Escherichia coli K-12 substr. MG1655 Enzyme: protein-tyrosine kinase

Gene: wzc Accession Numbers: G7105 (EcoCyc), b2060, ECK2054

Regulation Summary Diagram: ?

Regulation summary diagram for wzc

Component of: capsular polysaccharide export apparatus

Wzc is a protein-tyrosine kinase that catalyzes autophosphorylation on tyrosine; phosphorylated Wzc can be dephosphorylated by Wzb [Vincent99, Soutourina01]. Autophosphorylation negatively regulates colanic acid biosynthesis [Vincent00]. However, both the phosphorylated and the nonphosphorylated forms of Wzc are required for wild-type synthesis of colanic acid [Obadia07]. Wzc also catalyzes phosphorylation of Ugd (Ugd, an enzyme of colanic acid biosynthesis), and this phosphorylation stimulates Ugd activity [Grangeasse03].

Wzc consists of an N-terminal domain with two transmembrane α-helices separated by a periplasmic region, and a C-terminal cytoplasmic domain containing six phosphorylation sites [Grangeasse02, Doublet02]. The N-terminal membrane domain appears to have no effect on the extent of phosphorylation of the C-terminal domain [Grangeasse02]. Tyr569 in the C-terminal domain is the substrate for intramolecular autophosphorylation; phosphorylation of this residue activates the kinase activity of Wzc, enabling it to catalyze intermolecular phosphorylation of tyrosine residues 708, 710, 711, 713, and 715 in the C-terminal tyrosine cluster of Wzc [Grangeasse02] and toward Ugd [Grangeasse03]. A Walker A and B ATP-binding motif is present in the C-terminal domain, and Wzc exhibits an ATPase activity that is regulated by intramolecular autophosphorylation [Soulat07].

The C-terminal region mediates formation of homomultimers [Doublet02].

A wzc null mutant does not produce colanic acid [Vincent00].

Involvement of Wzc in production of the capsule was shown in other E. coli strains, including O9a:K30 [Rahn99, Drummelsmith99, Wugeditsch01, Paiment02]. Cryo-EM experiments show that Wzc from a K30 strain forms homotetramers [Collins06], and Wza and Wzc form a complex [Collins07]. E. coli K-12 Wzc can rescue K30 capsule expression in a mutant O9a:K30 strain only in combination with the cognate K-12 Wza protein [Reid05].

Review: [Whitfield06]

Gene Citations: [Rhodius05, Stout96, Ebel99]

Locations: inner membrane

Map Position: [2,131,514 <- 2,133,676] (45.94 centisomes, 165°)
Length: 2163 bp / 720 aa

Molecular Weight of Polypeptide: 79.343 kD (from nucleotide sequence), 80.0 kD (experimental) [Vincent00 ]

Unification Links: ASAP:ABE-0006819 , DIP:DIP-28075N , EchoBASE:EB3338 , EcoGene:EG13568 , EcoliWiki:b2060 , Mint:MINT-8293229 , ModBase:P76387 , OU-Microarray:b2060 , PortEco:wzc , PR:PRO_000024223 , Pride:P76387 , Protein Model Portal:P76387 , RefSeq:NP_416564 , RegulonDB:G7105 , SMR:P76387 , String:511145.b2060 , UniProt:P76387

Relationship Links: InterPro:IN-FAMILY:IPR003856 , InterPro:IN-FAMILY:IPR005702 , InterPro:IN-FAMILY:IPR025669 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:3LA6 , Pfam:IN-FAMILY:PF02706 , Pfam:IN-FAMILY:PF13614

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for wzc

GO Terms:

Biological Process: GO:0009242 - colanic acid biosynthetic process Inferred from experiment [Vincent00]
GO:0018108 - peptidyl-tyrosine phosphorylation Inferred from experiment [Grangeasse02]
GO:0038083 - peptidyl-tyrosine autophosphorylation Inferred from experiment [Vincent99]
GO:0000271 - polysaccharide biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009103 - lipopolysaccharide biosynthetic process Inferred by computational analysis [GOA01]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11]
GO:0045226 - extracellular polysaccharide biosynthetic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0004713 - protein tyrosine kinase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11, Vincent99]
GO:0016887 - ATPase activity Inferred from experiment [Soulat07]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Daley05]
GO:0005887 - integral component of plasma membrane Inferred from experiment [Doublet02]
GO:0016020 - membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Vincent00]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11]

MultiFun Terms: information transfer protein related posttranslational modification
metabolism biosynthesis of macromolecules (cellular constituents) colanic acid (M antigen)

Essentiality data for wzc knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Enzymatic reaction of: tyrosine kinase

Synonyms: protein-tyrosine kinase, ATP:protein-tyrosine O-phosphotransferase

EC Number:

ATP + a [protein]-L-tyrosine <=> ADP + a [protein]-L-tyrosine phosphate + H+

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 favored in the direction shown.

