Molecular evolution of the HSP70 multigene family. J Mol Evol 38(1):1-17
13) 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
14) Boorstein WR and Craig EA  (1990) Transcriptional regulation of SSA3, an HSP70 gene from Saccharomyces cerevisiae. Mol Cell Biol 10(6):3262-7
15) Nelson RJ, et al.  (1992) Isolation and characterization of extragenic suppressors of mutations in the SSA hsp70 genes of Saccharomyces cerevisiae. Genetics 131(2):277-85
16) 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
17) 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
18) Wegele H, et al.  (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278(28):25970-6
19) Hainzl O, et al.  (2004) Cns1 is an activator of the Ssa1 ATPase activity. J Biol Chem 279(22):23267-73
20) Kabani M, et al.  (2002) Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol Cell Biol 22(13):4677-89
21) 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
22) 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
23) Jones GW and Tuite MF  (2005) Chaperoning prions: the cellular machinery for propagating an infectious protein? Bioessays 27(8):823-32
24) Flower TR, et al.  (2005) Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson's disease. J Mol Biol 351(5):1081-100