SSC1/YJR045C Summary Help

Standard Name SSC1 1
Systematic Name YJR045C
Alias ENS1 2
Feature Type ORF, Verified
Description Hsp70 family ATPase; constituent of the import motor component of the Translocase of the Inner Mitochondrial membrane (TIM23 complex); involved in protein translocation and folding; subunit of SceI endonuclease; SSC1 has a paralog, ECM10, that arose from the whole genome duplication (2, 3, 4, 5, 6 and see Summary Paragraph)
Also known as: mtHSP70
Name Description Stress-Seventy subfamily C
Chromosomal Location
ChrX:521602 to 519638 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All SSC1 GO evidence and references
  View Computational GO annotations for SSC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 18 genes
Resources
Classical genetics
conditional
null
reduction of function
Large-scale survey
null
overexpression
reduction of function
Resources
194 total interaction(s) for 107 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 50
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 49
  • Biochemical Activity: 4
  • Co-fractionation: 1
  • Co-purification: 5
  • FRET: 1
  • PCA: 1
  • Reconstituted Complex: 12
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 7
  • Negative Genetic: 43
  • Phenotypic Suppression: 1
  • Positive Genetic: 3
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 654
Molecular Weight (Da) 70,627
Isoelectric Point (pI) 5.34
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:521602 to 519638 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
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..1965 521602..519638 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 SGDIDS000003806
SUMMARY PARAGRAPH for SSC1

About mitochondrial import

While the mitochondrial genome encodes a handful of proteins, most of the hundreds of proteins that reside in the mitochondrion are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria via a series of complex molecular machines (see 7, 8 for review). Many of the proteins imported into mitochondria are involved in respiration, which is not an essential process: S. cerevisiae is able to carry out either fermentative growth on carbon sources such as glucose, or respiratory growth on nonfermentable carbon sources such as glycerol and ethanol. However, since maintenance of the mitochondrial compartment is essential to life, mutations that completely disrupt mitochondrial import are lethal.

About the TIM23 complex

The Translocase of the Inner Mitochondrial membrane (TIM23 complex) receives proteins from the Translocase of the Outer Mitochondrial membrane (TOM complex) and either directs them into the mitochondrial matrix or facilitates their integration into the mitochondrial inner membrane (reviewed in 9, 8, 10). The membrane-embedded core of the complex is composed of three essential proteins: Tim23p, Tim17p, and Tim50p. Tim23p and Tim17p, which share sequence similarity, comprise the twin-pore structure through which precursor proteins translocate. Tim23p alone has the ability to form a voltage-sensitive channel (11), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (12). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (13). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (14, 15). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (13, 16, 17).

Proteins destined for the mitochondrial matrix require the action of a sub-complex of the TIM23 complex, known as the import motor or presequence translocase-associated motor (PAM) complex. Its catalytic component is Ssc1p, a member of the heat shock 70 protein family commonly referred to as mtHsp70, which undergoes cycles of binding and release of the precursor, hydrolyzing ATP and changing conformation in the process. The nucleotide release factor Mge1p promotes this cycle by facilitating the dissociation of ADP from Ssc1p (18, 19). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (20, 17); Pam18p (Tim14p), a J-protein cochaperone that stimulates the ATPase activity of Ssc1p; and Pam16p (Tim16p), a J-like protein that binds to Pam18p and regulates its activity (21). Pam17p mediates the association between Pam16p and Pam18p (22). Once imported proteins reach the mitochondrial matrix, their correct folding is facilitated by a soluble complex consisting of Ssc1p and its cochaperones Mdj1p and Mge1p (23).

A subset of proteins destined for insertion into the mitochondrial inner membrane is translocated via the TIM23 complex but then inserted laterally into the inner membrane rather than entering the mitochondrial matrix. This mechanism is currently not understood in detail. The TIM23 complex adopts different conformations during the two kinds of import, but it is unclear whether this inner membrane import is accomplished by the core complex alone (Tim23p, Tim17p, and Tim50p), or by the entire TIM23 complex including the import motor subunits (9, 16).

About SSC1

SSC1 encodes an essential chaperone that is the key component of the import motor sub-complex that mediates the transit of precursor proteins through the TIM23 complex (1, 24, 25). Ssc1p uses energy derived from ATP hydrolysis to facilitate protein translocation, with the help of its cochaperones Pam18p and Mge1p (18, 19). It also forms a soluble complex in the mitochondrial matrix, consisting of Ssc1p with its cochaperones Mge1p and Mdj1p, that re-folds newly imported proteins (26). Additionally, Ssc1p binds to Ens2p, a mitochondrially-encoded protein whose gene is present in some S. cerevisiae strains but not others, to act as a regulatory subunit of the site-specific endonuclease Endo.SceI (2). Like all other Hsp70 proteins, Ssc1p contains an N-terminal ATPase domain; in the absence of nucleotide binding Ssc1p is prone to form insoluble self-aggregates, an event which can be prevented by the chaperone protein Zim17p (27).

