etgB Resolved · high auto-curated
H37Rv Rv3703c · MTBC0 mtbc0_003925 ·
425 aa · 4169562–4170839 (-) ·
RefSeq NP_218220.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron(II)-dependent oxidoreductase EgtB |
|---|---|
| MTBC0 PGAP re-annotation | ergothioneine biosynthesis protein EgtB |
| Revised (this work) | Ergothioneine biosynthesis protein EgtB. Pfam: DinB_2 (PF12867.13), FGE-sulfatase (PF03781.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69671
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hercynine oxygenase |
| EC (curated) |
EC 1.14.99.50
|
| Curated function | Catalyzes the oxidative sulfurization of hercynine (N-alpha,N-alpha,N-alpha-trimethyl-L-histidine) into hercynyl-gamma-L-glutamyl-L-cysteine sulfoxide, a step in the biosynthesis pathway of ergothioneine. Ergothioneine is an antioxidant that protects mycobacteria from oxidative stress. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | egtB |
| eggNOG description | Catalyzes the oxidative sulfurization of hercynine (N- alpha,N-alpha,N-alpha-trimethyl-L-histidine) into hercynyl-gamma- L-glutamyl-L-cysteine sulfoxide, a step in the biosynthesis pathway of ergothioneine |
| Orthologous group | COG1262 |
| EC number |
EC 1.14.99.50
|
| KEGG orthology |
K18912
|
| KEGG pathways |
map00340
|
| Gene Ontology (70) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0005488, GO:0005506, GO:0006082, GO:0006520, GO:0006547, GO:0006548, GO:0006575, GO:0006577 +58 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 | 0.425 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
DinB_2 | PF12867.13 | 5.4e-11 | 11–137 | DinB superfamily |
FGE-sulfatase | PF03781.23 | 1.4e-67 | 166–423 | Sulfatase-modifying factor enzyme 1-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: egtD (histidine-specific methyltransferase EtgD), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3701c egtD |
histidine-specific methyltransferase EtgD | 999 | 1000 ctx | neighborhood:881 fusion:893 cooccurence:773 coexpression:811 database:900 textmining:745 |
Rv3702c egtC |
amidohydrolase EgtC | 999 | 999 ctx | neighborhood:881 cooccurence:681 coexpression:860 database:900 textmining:412 |
Rv3704c gshA |
glutamate--cysteine ligase | 997 | 992 ctx | neighborhood:881 cooccurence:410 coexpression:797 database:500 textmining:745 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 968 | 882 ctx | neighborhood:839 textmining:745 |
Rv3705c hyp |
hypothetical protein | 557 | 557 ctx | neighborhood:543 |
Rv0433 |
carboxylate-amine ligase | 513 | 513 | database:500 |
Rv3299c atsB |
arylsulfatase AtsB | 465 | 465 | experimental:430 |
Rv0663 atsD |
arylsulfatase AtsD | 451 | 452 | experimental:430 |
Rv3077 |
hydrolase | 451 | 451 | experimental:430 |
Rv0711 atsA |
arylsulfatase AtsA | 450 | 450 | experimental:430 |
Rv0296c |
sulfatase | 448 | 448 | experimental:430 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 450 | 424 | coexpression:405 |
Rv1464 csd |
cysteine desulfurase | 604 | 253 | textmining:492 |
Rv3778c |
aminotransferase | 422 | 185 | |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 967 | 90 | textmining:965 |
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: iron(II)-dependent oxidoreductase EgtB
- MTBC0 PGAP product: ergothioneine biosynthesis protein EgtB
- Pfam (hmmscan --cut_ga): DinB_2 PF12867.13 (E=5e-11), FGE-sulfatase PF03781.23 (E=1e-67)
- (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_218220.1)
- Domains: Pfam-A via hmmscan --cut_ga — DinB_2 (PF12867.13), FGE-sulfatase (PF03781.23)
- 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
COG1262 - Curated reference: UniProt O69671 (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 —
25 functional partner(s); context anchor
egtD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003925|Rv3703c|etgB MTSPEQLACHLARARARTLRLVDFDDAELCCQYDPLMSPLVWDLAHIGQQEELWLLRGGDPGQPGLLPPAVEGLYDAFEHSRASRVELPLLSPARARSYCATVRSAALDALAALPEDGDSFVFAMVISHENQHDETMLQALNLRTGSPLLAATSALPAGRPRMAGTSVLVAGGPFVLGVDAADEPCSLDNERPAHVVDVPAFRIGRVPVTNGEWQDFIDDGGYTQSRWWSERGWQHRQRAGLTAPQFWRSGGRTRTRFGHVEDIPADEPVQHVSYFEAEAYAAWAGARLPTEVEWEKACAWDPATGSRRRYPWGTEEPTDTYANLGGQTLRPAPVGAYPAGASACGAEQMLGDVWEWTTSPLRPWPGFVPMVYERYSQPFFGGDYRVLRGGSWAVEPAILRPSFRNWDHPYRRQIFAGVRLAWDI