SSA4/YER103W Summary Help

Standard Name SSA4
Systematic Name YER103W
Alias YG107 1
Feature Type ORF, Verified
Description Heat shock protein that is highly induced upon stress; plays a role in SRP-dependent cotranslational protein-membrane targeting and translocation; member of the HSP70 family; cytoplasmic protein that concentrates in nuclei upon starvation; SSA4 has a paralog, SSA3, that arose from the whole genome duplication (2, 3, 4, 5 and see Summary Paragraph)
Name Description Stress-Seventy subfamily A
Chromosomal Location
ChrV:364589 to 366517 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All SSA4 GO evidence and references
  View Computational GO annotations for SSA4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 19 genes
Resources
Classical genetics
null
overexpression
Large-scale survey
null
Resources
66 total interaction(s) for 41 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 40
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 3
  • Co-localization: 2
  • Reconstituted Complex: 2
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Rescue: 1
  • Phenotypic Enhancement: 5
  • Positive Genetic: 1
  • Synthetic Lethality: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 642
Molecular Weight (Da) 69,650
Isoelectric Point (pI) 4.86
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrV:364589 to 366517 | 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..1929 364589..366517 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 SGDIDS000000905
SUMMARY PARAGRAPH for SSA4

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 6 and 7). 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 (8, 9, 10, 11, and reviewed in 12, 7, and 6). 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 Ssa4p sharing 85% amino acid identity with Ssa1p and Ssa2p and 90% identity with Ssa3p (13). SSA4 null mutants are viable and have no phenotype that is distinguishable from wild-type yeast (1). SSA4 expression is not detectable under normal growth conditions, but is upregulated upon heat shock, cold and ethanol stress, and during diauxic shift (3, 14, 15, 16). Increased expression after heat shock is mediated by the transcriptional activator Hsf1p, which recognizes and binds a heat shock element in the SSA4 promoter (17, 3). In ssa1ssa2 double null mutant cells, SSA4 is highly expressed, even under non-inducing conditions, and is able to sustain growth (1). In starved or ethanol-stressed cells, Ssa4p accumulates in the nucleus, a process which is mediated by a hydrophobic stretch in the N-terminal domain of Ssa4p and the beta-importin Nmd5p (4, 15).

Most of the structural knowledge of the S. cerevisiae HSP70 proteins is based on experimental evidence from bacterial DnaK, mammalian HSP70, and Ssa1p (18 and reviewed in 6). 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 6). 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, 19, 20, 21). 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 6). The rate of Ssa protein ATP/ADP exchange is stimulated by the nucleotide exchange factors Fes1p and Snl1p (22, 23).

The effect of SSA4 expression has also been studied in yeast models of human disease, such as the prion disease Creutzfeldt-Jakob disease (OMIM), Huntington disease (OMIM), and Parkinson disease (OMIM). In cells carrying the yeast prion [PSI+] (isoform of Sup35p), excess Ssa protein promotes prion formation and propagation and also inhibits the curing affect of Hsp104p (24). In contrast, overexpression of SSA4 counteracts polyglutamine aggregation and toxicity, which are two hallmarks of Huntington disease, that are observed in yeast cells propagating the [PIN+] prion form of Rnq1p (25). SSA4 has also been implicated in protecting S. cerevisiae cells that express human alpha-synuclein, the protein that forms amyloid fibers in Parkinson disease, from apoptosis (26).

Last updated: 2006-02-06 Contact SGD

References cited on this page View Complete Literature Guide for SSA4
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) Boorstein WR and Craig EA  (1990) Structure and regulation of the SSA4 HSP70 gene of Saccharomyces cerevisiae. J Biol Chem 265(31):18912-21
4) Chughtai ZS, et al.  (2001) Starvation promotes nuclear accumulation of the hsp70 Ssa4p in yeast cells. J Biol Chem 276(23):20261-6
5) 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
6) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
7) Becker J and Craig EA  (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1-2):11-23
8) Glover JR and Lindquist S  (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94(1):73-82
9) Deshaies RJ, et al.  (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332(6167):800-5
10) Stone DE and Craig EA  (1990) Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae. Mol Cell Biol 10(4):1622-32
11) 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
12) Hartl FU  (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571-9
13) Boorstein WR, et al.  (1994) Molecular evolution of the HSP70 multigene family. J Mol Evol 38(1):1-17
14) Kandror O, et al.  (2004) Yeast adapt to near-freezing temperatures by STRE/Msn2,4-dependent induction of trehalose synthesis and certain molecular chaperones. Mol Cell 13(6):771-81
15) Quan X, et al.  (2004) Regulated nuclear accumulation of the yeast hsp70 Ssa4p in ethanol-stressed cells is mediated by the N-terminal domain, requires the nuclear carrier Nmd5p and protein kinase C. FASEB J 18(7):899-901
16) 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
17) 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
18) 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
19) 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
20) Wegele H, et al.  (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278(28):25970-6
21) Hainzl O, et al.  (2004) Cns1 is an activator of the Ssa1 ATPase activity. J Biol Chem 279(22):23267-73
22) Kabani M, et al.  (2002) Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol Cell Biol 22(13):4677-89
23) 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
24) 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
25) 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
26) 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