msrA Resolved · high auto-curated
H37Rv Rv0137c · MTBC0 mtbc0_000148 ·
182 aa · 165058–165606 (-) ·
RefSeq NP_214651.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | peptide methionine sulfoxide reductase MsrA |
|---|---|
| MTBC0 PGAP re-annotation | peptide-methionine (S)-S-oxide reductase MsrA |
| Revised (this work) | Peptide-methionine (S)-S-oxide reductase MsrA. Pfam: PMSR (PF01625.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJM5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptide methionine sulfoxide reductase MsrA |
| EC (curated) |
EC 1.8.4.11
|
| Curated function | Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | msrA |
| eggNOG description | Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine |
| Orthologous group | COG0225 |
| EC number |
EC 1.8.4.11, EC 1.8.4.12
|
| KEGG orthology |
K07304, K12267
|
| Gene Ontology (47) |
GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006950, GO:0006979, GO:0008113, GO:0008150, GO:0008152 +35 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.637 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PMSR | PF01625.29 | 1.6e-57 | 5–157 | Peptide methionine sulfoxide reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: msrB (peptide methionine sulfoxide reductase MsrB), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2674 msrB |
peptide methionine sulfoxide reductase MsrB | 999 | 993 ctx | fusion:900 cooccurence:749 coexpression:656 textmining:885 |
Rv2874 dipZ |
integral membrane C-type cytochrome biogenesis protein DipZ | 884 | 839 | experimental:562 database:596 |
Rv0816c thiX |
thioredoxin ThiX | 833 | 823 | experimental:562 database:596 |
Rv2878c mpt53 |
soluble secreted antigen Mpt53 | 832 | 822 | experimental:562 database:596 |
Rv0526 |
thioredoxin | 832 | 821 | experimental:562 database:596 |
Rv3673c |
membrane-anchored thioredoxin-like protein | 832 | 821 | experimental:562 database:596 |
Rv1677 dsbF |
lipoprotein DsbF | 832 | 821 | experimental:562 database:596 |
Rv0139 |
oxidoreductase | 818 | 811 ctx | neighborhood:786 |
Rv1629 polA |
DNA polymerase I | 877 | 794 | coexpression:787 textmining:429 |
Rv0138 hyp |
hypothetical protein | 780 | 780 ctx | neighborhood:779 |
Rv0140 hyp |
hypothetical protein | 584 | 583 ctx | neighborhood:582 |
Rv3198A |
glutaredoxin protein | 904 | 525 | experimental:484 textmining:807 |
Rv3053c nrdH |
glutaredoxin electron transport protein NrdH | 578 | 513 | experimental:484 |
Rv0508 hyp |
hypothetical protein | 558 | 512 | experimental:484 |
Rv0946c pgi |
glucose-6-phosphate isomerase | 456 | 429 | coexpression:409 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: peptide methionine sulfoxide reductase MsrA
- MTBC0 PGAP product: peptide-methionine (S)-S-oxide reductase MsrA
- Pfam (hmmscan --cut_ga): PMSR PF01625.29 (E=2e-57)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_214651.1)
- Domains: Pfam-A via hmmscan --cut_ga — PMSR (PF01625.29)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0225 - Curated reference: UniProt P9WJM5 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
29 functional partner(s); context anchor
msrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000148|Rv0137c|msrA MTSNQKAILAGGCFWGLQDLIRNQPGVVSTRVGYSGGNIPNATYRNHGTHAEAVEIIFDPTVTDYRTLLEFFFQIHDPTTKDRQGNDRGTSYRSAIFYFDEQQKRIALDTIADVEASGLWPGKVVTEVSPAGDFWEAEPEHQDYLQRYPNGYTCHFVRPGWRLPRRTAESALRASLSPELGT