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435  structures 7547  species 0  interactions 46841  sequences 393  architectures

Family: Fer2 (PF00111)

Summary: 2Fe-2S iron-sulfur cluster binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Ferredoxin". More...

Ferredoxin Edit Wikipedia article

Ferredoxins (from Latin ferrum: iron + redox, often abbreviated "fd") are iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co. and applied to the "iron protein" first purified in 1962 by Mortenson, Valentine, and Carnahan from the anaerobic bacterium Clostridium pasteurianum.[1][2]

Another redox protein, isolated from spinach chloroplasts, was termed "chloroplast ferredoxin".[3] The chloroplast ferredoxin is involved in both cyclic and non-cyclic photophosphorylation reactions of photosynthesis. In non-cyclic photophosphorylation, ferredoxin is the last electron acceptor thus reducing the enzyme NADP+ reductase. It accepts electrons produced from sunlight-excited chlorophyll and transfers them to the enzyme ferredoxin: NADP+ oxidoreductase EC

Ferredoxins are small proteins containing iron and sulfur atoms organized as iron–sulfur clusters. These biological "capacitors" can accept or discharge electrons, with the effect of a change in the oxidation state of the iron atoms between +2 and +3. In this way, ferredoxin acts as an electron transfer agent in biological redox reactions.

Other bioinorganic electron transport systems include rubredoxins, cytochromes, blue copper proteins, and the structurally related Rieske proteins.

Ferredoxins can be classified according to the nature of their iron–sulfur clusters and by sequence similarity.

Fe2S2 ferredoxins

2Fe-2S iron-sulfur cluster binding domain
Structural representation of an Fe2S2 ferredoxin.
Pfam clanCL0486
OPM protein1kf6

Members of the 2Fe–2S ferredoxin superfamily (InterProIPR036010) have a general core structure consisting of beta(2)-alpha-beta(2), which includes putidaredoxin, terpredoxin, and adrenodoxin.[4][5][6][7] 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 and in multidomain proteins, such as aldehyde oxidoreductase (N-terminal), xanthine oxidase (N-terminal), phthalate dioxygenase reductase (C-terminal), succinate dehydrogenase iron–sulphur protein (N-terminal), and methane monooxygenase reductase (N-terminal).

Plant-type ferredoxins

One group of ferredoxins, originally found in chloroplast membranes, has been termed "chloroplast-type" or "plant-type" (InterProIPR010241). Its active center is a [Fe2S2] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved cysteine (Cys) residues.

In chloroplasts, Fe2S2 ferredoxins function as electron carriers in the photosynthetic electron transport chain and as electron donors to various cellular proteins, such as glutamate synthase, nitrite reductase and sulfite reductase. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase.

Thioredoxin-like ferredoxins

The Fe2S2 ferredoxin from Clostridium pasteurianum (Cp2FeFd; P07324) has been recognized as distinct protein family on the basis of its amino acid sequence, spectroscopic properties of its iron–sulfur cluster and the unique ligand swapping ability of two cysteine ligands to the [Fe2S2] cluster. Although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of Cp2FeFd with the molybdenum-iron protein of nitrogenase has been revealed. Homologous ferredoxins from Azotobacter vinelandii (Av2FeFdI; P82802) and Aquifex aeolicus (AaFd; O66511) have been characterized. The crystal structure of AaFd has been solved. AaFd exists as a dimer. The structure of AaFd monomer is different from other Fe2S2 ferredoxins. The fold belongs to the α+β class, with first four β-strands and two α-helices adopting a variant of the thioredoxin fold.[8] UniProt categorizes these as the "2Fe2S Shethna-type ferredoxin" family.[9]

Adrenodoxin-type ferredoxins

ferredoxin 1
Crystal structure of human ferredoxin-1 (FDX1).[10]
Alt. symbolsFDX
NCBI gene2230
Other data
LocusChr. 11 q22.3

Adrenodoxin (adrenal ferredoxin; InterProIPR001055), putidaredoxin, and terpredoxin make up a family of soluble Fe2S2 proteins that act as single electron carriers, mainly found in eukaryotic mitochondria and Proteobacteria. The human variant of adrenodoxin is referred to as ferredoxin-1 and ferredoxin-2. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH:adrenodoxin reductase to membrane-bound cytochrome P450. In bacteria, putidaredoxin and terpredoxin transfer electrons between corresponding NADH-dependent ferredoxin reductases and soluble P450s.[11][12] The exact functions of other members of this family are not known, although Escherichia coli Fdx is shown to be involved in biogenesis of Fe–S clusters.[13] Despite low sequence similarity between adrenodoxin-type and plant-type ferredoxins, the two classes have a similar folding topology.

Ferredoxin-1 in humans participates in the synthesis of thyroid hormones. It also transfers electrons from adrenodoxin reductase to CYP11A1, a CYP450 enzyme responsible for cholesterol side chain cleavage. FDX-1 has the capability to bind to metals and proteins.[14] Ferredoxin-2 participates in heme A and iron–sulphur protein synthesis.[15]

Fe4S4 and Fe3S4 ferredoxins

The [Fe4S4] ferredoxins may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins.

