Many of the proteins in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are cleavage products of the replicase polyprotein 1ab (uniprot:P0DTD1). Unfortunately, the bioinformatics community is not so comfortable with proteins like this and nomenclature remains tricky. Luckily, the Biological Expression Language (BEL) has exactly the right tool to encode information about these proteins using the fragment() function.

SARS-CoV-2 Genome

This image was modified from the C&EN article What do we know about the novel coronavirus’s 29 proteins?

UniProt lists each of the 16 non-structural proteins (often written as symbols nsp1-nsp16) as protein chains of the main protein entry, uniprot:P0DTD1. These chains are assigned identifiers following the regular expression pattern of PRO_\d{10}. The Identifiers.org registered this pattern under the prefix uniprot.chain. While it resolves to URLs following the pattern of https://www.uniprot.org/uniprot/<uniprot_id>#<chain_id>, it appears that the parent protein’s UniProt identifier is looked up automatically . This is really good news and means that we can start using stable CURIEs to identify these proteins, even if like me, you’ve never used this prefix before.

Alternatively, BEL allows you to write out the relationship between the parent protein and the fragment using the fragment() / frag() function (docs). For example, the nsp1 fragment from position 1-180 can be written in BEL either as p(uniprot.chain:PRO_0000449619) or as a fragment p(uniprot:P0DTD1 ! R1AB_SARS2, frag(1_180)). The entire table of non-structural proteins is written out below for your copy/paste convenience in BEL coding.

Symbol Chain Positions Name BEL
nsp1 PRO_0000449619 1 – 180 Host translation inhibitor nsp1 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(1_180))
nsp2 PRO_0000449620 181 – 818 Non-structural protein 2 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(181_818))
nsp3 PRO_0000449621 819 – 2763 Non-structural protein 3 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(819_2763))
nsp4 PRO_0000449622 2764 – 3263 Non-structural protein 4 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(2764_3263))
nsp5 PRO_0000449623 3264 – 3569 3C-like proteinase p(uniprot:P0DTD1 ! R1AB_SARS2, frag(3264_3569))
nsp6 PRO_0000449624 3570 – 3859 Non-structural protein 6 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(3570_3859))
nsp7 PRO_0000449625 3860 – 3942 Non-structural protein 7 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(3860_3942))
nsp8 PRO_0000449626 3943 – 4140 Non-structural protein 8 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(3943_4140))
nsp9 PRO_0000449627 4141 – 4253 Non-structural protein 9 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(4141_4253))
nsp10 PRO_0000449628 4254 – 4392 Non-structural protein 10 p(uniprot:P0DTD1 ! R1AB_SARS2, frag(4254_4392))
nsp12 PRO_0000449629 4393 – 5324 RNA-directed RNA polymerase p(uniprot:P0DTD1 ! R1AB_SARS2, frag(4393_5324))
nsp13 PRO_0000449630 5325 – 5925 Helicase p(uniprot:P0DTD1 ! R1AB_SARS2, frag(5325_5925))
nsp14 PRO_0000449631 5926 – 6452 Proofreading exoribonuclease p(uniprot:P0DTD1 ! R1AB_SARS2, frag(5926_6452))
nsp15 PRO_0000449632 6453 – 6798 Uridylate-specific endoribonuclease p(uniprot:P0DTD1 ! R1AB_SARS2, frag(6453_6798))
nsp16 PRO_0000449633 6799 – 7096 2’-O-methyltransferase p(uniprot:P0DTD1 ! R1AB_SARS2, frag(6799_7096))

I’m not sure what happened to #11. UniProt isn’t listing it here. There’s also the Replicase polyprotein 1a, which lists nsp1-nsp11, but I’m not sure what the difference is yet.

When I first started writing this, I wasn’t actually aware of the existence of the uniprot.chain entry in Identifiers.org. This makes things a lot better! However, this leaves two tasks for me:

  1. Integrate the uniprot.chain nomenclature into PyOBO such that identifiers can be validated and easily resolved to names

  2. Generate equivalence relationships in BEL linking the CURIE-named and ontologically-defined versions of each as in:

     p(uniprot.chain:PRO_0000449619) equivalentTo p(uniprot:P0DTD1 ! R1AB_SARS2, frag(1_180))
 ...
 p(uniprot.chain:PRO_0000449633) equivalentTo p(uniprot:P0DTD1 ! R1AB_SARS2, frag(6799_7096))

Happy BEL coding!