Escherichia coli K-12 substr. MG1655 Enzyme: hydroxyisourate hydrolase / transthyretin-related protein

Gene: yedX Accession Numbers: G7058 (EcoCyc), b1970, ECK1966

Synonyms: hiuH, transthyretin-like protein (TLP), transthyretin-related protein (TRP)

Regulation Summary Diagram

Regulation summary diagram for yedX

Subunit composition of hydroxyisourate hydrolase / transthyretin-related protein = [YedX]4
         conserved protein = YedX

YedX belongs to the family of transthyretin-related proteins (TRP). Transthyretin is a transport protein in extracellular fluids of vertebrates, where it distributes thyroid hormones [Richardson02]. YedX is othologous with Bacillus subtilis PucM, which functions to facilitate the hydrolysis of 5-hydroxyisourate (HIU), the end product of the uricase reaction; purified YedX has 5-hydroxyisourate hydrolase (HIUH) activity [Lee05d]

The physiological significance of HIUH activity in E. coli is unclear. The source of HIU is not known; E. coli degrades purines to form uric acid (see guanosine nucleotides degradation III and adenosine nucleotides degradation II), which is a good source of nitrogen in many organisms, but uricase activity has not been identified in E.coli. Alternatively, [Hennebry06] suggests that uric acid functions as an antioxidant in enterobacteria and that the oxidative (nonenzymatic) decomposition of uric acid would also generate HIU which can spontaneously decompose into, and react with, a variety of free radical compounds. Enzymatic removal of 5-HIU (by periplasmic YedX) would thus prevent accumulation of potentially toxic compounds.

YedX contains a cleaved signal sequence and may be located in the periplasm. The protein is a tetramer in solution. E. coli YedX does not bind the thyroid hormones thyroxine and triiodo-thyronine [Eneqvist03]. Purified YedX forms amyloidogenic fibrils at pH 5.8 - pH 6.8 with stirring for 3 days [Santos08] and upon heating at 65°C at pH 7.4 for 3 days without stirring [Lundberg09]. Purified YedX maintains its tetrameric structure at low pH - separating into monomers at pH 3 - and has a melting temperature (TM) of 66.7°C [Lundberg09]

Crystal structures of YedX have been determined at 1.65 and 2.1 Å resolution. The structures are similar to eukaryotic transthyretins. Zinc ions are located at the putative ligand binding site, although zinc is absent from the purified recombinant protein [Lundberg06].

Review: [Richardson02]

Locations: periplasmic space

Map Position: [2,038,956 -> 2,039,369] (43.93 centisomes, 158°)
Length: 414 bp / 137 aa

Molecular Weight of Polypeptide: 15.46 kD (from nucleotide sequence), 16.0 kD (experimental) [Santos08]

Molecular Weight of Multimer: 50 kD (experimental) [Eneqvist03]

pI: 8.4 [Eneqvist03]

Unification Links: ASAP:ABE-0006537, DIP:DIP-11854N, EchoBASE:EB3799, EcoGene:EG14046, EcoliWiki:b1970, ModBase:P76341, OU-Microarray:b1970, PortEco:yedX, Protein Model Portal:P76341, RefSeq:NP_416479, RegulonDB:G7058, SMR:P76341, String:511145.b1970, UniProt:P76341

Relationship Links: InterPro:IN-FAMILY:IPR000895, InterPro:IN-FAMILY:IPR014306, InterPro:IN-FAMILY:IPR023416, InterPro:IN-FAMILY:IPR023418, InterPro:IN-FAMILY:IPR023419, PDB:Structure:2G2N, PDB:Structure:2G2P, PDB:Structure:2IGL, Pfam:IN-FAMILY:PF00576, Prints:IN-FAMILY:PR00189, Prosite:IN-FAMILY:PS00768, Prosite:IN-FAMILY:PS00769, Smart:IN-FAMILY:SM00095

Gene-Reaction Schematic

Gene-Reaction Schematic

Genetic Regulation Schematic

Genetic regulation schematic for yedX

GO Terms:
Biological Process:
Inferred by computational analysisGO:0006144 - purine nucleobase metabolic process [UniProtGOA11a, GOA01a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0033971 - hydroxyisourate hydrolase activity [Lee05d, GOA01, GOA01a]
Inferred from experimentGO:0042802 - identical protein binding [Eneqvist03, Santos08]
Inferred by computational analysisGO:0016787 - hydrolase activity [UniProtGOA11a]
Cellular Component:
Inferred by computational analysisGO:0030288 - outer membrane-bounded periplasmic space [DiazMejia09]
Inferred by computational analysisGO:0042597 - periplasmic space [UniProtGOA11, UniProtGOA11a]

