Escherichia coli K-12 substr. MG1655 Polypeptide: specificity factor for ClpA-ClpP chaperone-protease complex

Gene: clpS Accession Numbers: G6463 (EcoCyc), b0881, ECK0872

Synonyms: yljA

Regulation Summary Diagram: ?

Regulation summary diagram for clpS

ClpS is a specificity adapter for the ClpAP protease complex, targeting it to aggregated proteins, N-end rule substrates, and others.

ClpS binds to the ClpA amino-terminus and affects the specificity of protein degradation by the ClpAP chaperone-protease complex, possibly by interfering with interactions between substrate and ClpA [Dougan02a]. ClpS stimulates ClpAP recognition and degradation of aggregated protein substrates while it inhibits degradation of non-aggregated substrates, including ClpA [Dougan02a]. ClpS also links ClpAP to the N-end rule degradation pathway, binding to the amino-terminal destabilizing residues in N-end substrates and targeting those subtrates for degradation by ClpAP [Erbse06].

A mutant protein lacking the flexible 17 amino-terminal residues shows a defect in ClpA inhibition but does not show a defect in interaction with ClpA [Guo02]. Binding of ClpA and ClpS requires ClpS residues E79 and K84, as does proteolytic activity by the ClpAPS complex [Zeth02].

ClpS has structural similarity to the ribosomal protein L7/L12 [Guo02, Lupas03]. ClpS has similarity to the eukaryotic N-recognin E3 ubiquitin ligase and to proteins of plant chloroplast, actinobacteria, and cyanobacteria [Lupas03].

Crystal structures of ClpS bound the the amino-terminal region of ClpA are presented at 2.3 [Guo02], 2.5 [Zeth02], and 3.3 [Guo02] Å resolution, and crystallization has been described [Zeth02a].

ClpS shows OxyR-dependent induction of expression by hydrogen peroxide [Zheng01a].

clpS shows differential codon adaptation, resulting in differential translation efficiency signatures, in thermophilic microbes. It was therefore predicted to play a role in the heat shock response. A clpS deletion mutant was shown to be more sensitive than wild-type specifically to heat shock, but not other stresses [Krisko14].

Locations: cytosol

Map Position: [922,136 -> 922,456] (19.88 centisomes, 72°)
Length: 321 bp / 106 aa

Molecular Weight of Polypeptide: 12.179 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0002998 , DIP:DIP-35408N , EchoBASE:EB3992 , EcoGene:EG14241 , EcoliWiki:b0881 , Mint:MINT-365090 , ModBase:P0A8Q6 , OU-Microarray:b0881 , PortEco:clpS , PR:PRO_000022299 , Pride:P0A8Q6 , Protein Model Portal:P0A8Q6 , RefSeq:NP_415402 , RegulonDB:G6463 , SMR:P0A8Q6 , String:511145.b0881 , UniProt:P0A8Q6

Relationship Links: InterPro:IN-FAMILY:IPR003769 , InterPro:IN-FAMILY:IPR014719 , InterPro:IN-FAMILY:IPR022935 , PDB:Structure:1LZW , PDB:Structure:1MBU , PDB:Structure:1MBV , PDB:Structure:1MBX , PDB:Structure:1MG9 , PDB:Structure:1R6O , PDB:Structure:1R6Q , PDB:Structure:2W9R , PDB:Structure:2WA8 , PDB:Structure:2WA9 , PDB:Structure:3O1F , PDB:Structure:3O2B , PDB:Structure:3O2H , PDB:Structure:3O2O , Pfam:IN-FAMILY:PF02617

GO Terms:

Biological Process: GO:0009408 - response to heat Inferred from experiment [Krisko14]
GO:0006508 - proteolysis Inferred by computational analysis [GOA06]
GO:0030163 - protein catabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Hauser14, Ninnis09, Schuenemann09, Schmidt09, Butland05, Xia04, Zeth02, Guo02]
GO:0051087 - chaperone binding Inferred from experiment [Dougan02a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer protein related turnover, degradation
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Essentiality data for clpS knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01 ].
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dougan02a: Dougan DA, Reid BG, Horwich AL, Bukau B (2002). "ClpS, a substrate modulator of the ClpAP machine." Mol Cell 2002;9(3);673-83. PMID: 11931773

