SSA2/YLL024C Summary Help

Standard Name SSA2
Systematic Name YLL024C
Alias YG102 1
Feature Type ORF, Verified
Description ATP-binding protein; involved in protein folding and vacuolar import of proteins; member of heat shock protein 70 (HSP70) family; associated with the chaperonin-containing T-complex; present in the cytoplasm, vacuolar membrane and cell wall; 98% identical with paralog Ssa1p, 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 (2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Stress-Seventy subfamily A
Chromosomal Location
ChrXII:97485 to 95566 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All SSA2 GO evidence and references
  View Computational GO annotations for SSA2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 19 genes
Classical genetics
Large-scale survey
475 total interaction(s) for 349 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 373
  • Affinity Capture-RNA: 6
  • Affinity Capture-Western: 25
  • Biochemical Activity: 3
  • Co-fractionation: 1
  • Co-purification: 2
  • PCA: 2
  • Protein-peptide: 4
  • Reconstituted Complex: 3
  • Two-hybrid: 7

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 21
  • Phenotypic Enhancement: 8
  • Positive Genetic: 2
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 5
  • Synthetic Rescue: 5

Expression Summary
Length (a.a.) 639
Molecular Weight (Da) 69,469
Isoelectric Point (pI) 4.77
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:97485 to 95566 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1920 97485..95566 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003947

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 8 and 9). 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 (10, 11, 12, 13, and reviewed in 14, 9, and 8). 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 Ssa2p sharing 99%, 84%, and 85% amino acid identity with Ssa1p, Ssa3p, and Ssa4p, respectively (15). SSA2 is the only member of the SSA subfamily whose transcription is not inducible by heat or stress; the SSA2 gene is constitutively expressed at high levels. Although the majority of Ssa protein is found in the cytosol, Ssa1p and Ssa2p can also be detected in the cell wall (2). An Ssa2p-GFP (green fluorescent protein) fusion protein was observed to relocate from the cytosol to the mitochondrial outer surface upon oxidative stress (16). Additionally, Ssa1p and Ssa2p have been implicated in DNA-damage as they have been identified as members of Rad9 DNA-checkpoint complexes (17, 18).

Most of the structural knowledge of the S. cerevisiae HSP70 proteins is based on experimental evidence from bacterial DnaK, mammalian HSP70, and Ssa1p (19 and reviewed in 8). 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 8). 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 (20, 21, 22, 23). 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 8). The rate of Ssa protein ATP/ADP exchange is stimulated by the nucleotide exchange factors Fes1p and Snl1p (24, 25).

The effect of SSA2 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 (26 and reviewed in 27). In contrast, a mutant allele of SSA2 has been shown to destabilize and prevent propagation of the yeast prion [URE3] (an isoform of Ure2p) (28, 29). 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) (30).

Last updated: 2006-02-06 Contact SGD

References cited on this page View Complete Literature Guide for SSA2
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) 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
3) Satyanarayana C, et al.  (2000) Cytosolic Hsp70s are involved in the transport of aminopeptidase 1 from the cytoplasm into the vacuole. FEBS Lett 470(3):232-8
4) Unno K, et al.  (1997) Role of Hsp70 subfamily, Ssa, in protein folding in yeast cells, seen in luciferase-transformed ssa mutants. Biol Pharm Bull 20(12):1240-4
5) Brown CR, et al.  (2000) The heat shock protein Ssa2p is required for import of fructose-1, 6-bisphosphatase into Vid vesicles. J Cell Biol 150(1):65-76
6) Anaul Kabir M, et al.  (2005) Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae. Yeast 22(3):219-39
7) 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
8) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
9) Becker J and Craig EA  (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1-2):11-23
10) Glover JR and Lindquist S  (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94(1):73-82
11) Deshaies RJ, et al.  (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332(6167):800-5
12) Stone DE and Craig EA  (1990) Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae. Mol Cell Biol 10(4):1622-32
13) 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
14) Hartl FU  (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571-9
15) Boorstein WR, et al.  (1994) Molecular evolution of the HSP70 multigene family. J Mol Evol 38(1):1-17
16) Rinnerthaler M, et al.  (2006) MMI1 (YKL056c, TMA19), the yeast orthologue of the translationally controlled tumor protein (TCTP) has apoptotic functions and interacts with both microtubules and mitochondria. Biochim Biophys Acta 1757(5-6):631-8
17) Gilbert CS, et al.  (2003) The budding yeast Rad9 checkpoint complex: chaperone proteins are required for its function. EMBO Rep 4(10):953-8
18) van den Bosch M and Lowndes NF  (2004) Remodelling the Rad9 checkpoint complex: preparing Rad53 for action. Cell Cycle 3(2):119-22
19) 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
20) 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
21) 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
22) Wegele H, et al.  (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278(28):25970-6
23) Hainzl O, et al.  (2004) Cns1 is an activator of the Ssa1 ATPase activity. J Biol Chem 279(22):23267-73
24) Kabani M, et al.  (2002) Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol Cell Biol 22(13):4677-89
25) 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
26) 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
27) Jones GW and Tuite MF  (2005) Chaperoning prions: the cellular machinery for propagating an infectious protein? Bioessays 27(8):823-32
28) 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
29) Tibor Roberts B, et al.  (2004) [URE3] prion propagation is abolished by a mutation of the primary cytosolic Hsp70 of budding yeast. Yeast 21(2):107-17
30) 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