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Escherichia coli K-12 substr. MG1655 Polypeptide: accessory protein for nickel incorporation into hydrogenase 3

Gene: hypA Accession Numbers: EG10483 (EcoCyc), b2726, ECK2721

Regulation Summary Diagram: ?

Component of: HypA-HypB heterodimer (summary available)

HypA and its homolog, HybF, are involved in the maturation of hydrogenase isozymes. A mutation in hypA almost completely abolishes hydrogenase 3 activity [Jacobi92]. HypA is specifically involved in hydrogenase 3 maturation, while HybF is involved in the maturation of hydrogenase 1 and 2; HypA and HybF can only partially substitute for each other [Hube02]. The presence of high levels of nickel can phenotypically rescue hypA and hybF mutants and a triple hypA hypB hybF mutant to a low level [Hube02, Blokesch04].

HypA has both a nanomolar-affinity Zn2+ binding site and a micromolar-affinity Ni2+ binding site. The Zn2+ binding site appears to play a structural role; Zn2+ content modulates oligomeric complex formation [Atanassova05].

Interactions of HypA with other proteins have been shown to be important for hydrogenase 3 maturation. HypA and HypB, another accessory protein for hydrogenase maturation, interact directly [Atanassova05, Chan12], and HypA by itself can interact with the large subunit of hydrogenase 3, HycE. HypA may thus act as a scaffold for assembly of HypB and SlyD, the proteins responsible for Ni2+ insertion to [NiFe] hydrogenase 3 [Chan11].

HypA: hydrogenase, pleiotropic

Review: [Forzi07]

Gene Citations: [Schlensog90, Hopper94]

Locations: cytosol, inner membrane

Map Position: [2,848,669 -> 2,849,019] (61.4 centisomes)
Length: 351 bp / 116 aa

Molecular Weight of Polypeptide: 13.168 kD (from nucleotide sequence), 14.0 kD (experimental) [Lutz91 ]

Unification Links: ASAP:ABE-0008958 , CGSC:33104 , DIP:DIP-48022N , EchoBASE:EB0478 , EcoGene:EG10483 , EcoliWiki:b2726 , OU-Microarray:b2726 , PortEco:hypA , PR:PRO_000022972 , Protein Model Portal:P0A700 , RefSeq:NP_417206 , RegulonDB:EG10483 , SMR:P0A700 , String:511145.b2726 , UniProt:P0A700

Relationship Links: InterPro:IN-FAMILY:IPR000688 , InterPro:IN-FAMILY:IPR020538 , Pfam:IN-FAMILY:PF01155 , Prosite:IN-FAMILY:PS01249

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0051604 - protein maturation Inferred from experiment [Hube02]
GO:0006464 - cellular protein modification process Inferred by computational analysis [GOA06, GOA01a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Atanassova05, Chan11]
GO:0008270 - zinc ion binding Inferred from experiment [Atanassova05]
GO:0016151 - nickel cation binding Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Atanassova05]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0031234 - extrinsic component of cytoplasmic side of plasma membrane Inferred from experiment [Chan11]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism energy metabolism, carbon anaerobic respiration

Essentiality data for hypA 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]

Last-Curated ? 21-Mar-2012 by Keseler I , SRI International

Subunit of: HypA-HypB heterodimer

Subunit composition of HypA-HypB heterodimer = [HypA][HypB]
         accessory protein for nickel incorporation into hydrogenase 3 = HypA (extended summary available)
         accessory protein for nickel incorporation into hydrogenase isoenzymes = HypB (extended summary available)

HypA and HypB form a heterodimer [Atanassova05].

Citations: [Chan12]

Sequence Features

Feature Class Location Citations Comment
Metal-Binding-Site 2
UniProt: Nickel; Non-Experimental Qualifier: potential;
Metal-Binding-Site 73
UniProt: Nickel; Non-Experimental Qualifier: potential;
Metal-Binding-Site 76
UniProt: Nickel; Non-Experimental Qualifier: potential;
Metal-Binding-Site 90
UniProt: Nickel; Non-Experimental Qualifier: potential;
Metal-Binding-Site 93
UniProt: Nickel; Non-Experimental Qualifier: potential;

Gene Local Context (not to scale): ?