Citations: [Soutourina01, Grangeasse03]

Subunit of: capsular polysaccharide export apparatus

Subunit composition of capsular polysaccharide export apparatus = [Wza]8[Wzc]4
         lipoprotein required for capsular polysaccharide translocation through the outer membrane = Wza (extended summary available)
         protein-tyrosine kinase = Wzc (extended summary available)

Citations: [Collins07]

Created 11-Apr-2007 by Johnson A , TIGR

Sequence Features

Protein sequence of protein-tyrosine kinase with features indicated

Feature Class Location Citations Comment
Transmembrane-Region 32 -> 52
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 425 -> 445
UniProt: Helical;; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 467
[Grangeasse02, UniProt15]
UniProt: No loss of autophosphorylation.
Mutagenesis-Variant 491
[Grangeasse02, UniProt15]
UniProt: No loss of autophosphorylation.
Mutagenesis-Variant 540
[Grangeasse02, UniProt15]
UniProt: Loss of autophosphorylation.
Mutagenesis-Variant 569
[Grangeasse02, UniProt15]
UniProt: Loss of autophosphorylation.
Phosphorylation-Modification 569
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine; by autocatalysis.
Mutagenesis-Variant 636
[Grangeasse02, UniProt15]
UniProt: No loss of autophosphorylation.
Mutagenesis-Variant 668
[Grangeasse02, UniProt15]
UniProt: No loss of autophosphorylation.
Phosphorylation-Modification 708
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine.
Phosphorylation-Modification 710
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine.
Phosphorylation-Modification 711
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine.
Phosphorylation-Modification 713
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine.
Phosphorylation-Modification 715
[Grangeasse03, UniProt15]
UniProt: Phosphotyrosine.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
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

Collins06: Collins RF, Beis K, Clarke BR, Ford RC, Hulley M, Naismith JH, Whitfield C (2006). "Periplasmic protein-protein contacts in the inner membrane protein Wzc form a tetrameric complex required for the assembly of Escherichia coli group 1 capsules." J Biol Chem 281(4);2144-50. PMID: 16172129

Collins07: Collins RF, Beis K, Dong C, Botting CH, McDonnell C, Ford RC, Clarke BR, Whitfield C, Naismith JH (2007). "The 3D structure of a periplasm-spanning platform required for assembly of group 1 capsular polysaccharides in Escherichia coli." Proc Natl Acad Sci U S A 104(7);2390-5. PMID: 17283336

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

Doublet02: Doublet P, Grangeasse C, Obadia B, Vaganay E, Cozzone AJ (2002). "Structural organization of the protein-tyrosine autokinase Wzc within Escherichia coli cells." J Biol Chem 277(40);37339-48. PMID: 12138098

Drummelsmith99: Drummelsmith J, Whitfield C (1999). "Gene products required for surface expression of the capsular form of the group 1 K antigen in Escherichia coli (O9a:K30)." Mol Microbiol 31(5);1321-32. PMID: 10200954

Ebel99: Ebel W, Trempy JE (1999). "Escherichia coli RcsA, a positive activator of colanic acid capsular polysaccharide synthesis, functions to activate its own expression." J Bacteriol 1999;181(2);577-84. PMID: 9882673

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

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grangeasse02: Grangeasse C, Doublet P, Cozzone AJ (2002). "Tyrosine phosphorylation of protein kinase Wzc from Escherichia coli K12 occurs through a two-step process." J Biol Chem 277(9);7127-35. PMID: 11751920

Grangeasse03: Grangeasse C, Obadia B, Mijakovic I, Deutscher J, Cozzone AJ, Doublet P (2003). "Autophosphorylation of the Escherichia coli protein kinase Wzc regulates tyrosine phosphorylation of Ugd, a UDP-glucose dehydrogenase." J Biol Chem 278(41);39323-9. PMID: 12851388

