Top Level Name

  ⌊ Superfamily (extended) Ferric Reductase Domain

Family known
Total 100% <100% Family unknown
Functional domains 282 0 19 263
UniProtKB 426 0 56 370
GI 959 0 107 852
Structures 1
Reactions 0
Functional domains of this superfamily were last updated on Dec. 16, 2016
New functional domains were last added to this superfamily on April 22, 2013

This superfamily is still undergoing annotation.

A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.

Membership appears to require all three of the InterPro domains: IPR013130, IPR017927, and IPR013121

Zhang X, Krause KH, Xenarios I, Soldati T, Boeckmann B

Evolution of the Ferric Reductase Domain (FRD) Superfamily: Modularity, Functional Diversification, and Signature Motifs

▸ Abstract

PLoS One 2013;8(3):None-None | PubMed ID: 23505460

Ferric Reductase Domain Superfamily Status: Dataset verified from reference paper (list from as supplementary material) (22/04/2013) Superfamily created - (22/04/2013) Sequences added to SF_52 (23/04/2013) Number of EFDs: 282 Still need to verify details with paper. Only very basic annotation done so far, General Notes: SF identified from primary literature: PMID:23505460 Not one of Raynee's original set.

Sequence Similarity Networks

Download a Sequence Similarity Network of this superfamily (XGMML format ).

Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given edge-score cutoff. The edge score is either a bit score for full networks or mean E values for a Repnet. Additionally, these networks contain several attributes with data from the SFLD.

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Multiple Sequence Alignment

View the alignment of a representative set of sequences of this superfamily using

Multiple Sequence Alignment

Align one or multiple sequences to the alignment of a representative set of sequences of this superfamily.
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Data Type All (#) Known (#) Unknown (#)
Full length FASTA (282) (19) (263)
Complete annotation (.tsv) (282) (19) (263)
Annotation suitable for Excel ® (.tsv) (282) (19) (263)
Clear form

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Cutoff Value
The least significant edge-score at which pairwise similarities are included in the network. A bit score for the full network, or a mean E value for the Repnet.
XGMML format
Open in Cytoscape via:
 →Network (multiple file types)
Download the annotation of all sequences as shown in the table below as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Full length FASTA
Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
Complete annotation
Download complete annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file has all data but cell size can exceed the maximum supported by spreadsheet programs (such as Microsoft Excel ®).
Spreadsheet ready annotation
Annotation of sequences sets of this superfamily in a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application. Cells which exceed the allowed spreadsheet maximum (32.5K) are preceded by the word "Truncated" and clipped short.
Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues
Depth of the multi-level Subgroup hierarchy.