mbtH Resolved · high auto-curated
H37Rv Rv2377c · MTBC0 mtbc0_002529 ·
71 aa · 2680408–2680623 (-) ·
RefSeq NP_216893.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | mycobactin NRPS accessory protein MbtH |
| Revised (this work) | Mycobactin NRPS accessory protein MbtH. Pfam: MbtH (PF03621.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIP5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein MbtH |
| Curated function | Could be involved in mycobactin synthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mbtH |
| eggNOG description | protein conserved in bacteria |
| Orthologous group | COG3251 |
| KEGG orthology |
K05375, K16227
|
| KEGG pathways |
map00261, map01130
|
| KEGG modules |
M00736
|
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 | 0.278 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
MbtH | PF03621.19 | 1.2e-29 | 3–53 | MbtH-like protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks13 (polyketide synthase), high confidence from genomic context alone (score 1000 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 999 | 1000 ctx | neighborhood:400 coexpression:915 experimental:999 textmining:496 |
Rv2380c mbtE |
peptide synthetase | 999 | 1000 ctx | neighborhood:799 cooccurence:754 coexpression:887 experimental:972 textmining:835 |
Rv2383c mbtB |
phenyloxazoline synthase | 999 | 999 ctx | neighborhood:756 cooccurence:650 coexpression:971 experimental:564 textmining:864 |
Rv2379c mbtF |
peptide synthetase | 999 | 997 ctx | neighborhood:834 cooccurence:763 coexpression:867 experimental:564 textmining:847 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 996 | 990 ctx | neighborhood:882 coexpression:915 textmining:701 |
Rv0101 nrp |
peptide synthetase Nrp | 955 | 942 ctx | cooccurence:753 coexpression:431 experimental:564 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 980 | 931 ctx | neighborhood:450 cooccurence:492 coexpression:774 textmining:724 |
Rv3824c papA1 |
acyltransferase | 762 | 747 | coexpression:426 experimental:564 |
Rv1182 papA3 |
acyltransferase papA3 | 761 | 747 | coexpression:424 experimental:564 |
Rv3820c papA2 |
trehalose-2-sulfate acyltransferase | 760 | 746 | coexpression:422 experimental:564 |
Rv2928 tesA |
thioesterase TesA | 754 | 719 ctx | cooccurence:598 |
Rv2382c mbtC |
polyketide synthetase | 926 | 699 ctx | neighborhood:614 textmining:765 |
Rv1528c papA4 |
polyketide synthase associated protein PapA | 710 | 692 | coexpression:419 experimental:475 |
Rv1125 hyp |
hypothetical protein | 710 | 692 | coexpression:419 experimental:475 |
Rv2381c mbtD |
polyketide synthetase | 864 | 606 ctx | neighborhood:502 textmining:669 |
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: hypothetical protein
- MTBC0 PGAP product: mycobactin NRPS accessory protein MbtH
- Pfam (hmmscan --cut_ga): MbtH PF03621.19 (E=1e-29)
- (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_216893.1)
- Domains: Pfam-A via hmmscan --cut_ga — MbtH (PF03621.19)
- 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
COG3251 - Curated reference: UniProt P9WIP5 (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 —
40 functional partner(s); context anchor
pks13 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002529|Rv2377c|mbtH MSTNPFDDDNGAFFVLVNDEDQHSLWPVFADIPAGWRVVHGEASRAACLDYVEKNWTDLRPKSLRDAMAED