Nsp7
- mutation effect predictions
Mutation predictions using the EVcouplings model (Hopf et al. 2017). Pairwise interaction terms capture how surrounding amino acids impact mutation effect.
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legend
Column: position in protein sequence. Row: amino acid substituted at position. x-labels show the wild-type SARS-CoV-2 amino acid followed by position (e.g. “A100”). Where SARS-CoV-2 is different than the SARS-CoV (2003) sequence, magenta x-labels include the SARS-CoV amino acid after the position (e.g. “A100K” for A in SARS-CoV-2 and K in SARS-CoV). Black “x”s show the SARS-CoV-2 amino acid at each position. Magenta “x”s show the SARS-CoV amino acid at each position, when different from SARS-CoV-2.
Black lines show regions excluded due to low alignment coverage, these may be insertions largely unique to SARS-CoV-2. Magenta lines show deletions relative to SARS-CoV.
Column: position in protein sequence. Row: amino acid substituted at position. x-labels show the wild-type SARS-CoV-2 amino acid followed by position (e.g. “A100”). Where SARS-CoV-2 is different than the SARS-CoV (2003) sequence, magenta x-labels include the SARS-CoV amino acid after the position (e.g. “A100K” for A in SARS-CoV-2 and K in SARS-CoV). Black “x”s show the SARS-CoV-2 amino acid at each position. Magenta “x”s show the SARS-CoV amino acid at each position, when different from SARS-CoV-2.
Black lines show regions excluded due to low alignment coverage, these may be insertions largely unique to SARS-CoV-2. Magenta lines show deletions relative to SARS-CoV.
Mutation predictions using a simple model with only sitewise terms, not context specific.
download table
legend
Column: position in protein sequence. Row: amino acid substituted at position. x-labels show the wild-type SARS-CoV-2 amino acid followed by position (e.g. “A100”). Where SARS-CoV-2 is different than the SARS-CoV (2003) sequence, magenta x-labels include the SARS-CoV amino acid after the position (e.g. “A100K” for A in SARS-CoV-2 and K in SARS-CoV). Black “x”s show the SARS-CoV-2 amino acid at each position. Magenta “x”s show the SARS-CoV amino acid at each position, when different from SARS-CoV-2.
Black lines show regions excluded due to low alignment coverage, these may be insertions largely unique to SARS-CoV-2. Magenta lines show deletions relative to SARS-CoV.
Column: position in protein sequence. Row: amino acid substituted at position. x-labels show the wild-type SARS-CoV-2 amino acid followed by position (e.g. “A100”). Where SARS-CoV-2 is different than the SARS-CoV (2003) sequence, magenta x-labels include the SARS-CoV amino acid after the position (e.g. “A100K” for A in SARS-CoV-2 and K in SARS-CoV). Black “x”s show the SARS-CoV-2 amino acid at each position. Magenta “x”s show the SARS-CoV amino acid at each position, when different from SARS-CoV-2.
Black lines show regions excluded due to low alignment coverage, these may be insertions largely unique to SARS-CoV-2. Magenta lines show deletions relative to SARS-CoV.
This is a visualization of the pairwise interactions learned by the EVcouplings model (Hopf et al. 2017) from the variation in our natural sequence alignment.
Gray dots show the pairs of residues that interact most strongly, each is sized according to the total magnitude of interaction. Mousing over a dot shows the matrix of interaction terms for pairs of amino acids at those two positions. Purple shows less fit interactions, yellow shows favorable interactions. The matrix shows only amino acids that appear in the alignment. The frequency of amino acids at each site is shown along the plot edges.
3D structures of this protein are not available or we have yet to compare against them.
How many sequences are aligned?
We aligned 3178 sequences (279 unique to the entire length of SARS-CoV-2 nsp7 (L=83aa, ncbi: YP_009725303, uniprot: R1AB_SARS2). 1440 sequences are from betacoronaviruses, 1041 alpha, 498 gamma, 127 delta, and 71 from unclassified coronavirinae.
Download or view the alignment.
Nsp7 sequence
>nsp7-YP_009725303/1-83
SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA
TLQ
We aligned this protein against the equivalent protein in SARS-CoV, reference genome NC_004718.
Mutations and insertions relative to the 2003 virus are listed below. Click here for amino acid differences to SARS-CoV in all proteins.
Mutations and insertions relative to the 2003 virus are listed below. Click here for amino acid differences to SARS-CoV in all proteins.
| aa | SARS | aa | CoV-2 | position | SARS | position | CoV-2 |
|---|---|---|---|
| R | K | 70 | 70 |
We aligned this protein against the equivalent protein in RatG13, reference genome MN996532.
Mutations and insertions relative to RatG13 are listed below. Click here for amino acid differences to RatG13 in all proteins.
Mutations and insertions relative to RatG13 are listed below. Click here for amino acid differences to RatG13 in all proteins.
| aa | RatG13 | aa | CoV-2 | position | RatG13 | position | CoV-2 |
|---|
*Predictions Limited by Available Coronavirus Sequences*
Available Nsp7 sequences have limited diversity. Of 3178 aligned sequences there are effectively 52 sequences less than 90% identical.
Still, there is noisy overlap between evolutionary couplings and 3D contacts in solved structures of Nsp7.
There are substantial differences between structures of Nsp7- with different regions captured in structure and different helix topology. Further sequencing of coronaviruses will improve coevolution predictions, and might reveal which interactions are most biologically meaningful.
Note: Nsp7 forms a complex with Nsp8 and Nsp12, we are in process of analyzing coevolution between the three proteins. This may teach us about quartenary structure of the virus's RNA-dependent RNA polymerase.