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. 2014 Jan;42(Database issue):D222-30.
doi: 10.1093/nar/gkt1223. Epub 2013 Nov 27.

Pfam: the protein families database

Robert D Finn  1 , Alex Bateman, Jody Clements, Penelope Coggill, Ruth Y Eberhardt, Sean R Eddy, Andreas Heger, Kirstie Hetherington, Liisa Holm, Jaina Mistry, Erik L L Sonnhammer, John Tate, Marco Punta
Affiliations

Pfam: the protein families database

Robert D Finn et al. Nucleic Acids Res. 2014 Jan.

Abstract

Pfam, available via servers in the UK (http://pfam.sanger.ac.uk/) and the USA (http://pfam.janelia.org/), is a widely used database of protein families, containing 14 831 manually curated entries in the current release, version 27.0. Since the last update article 2 years ago, we have generated 1182 new families and maintained sequence coverage of the UniProt Knowledgebase (UniProtKB) at nearly 80%, despite a 50% increase in the size of the underlying sequence database. Since our 2012 article describing Pfam, we have also undertaken a comprehensive review of the features that are provided by Pfam over and above the basic family data. For each feature, we determined the relevance, computational burden, usage statistics and the functionality of the feature in a website context. As a consequence of this review, we have removed some features, enhanced others and developed new ones to meet the changing demands of computational biology. Here, we describe the changes to Pfam content. Notably, we now provide family alignments based on four different representative proteome sequence data sets and a new interactive DNA search interface. We also discuss the mapping between Pfam and known 3D structures.

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Figures

Figure 1.
Figure 1.
Table from the ‘Alignments’ tab of the family page for COX1 (PF00115), showing the availability of different views and different alignments for COX1. The posterior probability-based alignment is only available for the full alignments as it is derived from the alignment of a sequence to the HMM, as indicated by the subscript 1 in the corresponding seed alignment cell.
Figure 2.
Figure 2.
Results from searching Pfam with the Hepatitis B virus isolate G376-7, complete genome (GenBank accession AF384371.1), providing a striking example of overlapping genes. The six reading frames are displayed graphically in the top box of the results page. All three reading frames from the positive strand contain matches to Pfam-A, which are tabulated below. The positions of stop codons are indicated by the square lollipops. The results are shown with the ‘protein’ coordinates of the open reading frame, but it is also possible to toggle this to DNA sequence coordinates. This search tool accepts sequences up to 80 000 nucleotides in length, and searches the Pfam-A HMM library using the gathering threshold.
Figure 3.
Figure 3.
Graphical representation of the Pfam sequence annotations for human tyrosine-protein kinase ABL1 sequence (UniProtKB accession P00519). This sequence matches four different Pfam-A entries, SH3_1 (PF00018), SH2 (PF00017), Pkinase_Tyr (PF007714) and F_actin-bind (PF08919). Between the Pkinase_Tyr and F_actin_bind families is a long region of disorder, indicated by the presence of the grey boxes on the sequence. A disorder prediction does not necessarily mean that the sequence is not conserved, highlighted by the presence of an overlapping Pfam-B region (striped box).
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