Low- and high-potential ferredoxins are related by the following redox scheme:


The formal oxidation numbers of the iron ions can be [2Fe3+, 2Fe2+] or [1Fe3+, 3Fe2+] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe3+, 1Fe2+] or [2Fe3+, 2Fe2+].

Bacterial-type ferredoxins

3Fe-4S binding domain
Structural representation of an Fe3S4 ferredoxin.
OPM protein1kqf

A group of Fe4S4 ferredoxins, originally found in bacteria, has been termed "bacterial-type". Bacterial-type ferredoxins may in turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four cysteine residues that bind to a [Fe4S4] cluster. In Pyrococcus furiosus Fe4S4 ferredoxin, one of the conserved Cys residues is substituted with aspartic acid.

During the evolution of bacterial-type ferredoxins, intrasequence gene duplication, transposition and fusion events occurred, resulting in the appearance of proteins with multiple iron–sulfur centers. In some bacterial ferredoxins, one of the duplicated domains has lost one or more of the four conserved Cys residues. These domains have either lost their iron–sulfur binding property or bind to a [Fe3S4] cluster instead of a [Fe4S4] cluster[16] and dicluster-type.[17]

3-D structures are known for a number of monocluster and dicluster bacterial-type ferredoxins. The fold belongs to the α+β class, with 2-7 α-helices and four β-strands forming a barrel-like structure, and an extruded loop containing three "proximal" Cys ligands of the iron–sulfur cluster.

High-potential iron–sulfur proteins

High potential iron–sulfur proteins (HiPIPs) form a unique family of Fe4S4 ferredoxins that function in anaerobic electron transport chains. Some HiPIPs have a redox potential higher than any other known iron–sulfur protein (e.g., HiPIP from Rhodopila globiformis has a redox potential of ca. 450 mV). Several HiPIPs have so far been characterized structurally, their folds belonging to the α+β class. As in other bacterial ferredoxins, the [Fe4S4] unit forms a cubane-type cluster and is ligated to the protein via four Cys residues.

Human proteins from ferredoxin family


  1. ^ Mortenson LE, Valentine RC, Carnahan JE (June 1962). "An electron transport factor from Clostridium pasteurianum". Biochemical and Biophysical Research Communications. 7 (6): 448–52. doi:10.1016/0006-291X(62)90333-9. PMID 14476372.
  2. ^ Valentine RC (December 1964). "BACTERIAL FERREDOXIN". Bacteriological Reviews. 28: 497–517. PMC 441251. PMID 14244728.
  3. ^ Tagawa K, Arnon DI (August 1962). "Ferredoxins as electron carriers in photosynthesis and in the biological production and consumption of hydrogen gas". Nature. 195 (4841): 537–43. Bibcode:1962Natur.195..537T. doi:10.1038/195537a0. PMID 14039612.
  4. ^ Armengaud J, Sainz G, Jouanneau Y, Sieker LC (February 2001). "Crystallization and preliminary X-ray diffraction analysis of a [2Fe-2S] ferredoxin (FdVI) from Rhodobacter capsulatus". Acta Crystallographica Section D. 57 (Pt 2): 301–3. doi:10.1107/S0907444900017832. PMID 11173487.
  5. ^ Sevrioukova IF (April 2005). "Redox-dependent structural reorganization in putidaredoxin, a vertebrate-type [2Fe-2S] ferredoxin from Pseudomonas putida". Journal of Molecular Biology. 347 (3): 607–21. doi:10.1016/j.jmb.2005.01.047. PMID 15755454.
  6. ^ Mo H, Pochapsky SS, Pochapsky TC (April 1999). "A model for the solution structure of oxidized terpredoxin, a Fe2S2 ferredoxin from Pseudomonas". Biochemistry. 38 (17): 5666–75. CiteSeerX doi:10.1021/bi983063r. PMID 10220356.
  7. ^ Beilke D, Weiss R, Löhr F, Pristovsek P, Hannemann F, Bernhardt R, Rüterjans H (June 2002). "A new electron transport mechanism in mitochondrial steroid hydroxylase systems based on structural changes upon the reduction of adrenodoxin". Biochemistry. 41 (25): 7969–78. doi:10.1021/bi0160361. PMID 12069587.
  8. ^ Yeh AP, Ambroggio XI, Andrade SL, Einsle O, Chatelet C, Meyer J, Rees DC (September 2002). "High resolution crystal structures of the wild type and Cys-55-->Ser and Cys-59-->Ser variants of the thioredoxin-like [2Fe-2S] ferredoxin from Aquifex aeolicus". The Journal of Biological Chemistry. 277 (37): 34499–507. doi:10.1074/jbc.M205096200. PMID 12089152.
  9. ^ family:"2fe2s shethna type ferredoxin family"
  10. ^ PDB: 3P1M​; Chaikuad A, Johansson, C, Krojer, T, Yue, WW, Phillips, C, Bray, JE, Pike, ACW, Muniz, JRC, Vollmar, M, Weigelt, J, Arrowsmith, CH, Edwards, AM, Bountra, C, Kavanagh, K, Oppermann, U (2010). "Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur cluster". To be Published. doi:10.2210/pdb3p1m/pdb.
  11. ^ Peterson JA, Lorence MC, Amarneh B (April 1990). "Putidaredoxin reductase and putidaredoxin. Cloning, sequence determination, and heterologous expression of the proteins". The Journal of Biological Chemistry. 265 (11): 6066–73. PMID 2180940.
  12. ^ Peterson JA, Lu JY, Geisselsoder J, Graham-Lorence S, Carmona C, Witney F, Lorence MC (July 1992). "Cytochrome P-450terp. Isolation and purification of the protein and cloning and sequencing of its operon". The Journal of Biological Chemistry. 267 (20): 14193–203. PMID 1629218.
  13. ^ Tokumoto U, Takahashi Y (July 2001). "Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins". Journal of Biochemistry. 130 (1): 63–71. doi:10.1093/oxfordjournals.jbchem.a002963. PMID 11432781.
  14. ^ "Entrez Gene: FDX1 ferredoxin 1".
  15. ^ "FDX2 ferredoxin 2 [Homo sapiens (human)] - Gene - NCBI". Retrieved 8 April 2019.
  16. ^ Fukuyama K, Matsubara H, Tsukihara T, Katsube Y (November 1989). "Structure of [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus refined at 2.3 A resolution. Structural comparisons of bacterial ferredoxins". Journal of Molecular Biology. 210 (2): 383–98. doi:10.1016/0022-2836(89)90338-0. PMID 2600971.
  17. ^ Duée ED, Fanchon E, Vicat J, Sieker LC, Meyer J, Moulis JM (November 1994). "Refined crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici at 1.84 A resolution". Journal of Molecular Biology. 243 (4): 683–95. doi:10.1016/0022-2836(94)90041-8. PMID 7966291.

