mbtA Resolved · high auto-curated
H37Rv Rv2384 · MTBC0 mtbc0_002536 ·
565 aa · 2700129–2701826 (+) ·
RefSeq NP_216900.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2,3-dihydroxybenzoate-AMP ligase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional salicyl-AMP ligase/salicyl-S-ArCP synthetase MbtA |
| Revised (this work) | Bifunctional salicyl-AMP ligase/salicyl-S-ArCP synthetase MbtA. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71716
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Salicyl-AMP ligase / salicyl-S-ArCP synthetase |
| EC (curated) |
EC 2.7.7.-, EC 6.2.1.-
|
| Curated function | Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP-dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtA |
| eggNOG description | AMP-dependent synthetase and ligase |
| Orthologous group | COG1021 |
| EC number |
EC 2.7.7.58, EC 6.3.2.14
|
| KEGG orthology |
K02363, K04787
|
| KEGG pathways |
map01053, map01110, map01130
|
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 | 0.922 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 | 1.8e-76 | 48–416 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 5.3e-10 | 468–542 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtB (phenyloxazoline synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2383c mbtB |
phenyloxazoline synthase | 999 | 1000 ctx | neighborhood:784 coexpression:999 experimental:699 textmining:761 |
Rv2386c mbtI |
salicylate synthase | 998 | 971 ctx | fusion:838 coexpression:810 textmining:946 |
Rv3800c pks13 |
polyketide synthase | 969 | 940 | coexpression:917 textmining:512 |
Rv2377c mbtH hyp |
hypothetical protein | 980 | 931 ctx | neighborhood:450 cooccurence:492 coexpression:774 textmining:724 |
Rv3215 entC |
isochorismate synthase | 947 | 926 ctx | cooccurence:404 coexpression:854 |
Rv2385 mbtJ |
acetyl hydrolase | 990 | 912 ctx | neighborhood:582 coexpression:798 textmining:898 |
Rv1348 irtA |
iron ABC transporter ATP-binding protein/permease IrtA | 956 | 896 | coexpression:853 textmining:596 |
Rv2380c mbtE |
peptide synthetase | 933 | 876 ctx | neighborhood:433 coexpression:718 textmining:483 |
Rv2379c mbtF |
peptide synthetase | 918 | 874 | coexpression:685 |
Rv2382c mbtC |
polyketide synthetase | 982 | 854 ctx | neighborhood:771 textmining:883 |
Rv3839 hyp |
hypothetical protein | 864 | 827 | coexpression:827 |
Rv1349 irtB |
iron ABC transporter ATP-binding protein/permease IrtB | 916 | 825 | coexpression:777 textmining:541 |
Rv2123 PPE37 |
PPE family protein PPE37 | 826 | 806 | coexpression:806 |
Rv3402c hyp |
hypothetical protein | 869 | 779 | coexpression:778 textmining:436 |
Rv0101 nrp |
peptide synthetase Nrp | 800 | 775 | coexpression:654 |
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: 2,3-dihydroxybenzoate-AMP ligase
- MTBC0 PGAP product: bifunctional salicyl-AMP ligase/salicyl-S-ArCP synthetase MbtA
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=2e-76), AMP-binding_C PF13193.13 (E=5e-10)
- (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_216900.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13)
- 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
COG1021 - Curated reference: UniProt P71716 (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 —
50 functional partner(s); context anchor
mbtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002536|Rv2384|mbtA MPPKAADGRRPSPDGGLGGFVPFPADRAASYRAAGYWSGRTLDTVLSDAARRWPDRLAVADAGDRPGHGGLSYAELDQRADRAAAALHGLGITPGDRVLLQLPNGCQFAVALFALLRAGAIPVMCLPGHRAAELGHFAAVSAATGLVVADVASGFDYRPMARELVADHPTLRHVIVDGDPGPFVSWAQLCAQAGTGSPAPPADPGSPALLLVSGGTTGMPKLIPRTHDDYVFNATASAALCRLSADDVYLVVLAAGHNFPLACPGLLGAMTVGATAVFAPDPSPEAAFAAIERHGVTVTALVPALAKLWAQSCEWEPVTPKSLRLLQVGGSKLEPEDARRVRTALTPGLQQVFGMAEGLLNFTRIGDPPEVVEHTQGRPLCPADELRIVNADGEPVGPGEEGELLVRGPYTLNGYFAAERDNERCFDPDGFYRSGDLVRRRDDGNLVVTGRVKDVICRAGETIAASDLEEQLLSHPAIFSAAAVGLPDQYLGEKICAAVVFAGAPITLAELNGYLDRRGVAAHTRPDQLVAMPALPTTPIGKIDKRAIVRQLGIATGPVTTQRCH