Transcription Units:


10/20/97 Gene b2726 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10483; confirmed by SwissProt match.


Atanassova05: Atanassova A, Zamble DB (2005). "Escherichia coli HypA is a zinc metalloprotein with a weak affinity for nickel." J Bacteriol 187(14);4689-97. PMID: 15995183

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

Blokesch04: Blokesch M, Rohrmoser M, Rode S, Bock A (2004). "HybF, a zinc-containing protein involved in NiFe hydrogenase maturation." J Bacteriol 186(9);2603-11. PMID: 15090500

Chan11: Chan Chung KC, Zamble DB (2011). "Protein interactions and localization of the Escherichia coli accessory protein HypA during nickel insertion to [NiFe] hydrogenase." J Biol Chem 286(50);43081-90. PMID: 22016389

Chan12: Chan KH, Lee KM, Wong KB (2012). "Interaction between Hydrogenase Maturation Factors HypA and HypB Is Required for [NiFe]-Hydrogenase Maturation." PLoS One 7(2);e32592. PMID: 22384275

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

Forzi07: Forzi L, Sawers RG (2007). "Maturation of [NiFe]-hydrogenases in Escherichia coli." Biometals 20(3-4):565-78. PMID: 17216401

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."

Hopper94: Hopper S, Babst M, Schlensog V, Fischer HM, Hennecke H, Bock A (1994). "Regulated expression in vitro of genes coding for formate hydrogenlyase components of Escherichia coli." J Biol Chem 1994;269(30);19597-604. PMID: 8034728

Hube02: Hube M, Blokesch M, Bock A (2002). "Network of hydrogenase maturation in Escherichia coli: role of accessory proteins HypA and HybF." J Bacteriol 184(14);3879-85. PMID: 12081959

Jacobi92: Jacobi A, Rossmann R, Bock A (1992). "The hyp operon gene products are required for the maturation of catalytically active hydrogenase isoenzymes in Escherichia coli." Arch Microbiol 158(6);444-51. PMID: 1482271

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

Lutz91: Lutz S, Jacobi A, Schlensog V, Bohm R, Sawers G, Bock A (1991). "Molecular characterization of an operon (hyp) necessary for the activity of the three hydrogenase isoenzymes in Escherichia coli." Mol Microbiol 5(1);123-35. PMID: 1849603

Schlensog90: Schlensog V, Bock A (1990). "Identification and sequence analysis of the gene encoding the transcriptional activator of the formate hydrogenlyase system of Escherichia coli." Mol Microbiol 1990;4(8);1319-27. PMID: 2280686

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

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

Altuvia98: Altuvia S, Zhang A, Argaman L, Tiwari A, Storz G (1998). "The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding." EMBO J 17(20);6069-75. PMID: 9774350

Argaman00: Argaman L, Altuvia S (2000). "fhlA repression by OxyS RNA: kissing complex formation at two sites results in a stable antisense-target RNA complex." J Mol Biol 300(5);1101-12. PMID: 10903857

Leonhartsberger00: Leonhartsberger S, Ehrenreich A, Bock A (2000). "Analysis of the domain structure and the DNA binding site of the transcriptional activator FhlA." Eur J Biochem 267(12);3672-84. PMID: 10848985

Partridge09: Partridge JD, Bodenmiller DM, Humphrys MS, Spiro S (2009). "NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility." Mol Microbiol 73(4);680-94. PMID: 19656291

Salim10: Salim NN, Feig AL (2010). "An upstream Hfq binding site in the fhlA mRNA leader region facilitates the OxyS-fhlA interaction." PLoS One 5(9). PMID: 20927406

Schlensog94: Schlensog V, Lutz S, Bock A (1994). "Purification and DNA-binding properties of FHLA, the transcriptional activator of the formate hydrogenlyase system from Escherichia coli." J Biol Chem 1994;269(30);19590-6. PMID: 8034727

Zhang02a: Zhang A, Wassarman KM, Ortega J, Steven AC, Storz G (2002). "The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs." Mol Cell 9(1);11-22. PMID: 11804582

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 Thu Feb 26, 2015, biocyc13.