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2Fe-2S iron-sulfur cluster binding domain Provide feedback

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This tab holds annotation information from the InterPro database.

InterPro entry IPR001041

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 Ferredoxin family [ PUBMED:2065785 ]. 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-type domain have been determined [ PUBMED:8586613 ]. The domain is classified as a beta-grasp, which is characterised as having a beta-sheet comprised of four beta-strands and one alpha-helix flanking the sheet. The two Fe atoms are coordinated tetrahedrally by the two inorganic S atoms and four cysteinyl S atoms.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Fer2 (CL0486), which has the following description:

The 2Fe-2S ferredoxin family have a general core structure consisting of beta(2)-alpha-beta(2) which abeta-grasp type fold. The domani is around one hundred amino acids with four conserved cysteine residues to which the 2Fe-2S cluster is ligated.

The clan contains the following 5 members:

DHODB_Fe-S_bind Fer2 Fer2_2 Fer2_3 Fer2_4


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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: fer2;
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL
Number in seed: 206
Number in full: 46841
Average length of the domain: 75.20 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 22.39 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 78
Family (HMM) version: 30
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fer2 domain has been found. There are 435 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0X4G4 View 3D Structure Click here
A0A0R0G5H5 View 3D Structure Click here
A0A0R0GLS0 View 3D Structure Click here
A0A0R0JTR0 View 3D Structure Click here
A0A1D6EVV4 View 3D Structure Click here
A0A1D6FPD0 View 3D Structure Click here
A0A1D6GFT6 View 3D Structure Click here
A0A1D6HX68 View 3D Structure Click here
A0A1D6JN19 View 3D Structure Click here
A0A1D6K6B9 View 3D Structure Click here
A0A1D6L715 View 3D Structure Click here
A0A1D6L725 View 3D Structure Click here
A0A1D6L755 View 3D Structure Click here
A0A1D6M542 View 3D Structure Click here
A0A1D6MBZ6 View 3D Structure Click here
A0A1D6MF08 View 3D Structure Click here
A0A1D6NT01 View 3D Structure Click here
A0A1D6PRE2 View 3D Structure Click here
A0A1D8PJS2 View 3D Structure Click here
A0A2R8Q1T4 View 3D Structure Click here
A0A2R8QF75 View 3D Structure Click here
A0A368UHS1 View 3D Structure Click here
A0QTU9 View 3D Structure Click here
A0R525 View 3D Structure Click here
A2YQD9 View 3D Structure Click here
A3MYM7 View 3D Structure Click here
A4I234 View 3D Structure Click here
A4I755 View 3D Structure Click here
A4I756 View 3D Structure Click here
A4I757 View 3D Structure Click here
A4I758 View 3D Structure Click here
A6T526 View 3D Structure Click here
A6VLY1 View 3D Structure Click here
A7IPX7 View 3D Structure Click here
B1P758 View 3D Structure Click here
B1P759 View 3D Structure Click here
B4F9V1 View 3D Structure Click here
B4FVP6 View 3D Structure Click here
B4FYW4 View 3D Structure Click here
B6SP61 View 3D Structure Click here