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11  structures 2682  species 0  interactions 4422  sequences 161  architectures

Family: FeS (PF04060)

Summary: Putative Fe-S cluster

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Putative Fe-S cluster Provide feedback

This family includes a domain with four conserved cysteines that probably form an Fe-S redox cluster.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007202

The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is functional in the acetyl-CoA pathway of autotrophic carbon fixation in various bacteria and acrchaea, where it is essential for the biosynthesis of acetyl- CoA. CoFeSP acts in two methylation reactions: the transfer of a methyl group from methyltransferase (MeTr)-bound methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site cluster A of acetyl-CoA synthase (ACS). CoFeSP is a heterodimer consisting of a large subunit (CfsA) and a small subunit (CfsB). The large subunit has three domains: an amino (N)-terminal 4Fe-4S domain, a TIM barrel domain and a carboxy (C)-terminal domain that binds CoBeta-aqua-(5,6-dimethylbenzimiddazolylcobamide) (corrinoid). Methylation of CoFeSP only occurs in the low potential Co(I) state, which can be sporadically oxidized to the inactive Co(II) state, making its reductive reactivation necessary. The low-potential [4Fe-4S]2(+)/1(+) cluster is involved in the reductive reactivation of CoFeSP and is able to transfer electrons to cob(II)amide from NiFe-containing carbon monoxyde dehydrogenase (CODH), pyruvate:ferredoxin oxydoreductase or reduced ferredoxins [ PUBMED:16983091 , PUBMED:21640123 , PUBMED:22419154 ].

The 4Fe-4S domain lacks homology to the 4Fe-4S ferredoxin-type iron-sulfur binding domain, but is also found in bacterial electron transport complex protein RnfB [ PUBMED:21640123 ].

The 4Fe-4S domain consists of four helices (three alpha-helices from H1-H3 and one 3(10)-helix with the order alphaH1-alphaH2-3(10)H-alphaH3). This four-helix-bundle-like architecture positions the four cysteinyl ligands of the [4Fe-4S] cluster. The iron-sulfur cluster binding motif Cys-X(2)-Cys-X(4)-Cys-X(16)-Cys is located at loops connecting alphaH1 and alphaH2, connecting 3(10)H and alphaH3, and at the end of alphaH2. The [4Fe-4S] cluster is placed near the surface of the 4Fe-4S domain, but is shielded from the solvent by hydrophobic amino acids [ PUBMED:21640123 , PUBMED:22419154 ].

This entry represents the 4Fe-4S domain.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 4Fe-4S (CL0344), which has the following description:

Superfamily includes proteins containing domains which bind to iron-sulfur clusters. Members include bacterial ferredoxins, various dehydrogenases and various reductases. The structure of the domain is an alpha-antiparallel beta sandwich.

The clan contains the following 29 members:

ETF_QO Fer4 Fer4_10 Fer4_11 Fer4_12 Fer4_13 Fer4_14 Fer4_15 Fer4_16 Fer4_17 Fer4_18 Fer4_19 Fer4_2 Fer4_20 Fer4_21 Fer4_22 Fer4_23 Fer4_24 Fer4_3 Fer4_4 Fer4_5 Fer4_6 Fer4_7 Fer4_8 Fer4_9 FeS Molybdop_Fe4S4 Nitr_red_alph_N RLI


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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Representative proteomes UniProt

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 353
Number in full: 4422
Average length of the domain: 32.70 aa
Average identity of full alignment: 44 %
Average coverage of the sequence by the domain: 10.21 %

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 23.0 23.0
Trusted cut-off 23.0 23.0
Noise cut-off 22.9 22.9
Model length: 33
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Colour assignments

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


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 FeS domain has been found. There are 11 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
A0KLJ3 View 3D Structure Click here
A0L5G7 View 3D Structure Click here
A1K5F2 View 3D Structure Click here
A1S6N0 View 3D Structure Click here
A3QEN5 View 3D Structure Click here
A4VIV5 View 3D Structure Click here
A4XS52 View 3D Structure Click here
A8AH09 View 3D Structure Click here
A8H537 View 3D Structure Click here
A9MRW7 View 3D Structure Click here
B2VEQ2 View 3D Structure Click here
B7VLT8 View 3D Structure Click here
C4LEP6 View 3D Structure Click here
C5BDE6 View 3D Structure Click here
D5ARZ0 View 3D Structure Click here
H6LC27 View 3D Structure Click here
O27748 View 3D Structure Click here
O29871 View 3D Structure Click here
P57214 View 3D Structure Click here
P58323 View 3D Structure Click here
P71396 View 3D Structure Click here
P77223 View 3D Structure Click here
Q0AAG8 View 3D Structure Click here
Q0VP40 View 3D Structure Click here
Q2SKU5 View 3D Structure Click here
Q32FE5 View 3D Structure Click here
Q3IXC5 View 3D Structure Click here
Q3SHB7 View 3D Structure Click here
Q57576 View 3D Structure Click here
Q57583 View 3D Structure Click here
Q58720 View 3D Structure Click here
Q5E6B7 View 3D Structure Click here
Q5P1B1 View 3D Structure Click here
Q6D4W3 View 3D Structure Click here
Q7MM82 View 3D Structure Click here
Q7VNT5 View 3D Structure Click here
Q83KY6 View 3D Structure Click here
Q87MX3 View 3D Structure Click here
Q89AW9 View 3D Structure Click here
Q8EE80 View 3D Structure Click here