mutB Resolved · high auto-curated
H37Rv Rv1493 · MTBC0 mtbc0_001597 ·
750 aa · 1693810–1696062 (+) ·
RefSeq NP_216009.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | methylmalonyl-CoA mutase large subunit |
|---|---|
| MTBC0 PGAP re-annotation | methylmalonyl-CoA mutase |
| Revised (this work) | Methylmalonyl-CoA mutase. Pfam: MM_CoA_mutase (PF01642.29), B12-binding (PF02310.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJK5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable methylmalonyl-CoA mutase large subunit |
| EC (curated) |
EC 5.4.99.2
|
| Curated function | Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | mutB |
| eggNOG description | Methylmalonyl-CoA mutase |
| Orthologous group | COG2185 |
| EC number |
EC 5.4.99.2
|
| KEGG orthology |
K01847
|
| KEGG pathways |
map00280, map00630, map00640, map00720, map01100, map01120, map01200
|
| KEGG modules |
M00373, M00376, M00741
|
| Gene Ontology (25) |
GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0008150, GO:0008152, GO:0009987, GO:0016020, GO:0016999, GO:0017144 +13 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 | 0.126 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (239) · clonal |
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 |
|---|---|---|---|---|
MM_CoA_mutase | PF01642.29 | 2.9e-243 | 52–577 | Methylmalonyl-CoA mutase |
B12-binding | PF02310.25 | 2.8e-18 | 618–733 | B12 binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mutA (methylmalonyl-CoA mutase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1492 mutA |
methylmalonyl-CoA mutase small subunit | 999 | 1000 ctx | neighborhood:801 coexpression:784 experimental:999 database:900 |
Rv1496 meaB |
transport system kinase | 996 | 994 ctx | neighborhood:789 cooccurence:774 coexpression:857 textmining:432 |
Rv1322A hyp |
hypothetical protein | 996 | 978 ctx | cooccurence:758 database:900 textmining:854 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 941 | 923 | database:900 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 944 | 919 | database:900 |
Rv1489A hyp |
hypothetical protein | 875 | 863 | experimental:782 |
Rv2967c pca |
pyruvate carboxylase | 881 | 824 | database:800 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 847 | 820 | database:800 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 827 | 817 | database:800 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 948 | 812 | database:800 textmining:740 |
Rv1240 mdh |
malate dehydrogenase | 891 | 810 | database:800 textmining:450 |
Rv0889c citA |
citrate synthase 2 | 871 | 807 | database:800 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 864 | 807 | database:800 |
Rv0896 gltA2 |
citrate synthase 1 | 866 | 806 | database:800 |
Rv2852c mqo |
malate:quinone oxidoreductase | 806 | 806 | database:800 |
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: methylmalonyl-CoA mutase large subunit
- MTBC0 PGAP product: methylmalonyl-CoA mutase
- Pfam (hmmscan --cut_ga): MM_CoA_mutase PF01642.29 (E=3e-243), B12-binding PF02310.25 (E=3e-18)
- (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_216009.1)
- Domains: Pfam-A via hmmscan --cut_ga — MM_CoA_mutase (PF01642.29), B12-binding (PF02310.25)
- 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
COG2185 - Curated reference: UniProt P9WJK5 (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 —
64 functional partner(s); context anchor
mutA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001597|Rv1493|mutB MTTKTPVIGSFAGVPLHSERAAQSPTEAAVHTHVAAAAAAHGYTPEQLVWHTPEGIDVTPVYIAADRAAAEAEGYPLHSFPGEPPFVRGPYPTMYVNQPWTIRQYAGFSTAADSNAFYRRNLAAGQKGLSVAFDLATHRGYDSDHPRVQGDVGMAGVAIDSILDMRQLFDGIDLSTVSVSMTMNGAVLPILALYVVAAEEQGVAPEQLAGTIQNDILKEFMVRNTYIYPPKPSMRIISDIFAYTSAKMPKFNSISISGYHIQEAGATADLELAYTLADGVDYIRAGLNAGLDIDSFAPRLSFFWGIGMNFFMEVAKLRAGRLLWSELVAQFAPKSAKSLSLRTHSQTSGWSLTAQDVFNNVARTCIEAMAATQGHTQSLHTNALDEALALPTDFSARIARNTQLVLQQESGTTRPIDPWGGSYYVEWLTHRLARRARAHIAEVAEHGGMAQAISDGIPKLRIEEAAARTQARIDSGQQPVVGVNKYQVPEDHEIEVLKVENSRVRAEQLAKLQRLRAGRDEPAVRAALAELTRAAAEQGRAGADGLGNNLLALAIDAARAQATVGEISEALEKVYGRHRAEIRTISGVYRDEVGKAPNIAAATELVEKFAEADGRRPRILIAKMGQDGHDRGQKVIATAFADIGFDVDVGSLFSTPEEVARQAADNDVHVIGVSSLAAGHLTLVPALRDALAQVGRPDIMIVVGGVIPPGDFDELYAAGATAIFPPGTVIADAAIDLLHRLAERLGYTLD