EFI - Enzyme Similarity Tool

This web resource is supported by a Research Resource from the National Institute of General Medical Sciences (R24GM141196-01).

The tools are available without charge or license to both academic and commercial users.

Important Notice

The UniProtKB database used by the EFI tools is undergoing major reorganization starting with the just-released version 2025_04 (https://www.uniprot.org/help/refprot_only_changes). When the reorganization is fully implemented (2026_02 release, Spring 2026), the number of proteins in UniProtKB will decrease from ~253M accessions in the previous 2025_03 release to ~141M accessions in the 2026_02 release.

In response to these changes, we will provide the previous 2025_03 release until the 2026_02 release is available.

The current 2025_04 release removed 82M UniProt IDs; the UniProt pages providing functional annotation for these IDs are no longer active. A new Metadata Tool provides access to the node attribute metadata for all UniProt IDs in the 2025_03 release that the tools continue to use during the UniProtKB reorganization. The Tool is available using the tab at the top of each page.

More information about the reorganization is located here.

EFI-EST and Cytoscape Tutorials

References

1.Using sequence similarity networks for visualization of relationships across diverse protein superfamilies. Atkinson HJ, Morris JH, Ferrin TE, Babbitt PC (2009) PLoS One 4, e4345.

2. Pythoscape: a framework for generation of large protein similarity networks. Barber AE 2nd, Babbitt PC (2012) Bioinformatics 28, 2845-6.

3. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Genome Res 13, 2498-504.

4. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Weizhong L, Godzik A (2006) Bioinformatics 22, 1658-9.

5. CD-HIT: accelerated for clustering the next generation sequencing data. Fu L, Niu B, Zhu Z, Wu S, Li W (2012) Bioinformatics 28, 3150-2.

6. Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks. Gerlt JA, Bouvier JT, Davidson DB, Imker HJ, Sadkhin B, Slater DR, Whalen KL. (2015) Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics doi:10.1016/j.bbapap.2015.04.015

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