mcr Resolved · high auto-curated
H37Rv Rv1143 · MTBC0 mtbc0_001228 ·
360 aa · 1278502–1279584 (+) ·
RefSeq NP_215659.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alpha-methylacyl-CoA racemase |
|---|---|
| MTBC0 PGAP re-annotation | alpha-methylacyl-CoA racemase |
| Revised (this work) | Alpha-methylacyl-CoA racemase. Pfam: CoA_transf_3 (PF02515.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06543
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Alpha-methylacyl-CoA racemase |
| EC (curated) |
EC 5.1.99.4
|
| Curated function | Catalyzes the epimerization of (2R)- and (2S)-methylacyl-coenzyme A (CoA) thioesters. Accepts as substrates a wide range of alpha-methylacyl-CoAs, including (2R)-2-methylmyristoyl-CoA and (2S)-2-methylmyristoyl-CoA, (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, and the cholesterol esters (25R)-3-oxo-cholest-4-en-26-oyl-CoA and (25S)-3-oxo-cholest-4-en-26-oyl-CoA. Can also catalyze the interconversion of the non-physiologic substrates (2R)-ibuprofenoyl-CoA and (2S)-ibuprofenoyl-CoA, which are potential competitive inhibitors of the enzyme. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | mcr |
| eggNOG description | carnitine dehydratase |
| Orthologous group | COG1804 |
| EC number |
EC 5.1.99.4
|
| KEGG orthology |
K01796
|
| KEGG pathways |
map00120, map01100, map04146
|
| KEGG modules |
M00104
|
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) pseudogene candidate
| pN/pS | 0.201 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 17.65% of strains (25629) · 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 |
|---|---|---|---|---|
CoA_transf_3 | PF02515.23 | 4.8e-81 | 5–343 | CoA-transferase family III |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1144 (oxidoreductase), high confidence from genomic context alone (score 906 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1144 |
oxidoreductase | 909 | 906 ctx | neighborhood:872 |
Rv0855 far |
fatty-acid-CoA racemase | 903 | 903 | database:900 |
Rv1142c echA10 |
enoyl-CoA hydratase EchA10 | 808 | 801 ctx | neighborhood:780 |
Rv3504 fadE26 |
acyl-CoA dehydrogenase FadE26 | 670 | 658 | database:631 |
Rv3505 fadE27 |
acyl-CoA dehydrogenase FadE27 | 669 | 657 | database:631 |
Rv3515c fadD19 |
acyl-CoA synthetase | 527 | 510 | database:500 |
Rv3389c htdY |
3-hydroxyacyl-thioester dehydratase HtdY | 518 | 499 | |
Rv0636 hadB |
(3R)-hydroxyacyl-ACP dehydratase subunit HadB | 514 | 496 | |
Rv1141c echA11 |
enoyl-CoA hydratase EchA11 | 510 | 491 ctx | neighborhood:434 |
Rv1043c hyp |
hypothetical protein | 486 | 486 | database:482 |
Rv3671c marP |
serine protease | 485 | 485 | database:482 |
Rv1934c fadE17 |
acyl-CoA dehydrogenase FadE17 | 502 | 484 | |
Rv1223 htrA |
serine protease HtrA | 484 | 484 | database:482 |
Rv0983 pepD |
serine protease PepD | 483 | 484 | database:482 |
Rv0125 pepA |
serine protease PepA | 483 | 484 | database:482 |
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: alpha-methylacyl-CoA racemase
- MTBC0 PGAP product: alpha-methylacyl-CoA racemase
- Pfam (hmmscan --cut_ga): CoA_transf_3 PF02515.23 (E=5e-81)
- (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_215659.1)
- Domains: Pfam-A via hmmscan --cut_ga — CoA_transf_3 (PF02515.23)
- 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
COG1804 - Curated reference: UniProt O06543 (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 —
37 functional partner(s); context anchor
Rv1144 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001228|Rv1143|mcr MAGPLSGLRVVELAGIGPGPHAAMILGDLGADVVRIDRPSSVDGISRDAMLRNRRIVTADLKSDQGLELALKLIAKADVLIEGYRPGVTERLGLGPEECAKVNDRLIYARMTGWGQTGPRSQQAGHDINYISLNGILHAIGRGDERPVPPLNLVGDFGGGSMFLLVGILAALWERQSSGKGQVVDAAMVDGSSVLIQMMWAMRATGMWTDTRGANMLDGGAPYYDTYECADGRYVAVGAIEPQFYAAMLAGLGLDAAELPPQNDRARWPELRALLTEAFASHDRDHWGAVFANSDACVTPVLAFGEVHNEPHIIERNTFYEANGGWQPMPAPRFSRTASSQPRPPAATIDIEAVLTDWDG