Gene Class: ORFsConserved-ORFs

Essentiality data for yedX knockouts:

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

Created 31-May-2006 by Keseler I, SRI International
Curated 31-May-2006 by Keseler I, SRI International
Last-Curated 28-Feb-2016 by Mackie A, Macquarie University

Enzymatic reaction of: 5-hydroxyisourate hydrolase (hydroxyisourate hydrolase / transthyretin-related protein)

Inferred from experiment

EC Number:

5-hydroxyisourate[periplasmic space] + H2O[periplasmic space] → 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline[periplasmic space] + H+[periplasmic space]

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Citations: [Lee05d]

Sequence Features

Protein sequence of conserved protein with features indicated

Feature Class Location Citations Comment
Signal-Sequence 1 -> 23
Inferred from experiment[Eneqvist03, Eneqvist03]
Chain 24 -> 137
Author statement[UniProt15]
UniProt: 5-hydroxyisourate hydrolase.
Pfam PF00576 29 -> 136
Inferred by computational analysis[Finn14]
Transthyretin : HIUase/Transthyretin family [More...]
Amino-Acid-Sites-That-Bind 32
Inferred by computational analysis[UniProt15]
UniProt: Substrate.
Amino-Acid-Sites-That-Bind 70
Inferred by computational analysis[UniProt15]
UniProt: Substrate.
Conserved-Region 134 -> 137
Inferred by computational analysis[Lee05d]
(transthyretin-related proteins) TRP motif
Amino-Acid-Sites-That-Bind 134
Inferred by computational analysis[UniProt15]
UniProt: Substrate.

Gene Local Context (not to scale -- see Genome Browser for correct scale)

Transcription Unit

Transcription-unit diagram


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

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

Eneqvist03: Eneqvist T, Lundberg E, Nilsson L, Abagyan R, Sauer-Eriksson AE (2003). "The transthyretin-related protein family." Eur J Biochem 270(3);518-32. PMID: 12542701

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

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, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Hennebry06: Hennebry SC, Wright HM, Likic VA, Richardson SJ (2006). "Structural and functional evolution of transthyretin and transthyretin-like proteins." Proteins 64(4);1024-45. PMID: 16783790

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

Lee05d: Lee Y, Lee DH, Kho CW, Lee AY, Jang M, Cho S, Lee CH, Lee JS, Myung PK, Park BC, Park SG (2005). "Transthyretin-related proteins function to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction." FEBS Lett 579(21);4769-74. PMID: 16098976

Lundberg06: Lundberg E, Backstrom S, Sauer UH, Sauer-Eriksson AE (2006). "The transthyretin-related protein: Structural investigation of a novel protein family." J Struct Biol 155(3):445-57. PMID: 16723258

Lundberg09: Lundberg E, Olofsson A, Westermark GT, Sauer-Eriksson AE (2009). "Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein." FEBS J 276(7);1999-2011. PMID: 19250316

Richardson02: Richardson SJ (2002). "The evolution of transthyretin synthesis in vertebrate liver, in primitive eukaryotes and in bacteria." Clin Chem Lab Med 40(12);1191-9. PMID: 12553419

Santos08: Santos SD, Costa R, Teixeira PF, Gottesman M, Cardoso I, Saraiva MJ (2008). "Amyloidogenic properties of transthyretin-like protein (TLP) from Escherichia coli." FEBS Lett 582(19);2893-8. PMID: 18656475

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." 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."

Other References Related to Gene Regulation

Huerta03: Huerta AM, Collado-Vides J (2003). "Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals." J Mol Biol 333(2);261-78. PMID: 14529615

Urano15: Urano H, Umezawa Y, Yamamoto K, Ishihama A, Ogasawara H (2015). "Cooperative regulation of the common target genes between H2O2-sensing YedVW and Cu2+-sensing CusSR in Escherichia coli." Microbiology 161(Pt 4);729-38. PMID: 25568260

Yang12a: Yang C, Huang TW, Wen SY, Chang CY, Tsai SF, Wu WF, Chang CH (2012). "Genome-wide PhoB binding and gene expression profiles reveal the hierarchical gene regulatory network of phosphate starvation in Escherichia coli." PLoS One 7(10);e47314. PMID: 23071782

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 Pathway Tools version 20.0 (software by SRI International) on Thu May 5, 2016, BIOCYC13A.