Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaE (IPR011317)

Short name: Prd_NiFe_hyd_3_EhaE

Overlapping homologous superfamilies


Family relationships



[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster [PMID: 15119826].

Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family [PMID: 15168611, PMID: 16645307]. Members of this subgroup include:

  • Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coli
  • CO-induced hydrogenase (Coo) from Rhodospirillum rubrum
  • Mbh hydrogenase from Pyrococcus furiosus
  • Eha and Ehb hydrogenases from Methanothermobacter species
  • Ech hydrogenase from Methanosarcina barkeri

Energy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe] hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe] hydrogenases function as ion pumps.

Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S] polyferredoxin, ten other predicted integral membrane proteins (EhaA IPR011306, EhaB IPR011314, EhaC IPR011316, EhaD IPR011308, EhaE IPR011317, EhaF IPR011313, EhaG IPR011311, EhaI IPR011318, EhaK IPR011319, EhaL IPR011305) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [PMID: 10491142]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.

Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar eha operon structure.

This entry represents small membrane proteins that are predicted to be the EhaE transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.