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

Obadia07: Obadia B, Lacour S, Doublet P, Baubichon-Cortay H, Cozzone AJ, Grangeasse C (2007). "Influence of tyrosine-kinase Wzc activity on colanic acid production in Escherichia coli K12 cells." J Mol Biol 367(1);42-53. PMID: 17254603

Paiment02: Paiment A, Hocking J, Whitfield C (2002). "Impact of phosphorylation of specific residues in the tyrosine autokinase, Wzc, on its activity in assembly of group 1 capsules in Escherichia coli." J Bacteriol 184(23);6437-47. PMID: 12426330

Rahn99: Rahn A, Drummelsmith J, Whitfield C (1999). "Conserved organization in the cps gene clusters for expression of Escherichia coli group 1 K antigens: relationship to the colanic acid biosynthesis locus and the cps genes from Klebsiella pneumoniae." J Bacteriol 181(7);2307-13. PMID: 10094716

Reid05: Reid AN, Whitfield C (2005). "functional analysis of conserved gene products involved in assembly of Escherichia coli capsules and exopolysaccharides: evidence for molecular recognition between Wza and Wzc for colanic acid biosynthesis." J Bacteriol 187(15);5470-81. PMID: 16030241

Rhodius05: Rhodius VA, Suh WC, Nonaka G, West J, Gross CA (2005). "Conserved and variable functions of the sigmaE stress response in related genomes." PLoS Biol 4(1);e2. PMID: 16336047

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Soulat07: Soulat D, Jault JM, Geourjon C, Gouet P, Cozzone AJ, Grangeasse C (2007). "Tyrosine-kinase Wzc from Escherichia coli possesses an ATPase activity regulated by autophosphorylation." FEMS Microbiol Lett 274(2);252-9. PMID: 17627778

Soutourina01: Soutourina J, Blanquet S, Plateau P (2001). "Role of D-cysteine desulfhydrase in the adaptation of Escherichia coli to D-cysteine." J Biol Chem 276(44);40864-72. PMID: 11527960

Stout96: Stout V (1996). "Identification of the promoter region for the colanic acid polysaccharide biosynthetic genes in Escherichia coli K-12." J Bacteriol 178(14);4273-80. PMID: 8763957

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

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

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

Vincent00: Vincent C, Duclos B, Grangeasse C, Vaganay E, Riberty M, Cozzone AJ, Doublet P (2000). "Relationship between exopolysaccharide production and protein-tyrosine phosphorylation in gram-negative bacteria." J Mol Biol 304(3);311-21. PMID: 11090276

Vincent99: Vincent C, Doublet P, Grangeasse C, Vaganay E, Cozzone AJ, Duclos B (1999). "Cells of Escherichia coli contain a protein-tyrosine kinase, Wzc, and a phosphotyrosine-protein phosphatase, Wzb." J Bacteriol 181(11);3472-7. PMID: 10348860

Whitfield06: Whitfield C (2006). "Biosynthesis and assembly of capsular polysaccharides in Escherichia coli." Annu Rev Biochem 75;39-68. PMID: 16756484

Wugeditsch01: Wugeditsch T, Paiment A, Hocking J, Drummelsmith J, Forrester C, Whitfield C (2001). "Phosphorylation of Wzc, a tyrosine autokinase, is essential for assembly of group 1 capsular polysaccharides in Escherichia coli." J Biol Chem 276(4);2361-71. PMID: 11053445

Other References Related to Gene Regulation

Gottesman91: Gottesman S, Stout V (1991). "Regulation of capsular polysaccharide synthesis in Escherichia coli K12." Mol Microbiol 1991;5(7);1599-606. PMID: 1943696

Kamenšek13: Kamenšek S, Žgur-Bertok D (2013). "Global transcriptional responses to the bacteriocin colicin M in Escherichia coli." BMC Microbiol 13;42. PMID: 23421615

Wehland00: Wehland M, Bernhard F (2000). "The RcsAB box. Characterization of a new operator essential for the regulation of exopolysaccharide biosynthesis in enteric bacteria." J Biol Chem 2000;275(10);7013-20. PMID: 10702265

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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