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Escherichia coli K-12 substr. MG1655 Enzyme: tail-specific protease



Gene: prc Accession Numbers: EG10760 (EcoCyc), b1830, ECK1829

Synonyms: tsp, carboxy-terminal protease for penicillin-binding protein 3, c-terminal processing peptidase, protease re

Regulation Summary Diagram: ?

Summary:
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 is required for efficient transport of long-chain fatty acids and for resistance to a number of antibiotics [Azizan94, Seoane92].

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)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006508 - proteolysis Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Keiler95]
GO:0030163 - protein catabolic process Inferred from experiment [Keiler95]
GO:0046677 - response to antibiotic Inferred from experiment [Seoane92]
Molecular Function: GO:0004175 - endopeptidase activity Inferred from experiment [Keiler95]
GO:0008233 - peptidase activity Inferred by computational analysis [UniProtGOA11a]
GO:0008236 - serine-type peptidase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment [Hara91]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a]

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

Essentiality data for prc knockouts: ?

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: 3.4.21.102

a protein[periplasmic space] + H2O[periplasmic space] <=> a peptide[periplasmic space] + a peptide[periplasmic space]

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.


Sequence Features

Feature Class Location Citations Comment
Signal-Sequence 1 -> 22
[UniProt10]
UniProt: Non-Experimental Qualifier: potential;
Chain 23 -> 682
[UniProt09]
UniProt: Tail-specific protease;
Conserved-Region 238 -> 322
[UniProt09]
UniProt: PDZ;
Sequence-Conflict 317
[Hara91, UniProt, 2010]
Alternate sequence: L → Q; UniProt: (in Ref. 1; BAA00577/BAA00578);
Mutagenesis-Variant 397
[Keiler95a, UniProt11]
Alternate sequence: G → A; UniProt: Loss of activity. Perturbs protein structure.
Mutagenesis-Variant 398
[Keiler95a, UniProt11]
Alternate sequence: G → A; UniProt: Loss of activity. Perturbs protein structure.
Mutagenesis-Variant 452
[Keiler95a, UniProt11]
Alternate sequence: S → C; UniProt: Reduces activity by over 90%.
Alternate sequence: S → A; UniProt: Loss of activity.
Active-Site 452
[Keiler95a, UniProt11]
UniProt: Charge relay system.
Mutagenesis-Variant 455
[Keiler95a, UniProt11]
Alternate sequence: E → A; UniProt: Loss of activity. Perturbs protein structure.
Mutagenesis-Variant 463
[Keiler95a, UniProt11]
Alternate sequence: D → N; UniProt: Reduces activity by 90%.
Alternate sequence: D → A; UniProt: Loss of activity.
Active-Site 463
[UniProt10]
UniProt: Charge relay system; Non-Experimental Qualifier: probable;
Mutagenesis-Variant 474
[Keiler95a, UniProt11]
Alternate sequence: T → A; UniProt: Loss of activity. Perturbs protein structure.
Mutagenesis-Variant 477
[Keiler95a, UniProt11]
Alternate sequence: K → R; UniProt: Loss of activity. Perturbs protein structure.
Alternate sequence: K → H; UniProt: Loss of activity. No apparent effect on protein structure.
Alternate sequence: K → A; UniProt: Loss of activity. No apparent effect on protein structure.
Active-Site 477
[Keiler95a, UniProt11]
UniProt: Charge relay system.


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b1830 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10760; confirmed by SwissProt match.


References

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

Beebe00: Beebe KD, Shin J, Peng J, Chaudhury C, Khera J, Pei D (2000). "Substrate recognition through a PDZ domain in tail-specific protease." Biochemistry 39(11);3149-55. PMID: 10715137

Byrne14: Byrne RT, Chen SH, Wood EA, Cabot EL, Cox MM (2014). "Surviving extreme exposure to ionizing radiation: Escherichia coli genes and pathways." J Bacteriol. PMID: 25049088

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

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

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

Keiler95a: Keiler KC, Sauer RT (1995). "Identification of active site residues of the Tsp protease." J Biol Chem 270(48);28864-8. PMID: 7499412

Keiler96: Keiler KC, Waller PR, Sauer RT (1996). "Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA." Science 271(5251);990-3. PMID: 8584937

Keiler96a: Keiler KC, Sauer RT (1996). "Sequence determinants of C-terminal substrate recognition by the Tsp protease." J Biol Chem 271(5);2589-93. PMID: 8576225

Lee88: Lee YS, Park SC, Goldberg AL, Chung CH (1988). "Protease So from Escherichia coli preferentially degrades oxidatively damaged glutamine synthetase." J Biol Chem 263(14);6643-6. PMID: 2896198

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

Park88a: Park JH, Lee YS, Chung CH, Goldberg AL (1988). "Purification and characterization of protease Re, a cytoplasmic endoprotease in Escherichia coli." J Bacteriol 170(2);921-6. PMID: 2892828

Roseman87: Roseman JE, Levine RL (1987). "Purification of a protease from Escherichia coli with specificity for oxidized glutamine synthetase." J Biol Chem 262(5);2101-10. PMID: 2880842

Seoane92: Seoane A, Sabbaj A, McMurry LM, Levy SB (1992). "Multiple antibiotic susceptibility associated with inactivation of the prc gene." J Bacteriol 174(23);7844-7. PMID: 1447154

Silber92: Silber KR, Keiler KC, Sauer RT (1992). "Tsp: a tail-specific protease that selectively degrades proteins with nonpolar C termini." Proc Natl Acad Sci U S A 89(1);295-9. PMID: 1729701

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

UniProt, 2010: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."


Report Errors or Provide Feedback
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 18.5 on Sat Nov 22, 2014, biocyc13.