|Gene:||prc||Accession Numbers: EG10760 (EcoCyc), b1830, ECK1829|
Synonyms: tsp, carboxy-terminal protease for penicillin-binding protein 3, c-terminal processing peptidase, protease re
Tail-specific protease (Tsp) is an ATP-independent periplasmic protease responsible for processing and degradation of a number of proteins [Park88a]. Specific substrates for Tsp include penicillin-binding protein 3 and NlpI, both of which undergo carboxy-terminal cleavage to become functional [Hara91, Hara89, Nagasawa89, Tadokoro04]. Tsp also binds to and degrades proteins that have been tagged with the quality control peptide sequence coded for by ssrA, indicating a possible role in removing improperly translated proteins [Spiers02, Keiler96]. Tsp proteolyzes oxidized glutamine synthetase, Arc repressor and a mutant of the N-terminal domain of lambda repressor in vitro, but loss of Tsp has no effect on that same lambda repressor mutant in vivo [Lee88, Roseman87, Keiler95, Silber92, Silber94].
Tsp catalyzes the hydrolysis of a peptide bond in the carboxy-terminal region of its substrate protein. The carboxy-terminal residue is an important determinant of cleavage rate, with the highest rates afforded by alanine, cysteine, serine, threonine and valine. Nonpolar residues at the second and third position from the carboxy-terminus also allow more rapid proteolysis [Keiler96a]. Actual hydrolysis occurs most often after alanine, as well as following serine, valine, isoleucine and leucine [Silber92, Keiler95, Nagasawa89].
Tsp contains a PDZ domain that binds to nonpolar residues, which may help set its substrate specificity for proteins with nonpolar carboxy-terminal tags [Beebe00]. The PDZ domain is required for binding to the SsrA degradation tag [Spiers02].
Tsp's activity depends on a serine430-lysine455 catalytic dyad [Keiler95a].
Tsp may have some redundancy with HhoA, HhoB and DksA, as they were able to suppress the deleterious effects of losing Prc [Bass96].
prc is one of a network of 93 genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12]. prc insertion mutants were identified in a genetic screen for genes that are important for survival of exposure to ionizing radiation (IR). A prc deletion mutant has a moderate decrease in IR survival [Byrne14].
Locations: periplasmic space, inner membrane
|Map Position: [1,910,792 <- 1,912,840] (41.18 centisomes)||Length: 2049 bp / 682 aa|
Molecular Weight of Polypeptide: 76.663 kD (from nucleotide sequence)
pI: 6.8 [Park88a]
Unification Links: ASAP:ABE-0006090 , CGSC:32334 , DIP:DIP-10557N , EchoBASE:EB0753 , EcoGene:EG10760 , EcoliWiki:b1830 , EcoO157Cyc:PRC-MONOMER , Mint:MINT-1283244 , ModBase:P23865 , OU-Microarray:b1830 , PortEco:prc , PR:PRO_000023587 , Pride:P23865 , Protein Model Portal:P23865 , RefSeq:NP_416344 , RegulonDB:EG10760 , SMR:P23865 , String:511145.b1830 , UniProt:P23865
Relationship Links: InterPro:IN-FAMILY:IPR001478 , InterPro:IN-FAMILY:IPR004447 , InterPro:IN-FAMILY:IPR005151 , InterPro:IN-FAMILY:IPR020992 , Pfam:IN-FAMILY:PF00595 , Pfam:IN-FAMILY:PF03572 , Pfam:IN-FAMILY:PF11818 , Prosite:IN-FAMILY:PS50106 , Smart:IN-FAMILY:SM00228 , Smart:IN-FAMILY:SM00245
In Paralogous Gene Group: 508 (2 members)
|Biological Process:||GO:0006508 - proteolysis
[UniProtGOA11, GOA01, Keiler95]
GO:0030163 - protein catabolic process [Keiler95]
GO:0046677 - response to antibiotic [Seoane92]
|Molecular Function:||GO:0004175 - endopeptidase activity
GO:0008233 - peptidase activity [UniProtGOA11]
GO:0008236 - serine-type peptidase activity [UniProtGOA11, GOA01]
GO:0016787 - hydrolase activity [UniProtGOA11]
|Cellular Component:||GO:0030288 - outer membrane-bounded periplasmic space
GO:0005886 - plasma membrane [UniProtGOA11a, UniProtGOA11]
GO:0016020 - membrane [UniProtGOA11]
|MultiFun Terms:||cell processes → protection → drug resistance/sensitivity|
|cell structure → murein|
|information transfer → protein related → turnover, degradation|
|metabolism → biosynthesis of macromolecules (cellular constituents) → murein (peptidoglycan)|
|metabolism → degradation of macromolecules → proteins/peptides/glycopeptides|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB enriched||Yes||37||Aerobic||6.95||Yes [Gerdes03, Comment 1]|
Enzymatic reaction of: tail-specific protease
EC Number: 184.108.40.206
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is physiologically favored in the direction shown.