Erbse06: Erbse A, Schmidt R, Bornemann T, Schneider-Mergener J, Mogk A, Zahn R, Dougan DA, Bukau B (2006). "ClpS is an essential component of the N-end rule pathway in Escherichia coli." Nature 439(7077);753-6. PMID: 16467841

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Guo02: Guo F, Esser L, Singh SK, Maurizi MR, Xia D (2002). "Crystal structure of the heterodimeric complex of the adaptor, ClpS, with the N-domain of the AAA+ chaperone, ClpA." J Biol Chem 277(48);46753-62. PMID: 12235156

Hauser14: Hauser R, Ceol A, Rajagopala SV, Mosca R, Siszler G, Wermke N, Sikorski P, Schwarz F, Schick M, Wuchty S, Aloy P, Uetz P (2014). "A Second-generation Protein-Protein Interaction Network of Helicobacter pylori." Mol Cell Proteomics 13(5);1318-29. PMID: 24627523

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Krisko14: Krisko A, Copi T, Gabaldon T, Lehner B, Supek F (2014). "Inferring gene function from evolutionary change in signatures of translation efficiency." Genome Biol 15(3);R44. PMID: 24580753

Lupas03: Lupas AN, Koretke KK (2003). "Bioinformatic analysis of ClpS, a protein module involved in prokaryotic and eukaryotic protein degradation." J Struct Biol 2003;141(1);77-83. PMID: 12576022

Ninnis09: Ninnis RL, Spall SK, Talbo GH, Truscott KN, Dougan DA (2009). "Modification of PATase by L/F-transferase generates a ClpS-dependent N-end rule substrate in Escherichia coli." EMBO J 28(12);1732-44. PMID: 19440203

Schmidt09: Schmidt R, Zahn R, Bukau B, Mogk A (2009). "ClpS is the recognition component for Escherichia coli substrates of the N-end rule degradation pathway." Mol Microbiol 72(2);506-17. PMID: 19317833

Schuenemann09: Schuenemann VJ, Kralik SM, Albrecht R, Spall SK, Truscott KN, Dougan DA, Zeth K (2009). "Structural basis of N-end rule substrate recognition in Escherichia coli by the ClpAP adaptor protein ClpS." EMBO Rep 10(5);508-14. PMID: 19373253

Serres01: Serres MH, Gopal S, Nahum LA, Liang P, Gaasterland T, Riley M (2001). "A functional update of the Escherichia coli K-12 genome." Genome Biol 2(9);RESEARCH0035. PMID: 11574054

Xia04: Xia D, Esser L, Singh SK, Guo F, Maurizi MR (2004). "Crystallographic investigation of peptide binding sites in the N-domain of the ClpA chaperone." J Struct Biol 146(1-2);166-79. PMID: 15037248

Zeth02: Zeth K, Ravelli RB, Paal K, Cusack S, Bukau B, Dougan DA (2002). "Structural analysis of the adaptor protein ClpS in complex with the N-terminal domain of ClpA." Nat Struct Biol 2002;9(12);906-11. PMID: 12426582

Zeth02a: Zeth K, Dougan DA, Cusack S, Bukau B, Ravelli RB (2002). "Crystallization and preliminary X-ray analysis of the Escherichia coli adaptor protein ClpS, free and in complex with the N-terminal domain of ClpA." Acta Crystallogr D Biol Crystallogr 2002;58(Pt 7);1207-10. PMID: 12077445

Zheng01a: Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G (2001). "DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide." J Bacteriol 183(15);4562-70. PMID: 11443091

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Fri Oct 9, 2015, biocyc14.