PROSITE documentation PDOC00175
2Fe-2S ferredoxin-type iron-sulfur binding domain signature and profile


Ferredoxins are small, acidic, electron transfer proteins that are ubiquitous in biological redox systems. They have either 4Fe-4S, 3Fe-4S, or 2Fe-2S cluster. Among them, ferredoxin with one 2Fe-2S cluster per molecule are present in plants, animals, and bacteria, and form a distinct 2Fe-Ferredoxin family [1,2]. They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe-2S cluster is ligated. This conserved region is also found as a domain in various metabolic enzymes.

Several structures of the 2Fe-2S ferredoxin domain have been determined (see for example <PDB:4FXC>) [3]. The domain is classified as a β-grasp which is characterized as having a β-sheet comprised of four β-strands and one α-helix flanking the sheet [4]. The two Fe atoms are coordinated tetrahedrally by the two inorganic S atoms and four cysteinyl S atoms.

Some proteins that contains a 2Fe-2S ferredoxin-type domain are listed below:

  • Ferredoxin from photosynthetic organisms; namely plants and algae where it is located in the chloroplast or cyanelle; and cyanobacteria.
  • Ferredoxin from archaebacteria of the Halobacterium genus.
  • Ferredoxin IV (gene pftA) and V (gene fdxD) from Rhodobacter capsulatus.
  • Ferredoxin in the toluene degradation operon (gene xylT) and naphthalene degradation operon (gene nahT) of Pseudomonas putida.
  • Hypothetical Escherichia coli protein yfaE.
  • The N-terminal domain of the bifunctional ferredoxin/ferredoxin reductase electron transfer component of the benzoate 1,2-dioxygenase complex (gene benC) from Acinetobacter calcoaceticus, the toluene 4-monooxygenase complex (gene tmoF), the toluate 1,2-dioxygenase system (gene xylZ), and the xylene monooxygenase system (gene xylA) from Pseudomonas.
  • The N-terminal domain of phenol hydroxylase protein p5 (gene dmpP) from Pseudomonas Putida.
  • The N-terminal domain of methane monooxygenase component C (gene mmoC) from Methylococcus capsulatus .
  • The C-terminal domain of the vanillate degradation pathway protein vanB in a Pseudomonas species.
  • The N-terminal domain of bacterial fumarate reductase iron-sulfur protein (gene frdB).
  • The N-terminal domain of CDP-6-deoxy-3,4-glucoseen reductase (gene ascD) from Yersinia pseudotuberculosis.
  • The central domain of eukaryotic succinate dehydrogenase (ubiquinone) iron- sulfur protein.
  • The N-terminal domain of eukaryotic xanthine dehydrogenase.
  • The N-terminal domain of eukaryotic aldehyde oxidase.

Three of the four conserved cysteines are clustered together in the same region of the protein. Our signature pattern spans that iron-sulfur binding region. We also developed a profile that covers the whole domain.


Ferredoxins from the adrenodoxin subfamily are slightly divergent and are not picked up by our pattern (but they are recognized by the profile). We have thus developed a second pattern specific for this subfamily (see <PDOC00642>).

Last update:

March 2005 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

2FE2S_FER_2, PS51085; 2Fe-2S ferredoxin-type iron-sulfur binding domain profile  (MATRIX)

2FE2S_FER_1, PS00197; 2Fe-2S ferredoxin-type iron-sulfur binding region signature  (PATTERN)


1AuthorsMeyer J.
SourceTrends Ecol. Evol. 3:222-226(1988).

2AuthorsHarayama S. Polissi A. Rekik M.
TitleDivergent evolution of chloroplast-type ferredoxins.
SourceFEBS Lett. 285:85-88(1991).
PubMed ID2065785

3AuthorsFukuyama K. Ueki N. Nakamura H. Tsukihara T. Matsubara H.
TitleTertiary structure of [2Fe-2S] ferredoxin from Spirulina platensis refined at 2.5 A resolution: structural comparisons of plant-type ferredoxins and an electrostatic potential analysis.
SourceJ. Biochem. 117:1017-1023(1995).
PubMed ID8586613

4AuthorsOverington J.P.
SourceCurr. Opin. Struct. Biol. 2:394-401(1992).

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