mbtM Resolved · high auto-curated
H37Rv Rv1345 · MTBC0 mtbc0_001442 ·
521 aa · 1519983–1521548 (+) ·
RefSeq NP_215861.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long-chain-fatty-acid--ACP ligase MbtM |
|---|---|
| MTBC0 PGAP re-annotation | long-chain-fatty acid--ACP ligase MbtM |
| Revised (this work) | Long-chain-fatty acid--ACP ligase MbtM. Pfam: AMP-binding (PF00501.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ41
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Medium/long-chain-fatty-acid--[acyl-carrier-protein] ligase MbtM |
| EC (curated) |
EC 6.2.1.20, EC 6.2.1.47
|
| Curated function | Activates lipidic moieties required for mycobactin biosynthesis. Converts medium- to long-chain aliphatic fatty acids into acyl adenylate, which is further transferred on to the phosphopantetheine arm of the carrier protein MbtL..; FUNCTION: May play a role in virulence by supporting bacterial growth in the liver. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtM |
| eggNOG description | Converts medium- to long-chain aliphatic fatty acids into acyl adenylate |
| Orthologous group | COG0318 |
| EC number |
EC 6.2.1.20
|
| KEGG orthology |
K00666, K01909
|
| KEGG pathways |
map00071
|
| Gene Ontology (65) |
GO:0000166, GO:0003674, GO:0003824, GO:0005488, GO:0005524, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633 +53 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 | 1.104 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 9 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 |
|---|---|---|---|---|
AMP-binding | PF00501.35 | 1.1e-36 | 29–384 | AMP-binding enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtN (acyl-[acyl-carrier-protein), high confidence from genomic context alone (score 982 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1346 mbtN |
acyl-[acyl-carrier-protein | 990 | 982 ctx | neighborhood:882 coexpression:817 textmining:484 |
Rv1344 mbtL |
acyl carrier protein MbtL | 964 | 928 ctx | neighborhood:882 textmining:532 |
Rv2380c mbtE |
peptide synthetase | 877 | 872 ctx | cooccurence:603 experimental:465 |
Rv2383c mbtB |
phenyloxazoline synthase | 863 | 786 ctx | cooccurence:560 |
Rv2379c mbtF |
peptide synthetase | 812 | 756 ctx | cooccurence:547 |
Rv0719 rplF |
50S ribosomal protein L6 | 696 | 696 | experimental:402 database:510 |
Rv2048c pks12 |
polyketide synthase | 708 | 684 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 757 | 682 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 706 | 681 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 706 | 681 | |
Rv1527c pks5 |
polyketide synthase | 704 | 679 | |
Rv3800c pks13 |
polyketide synthase | 679 | 638 | |
Rv2946c pks1 |
polyketide synthase | 667 | 635 | |
Rv0214 fadD4 |
fatty-acid--CoA ligase FadD4 | 631 | 631 ctx | cooccurence:631 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 633 | 612 |
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: long-chain-fatty-acid--ACP ligase MbtM
- MTBC0 PGAP product: long-chain-fatty acid--ACP ligase MbtM
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=1e-36)
- (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_215861.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35)
- 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
COG0318 - Curated reference: UniProt P9WQ41 (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 —
84 functional partner(s); context anchor
mbtN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001442|Rv1345|mbtM MSELAAVLTRSMQASAGDLMVLDRETSLWCRHPWPEVHGLAESVAAWLLDHDRPAAVGLVGEPTVELVAAIQGAWLAGAAVSILPGPVRGANDQRWADATLTRFLGIGVRTVLSQGSYLARLRSVDTAGVTIGDLSTAAHTNRSATPVASEGPAVLQGTAGSTGAPRTAILSPGAVLSNLRGLNQRVGTDAATDVGCSWLPLYHDMGLAFVLSAALAGAPLWLAPTTAFTASPFRWLSWLSDSGATMTAAPNFAYNLIGKYARRVSEVDLGALRVTLNGGEPVDCDGLTRFAEAMAPFGFDAGAVLPSYGLAESTCAVTVPVPGIGLLADRVIDGSGAHKHAVLGNPIPGMEVRISCGDQAAGNASREIGEIEIRGASMMAGYLGQQPIDPDDWFATGDLGYLGAGGLVVCGRAKEVISIAGRNIFPTEVELVAAQVRGVREGAVVALGTGDRSTRPGLVVAAEFRGPDEANARAELIQRVASECGIVPSDVVFVSPGSLPRTSSGKLRRLAVRRSLEMAD