|Signal-Sequence||1 -> 22|
|Chain||23 -> 682|
|Conserved-Region||238 -> 322|
10/20/97 Gene b1830 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10760; confirmed by SwissProt match.
Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554
Azizan94: Azizan A, Black PN (1994). "Use of transposon TnphoA to identify genes for cell envelope proteins of Escherichia coli required for long-chain fatty acid transport: the periplasmic protein Tsp potentiates long-chain fatty acid transport." J Bacteriol 176(21);6653-62. PMID: 7961418
Bass96: Bass S, Gu Q, Christen A (1996). "Multicopy suppressors of prc mutant Escherichia coli include two HtrA (DegP) protease homologs (HhoAB), DksA, and a truncated RlpA." J Bacteriol 178(4);1154-61. PMID: 8576052
Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938
Hara89: Hara H, Nishimura Y, Kato J, Suzuki H, Nagasawa H, Suzuki A, Hirota Y (1989). "Genetic analyses of processing involving C-terminal cleavage in penicillin-binding protein 3 of Escherichia coli." J Bacteriol 171(11);5882-9. PMID: 2681145
Hara91: Hara H, Yamamoto Y, Higashitani A, Suzuki H, Nishimura Y (1991). "Cloning, mapping, and characterization of the Escherichia coli prc gene, which is involved in C-terminal processing of penicillin-binding protein 3." J Bacteriol 173(15);4799-813. PMID: 1856173
Keiler95: Keiler KC, Silber KR, Downard KM, Papayannopoulos IA, Biemann K, Sauer RT (1995). "C-terminal specific protein degradation: activity and substrate specificity of the Tsp protease." Protein Sci 4(8);1507-15. PMID: 8520476
Nagasawa89: Nagasawa H, Sakagami Y, Suzuki A, Suzuki H, Hara H, Hirota Y (1989). "Determination of the cleavage site involved in C-terminal processing of penicillin-binding protein 3 of Escherichia coli." J Bacteriol 171(11);5890-3. PMID: 2681146
Silber94: Silber KR, Sauer RT (1994). "Deletion of the prc (tsp) gene provides evidence for additional tail-specific proteolytic activity in Escherichia coli K-12." Mol Gen Genet 242(2);237-40. PMID: 8159175
Spiers02: Spiers A, Lamb HK, Cocklin S, Wheeler KA, Budworth J, Dodds AL, Pallen MJ, Maskell DJ, Charles IG, Hawkins AR (2002). "PDZ domains facilitate binding of high temperature requirement protease A (HtrA) and tail-specific protease (Tsp) to heterologous substrates through recognition of the small stable RNA A (ssrA)-encoded peptide." J Biol Chem 277(42);39443-9. PMID: 12177052
Tadokoro04: Tadokoro A, Hayashi H, Kishimoto T, Makino Y, Fujisaki S, Nishimura Y (2004). "Interaction of the Escherichia coli lipoprotein NlpI with periplasmic Prc (Tsp) protease." J Biochem (Tokyo) 135(2);185-91. PMID: 15047720
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