SSC1, SSQ1, and ECM10 encode chaperone proteins of the HSP70 family that localize to the mitochondria (28 and reviewed in 29). In addition to these three mitochondrial HSP70s, S. cerevisiae cells also synthesize nine cytosolic HSPs (encoded by SSA1, SSA2, SSA3, SSA4, SSB1, SSB2, SSE1, SSE2, SSZ1) and two that are found in the ER (KAR2, LHS1). 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 unfolded peptides to assist in proper folding and prevent aggregation/misfolding (reviewed in 30 and 31). HSP70s are also involved in disassembling aggregates of misfolded proteins, translocating select proteins into the mitochondria and ER, and degrading aberrant proteins (reviewed in 32, 31, and 30).

Last updated: 2006-02-09 Contact SGD

References cited on this page View Complete Literature Guide for SSC1
1) Craig EA, et al.  (1987) SSC1, a member of the 70-kDa heat shock protein multigene family of Saccharomyces cerevisiae, is essential for growth. Proc Natl Acad Sci U S A 84(12):4156-60
2) Morishima N, et al.  (1990) A subunit of yeast site-specific endonuclease SceI is a mitochondrial version of the 70-kDa heat shock protein. J Biol Chem 265(25):15189-97
3) Lopez-Buesa P, et al.  (1998) The biochemical properties of the ATPase activity of a 70-kDa heat shock protein (Hsp70) are governed by the C-terminal domains. Proc Natl Acad Sci U S A 95(26):15253-8
4) Truscott KN, et al.  (2003) A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol 163(4):707-13
5) Liu Q, et al.  (2001) Mitochondrial Hsp70 Ssc1: role in protein folding. J Biol Chem 276(9):6112-8
6) 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
7) Neupert W and Herrmann JM  (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723-49
8) Mokranjac D and Neupert W  (2009) Thirty years of protein translocation into mitochondria: unexpectedly complex and still puzzling. Biochim Biophys Acta 1793(1):33-41
9) Wagner K, et al.  (2009) Protein transport machineries for precursor translocation across the inner mitochondrial membrane. Biochim Biophys Acta 1793(1):52-9
10) Bolender N, et al.  (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9(1):42-9
11) Truscott KN, et al.  (2001) A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23. Nat Struct Biol 8(12):1074-82
12) Martinez-Caballero S, et al.  (2007) Tim17p regulates the twin pore structure and voltage gating of the mitochondrial protein import complex TIM23. J Biol Chem 282(6):3584-93
13) Chacinska A, et al.  (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817-29
14) Mokranjac D, et al.  (2009) Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria. Mol Biol Cell 20(5):1400-7
15) Gevorkyan-Airapetov L, et al.  (2009) Interaction of Tim23 with Tim50 Is Essential for Protein Translocation by the Mitochondrial TIM23 Complex. J Biol Chem 284(8):4865-72
16) Popov-Celeketic D, et al.  (2008) Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria. EMBO J 27(10):1469-80
17) Hutu DP, et al.  (2008) Mitochondrial protein import motor: differential role of tim44 in the recruitment of pam17 and j-complex to the presequence translocase. Mol Biol Cell 19(6):2642-9
18) Schneider HC, et al.  (1996) The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J 15(21):5796-803
19) Liu Q, et al.  (2003) Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300(5616):139-41
20) D'Silva P, et al.  (2004) Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nat Struct Mol Biol 11(11):1084-91
21) Mokranjac D, et al.  (2006) Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J 25(19):4675-85
22) Van Der Laan M, et al.  (2005) Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol 25(17):7449-58
23) Kubo Y, et al.  (1999) Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system. J Mol Biol 286(2):447-64
24) Kang PJ, et al.  (1990) Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature 348(6297):137-43
25) Voos W, et al.  (1993) Presequence and mature part of preproteins strongly influence the dependence of mitochondrial protein import on heat shock protein 70 in the matrix. J Cell Biol 123(1):119-26
26) Horst M, et al.  (1997) Sequential action of two hsp70 complexes during protein import into mitochondria. EMBO J 16(8):1842-9
27) Sichting M, et al.  (2005) Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1. EMBO J 24(5):1046-56
28) Baumann F, et al.  (2000) Ecm10, a novel hsp70 homolog in the mitochondrial matrix of the yeast Saccharomyces cerevisiae. FEBS Lett 487(2):307-12
29) Voos W and Rottgers K  (2002) Molecular chaperones as essential mediators of mitochondrial biogenesis. Biochim Biophys Acta 1592(1):51-62
30) Bukau B and Horwich AL  (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351-66
31) Becker J and Craig EA  (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1-2):11-23
32) Hartl FU  (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571-9