egtD Resolved · high auto-curated
H37Rv Rv3701c · MTBC0 mtbc0_003923 ·
321 aa · 4167899–4168864 (-) ·
RefSeq NP_218218.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | histidine-specific methyltransferase EtgD |
|---|---|
| MTBC0 PGAP re-annotation | L-histidine N(alpha)-methyltransferase |
| Revised (this work) | L-histidine N(alpha)-methyltransferase. Pfam: Methyltransf_33 (PF10017.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN47
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Histidine N-alpha-methyltransferase |
| EC (curated) |
EC 2.1.1.44
|
| Curated function | Catalyzes the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | egtD |
| eggNOG description | Catalyzes the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine |
| Orthologous group | COG4301 |
| EC number |
EC 2.1.1.44
|
| KEGG orthology |
K18911
|
| KEGG pathways |
map00340
|
| Gene Ontology (86) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006464, GO:0006479, GO:0006520, GO:0006547 +74 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 | 0.137 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (215) · 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 |
|---|---|---|---|---|
Methyltransf_33 | PF10017.16 | 6.0e-114 | 19–320 | Histidine-specific methyltransferase, SAM-dependent |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: etgB (iron(II)-dependent oxidoreductase EgtB), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3703c etgB |
iron(II)-dependent oxidoreductase EgtB | 999 | 1000 ctx | neighborhood:881 fusion:893 cooccurence:773 coexpression:811 database:900 textmining:745 |
Rv3702c egtC |
amidohydrolase EgtC | 996 | 995 ctx | neighborhood:882 fusion:577 cooccurence:472 coexpression:819 |
Rv3704c gshA |
glutamate--cysteine ligase | 989 | 973 ctx | neighborhood:882 coexpression:733 textmining:616 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 982 | 955 ctx | neighborhood:839 coexpression:734 textmining:623 |
Rv1599 hisD |
histidinol dehydrogenase | 900 | 900 | database:900 |
Rv1861 |
transmembrane protein | 645 | 645 | coexpression:645 |
Rv3705c hyp |
hypothetical protein | 561 | 561 ctx | neighborhood:555 |
Rv1670 hyp |
hypothetical protein | 524 | 524 ctx | cooccurence:506 |
Rv0140 hyp |
hypothetical protein | 467 | 468 ctx | cooccurence:447 |
Rv0925c hyp |
hypothetical protein | 444 | 445 ctx | cooccurence:411 |
Rv0712 hyp |
hypothetical protein | 639 | 246 | textmining:541 |
Rv3680 |
anion transporter ATPase | 706 | 194 | textmining:651 |
Rv1464 csd |
cysteine desulfurase | 423 | 159 | |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 538 | 101 | textmining:508 |
Rv2593c ruvA |
Holliday junction ATP-dependent DNA helicase RuvA | 432 | 55 | textmining:424 |
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: histidine-specific methyltransferase EtgD
- MTBC0 PGAP product: L-histidine N(alpha)-methyltransferase
- Pfam (hmmscan --cut_ga): Methyltransf_33 PF10017.16 (E=6e-114)
- (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_218218.1)
- Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_33 (PF10017.16)
- 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
COG4301 - Curated reference: UniProt P9WN47 (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 —
27 functional partner(s); context anchor
etgB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003923|Rv3701c|egtD MRVSVANHLGEDAGHLALRRDVYSGLQKTPKSLPPKWFYDTVGSELFDQITRLPEYYPTRAEAEILRARSAEVASACRADTLVELGSGTSEKTRMLLDALRHRGSLRRFVPFDVDASVLSATATAIQREYSGVEINAVCGDFEEHLTEIPRGGRRLFVFLGSTIGNLTPGPRAQFLTALAGVMRPGDSLLLGTDLVKDAARLVRAYDDPGGVTAQFNRNVLAVINRELEADFDVDAFQHVARWNSAEERIEMWLRADGRQRVRVGALDLTVDFDAGEEMLTEVSCKFRPQAVGAELAAAGLHRIRWWTDEAGDFGLSLAAK