Pfam 35.0 is released

November 19, 2021

Pfam 35.0 contains a total of 19,632 families and clans. Since the last release, we have built 460 new families, killed 7 families and created 12 new clans. UniProt Reference Proteomes has increased by 7% since Pfam 34.0, and now contains 61 million sequences. Of the sequences that are in UniProt Reference Proteomes, 75.2% have at least one Pfam match, and 48.7% of all residues fall within a Pfam family.

Sources of new families

In an effort to increase the Pfam coverage of metagenomic sequence space, we have created 250 metagenomic protein families. These families were built by clustering protein sequences from the MGnify and UniProt databases, aligning the sequences in each cluster, and using the resulting alignments to create new SEED alignments. We then used our usual building process to create new families from the SEED alignments.

We have also created 52 new families based on clusters from a new resource called DPCfam based on Density Peak Clustering, created by Allesandro Laio, Marco Punta and Elena Tea Russo. An interesting example of these families is the N-terminal domain of the Crinkler effector protein (PF20147). Crinkling- and necrosis-inducing proteins (CRNs) or Crinkler, are ubiquitously present and first described in plant pathogenic oomycetes, and have been shown to participate in processes controlling plant cell death and immunity. However, Crinkler is also found outside oomycetes, such as in the Rhizophagus irregularis crinkler effector protein 1 (RiCRN1) which, like other CRNs, functions in the plant nucleus, but plays an essential role in symbiosis progression and the proper initiation of arbuscule development. This suggests that Crinkler proteins are more ubiquitously distributed than first predicted, and that their function is not limited to plant death (PMID:30233541). The Pfam domain contains the conserved motif FLAK, and, from structure predictions, adopts the ubiquitin-like fold, as seen in the image below. 

Figure 1: N-terminal domain of RiCRN. The image was generated using an AlphaFold colab notebook and is displayed using Molstar.

We continue to be provided with new families from the group of L. Aravind from NCBI, and have added 42 of them to this release of Pfam. Many of these families represent novel domains and proteins found in phage defence systems of bacteria.

Pfam-N

We are really excited about the Pfam-N matches for Pfam 35.0, but there is still a bit of work to do before we can release them. In particular, we’re working on neural networks that can predict the location of the domains themselves, instead of relying on HMMER to do so, as with the previous Pfam-N release. It will take a little more time to ensure the quality of these annotations, and we will make another announcement when they are ready.

Enjoy Pfam 35.0!

Posted by the Pfam team

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