gshA Resolved · high auto-curated
H37Rv Rv3704c · MTBC0 mtbc0_003926 ·
432 aa · 4170836–4172134 (-) ·
RefSeq NP_218221.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glutamate--cysteine ligase |
|---|---|
| MTBC0 PGAP re-annotation | ergothioneine biosynthesis glutamate--cysteine ligase EgtA |
| Revised (this work) | Ergothioneine biosynthesis glutamate--cysteine ligase EgtA. Pfam: GCS2 (PF04107.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPK7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glutamate--cysteine ligase EgtA |
| EC (curated) |
EC 6.3.2.2
|
| Curated function | Catalyzes the synthesis of gamma-glutamylcysteine (gamma-GC). This compound is used as substrate for the biosynthesis of the low-molecular thiol compound ergothioneine (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | egtA |
| eggNOG description | Catalyzes the synthesis of gamma-glutamylcysteine (gamma-GC). This compound is used as substrate for the biosynthesis of the low-molecular thiol compound ergothioneine |
| Orthologous group | COG3572 |
| EC number |
EC 6.3.2.2
|
| KEGG orthology |
K01919
|
| KEGG pathways |
map00270, map00480, map01100
|
| KEGG modules |
M00118
|
| Gene Ontology (12) |
GO:0003674, GO:0003824, GO:0004357, GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0016874, GO:0016879, GO:0016881, GO:0044464, GO:0071944
|
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 | 1.298 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 11 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 |
|---|---|---|---|---|
GCS2 | PF04107.19 | 1.1e-102 | 45–425 | Glutamate-cysteine ligase family 2(GCS2) |
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 992 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3703c etgB |
iron(II)-dependent oxidoreductase EgtB | 997 | 992 ctx | neighborhood:881 cooccurence:410 coexpression:797 database:500 textmining:745 |
Rv3702c egtC |
amidohydrolase EgtC | 988 | 988 ctx | neighborhood:882 cooccurence:631 coexpression:748 |
Rv3701c egtD |
histidine-specific methyltransferase EtgD | 989 | 973 ctx | neighborhood:882 coexpression:733 textmining:616 |
Rv0433 |
carboxylate-amine ligase | 903 | 903 | database:900 |
Rv2394 ggtB |
gamma-glutamyltranspeptidase precursor GgtB | 901 | 901 | database:900 |
Rv0773c ggtA |
bifunctional cephalosporin acylase/gamma-glutamyltranspeptidase | 900 | 901 | database:900 |
Rv2213 pepB |
cytosol aminopeptidase | 900 | 901 | database:900 |
Rv2467 pepN |
aminopeptidase PepN | 900 | 901 | database:900 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 900 | 901 | database:900 |
Rv0266c oplA |
5-oxoprolinase OplA | 900 | 900 | database:900 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 954 | 885 ctx | neighborhood:839 textmining:623 |
Rv2476c gdh |
NAD-dependent glutamate dehydrogenase | 805 | 806 | database:800 |
Rv0075 |
aminotransferase | 816 | 805 | database:800 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 814 | 805 | database:800 |
Rv3684 |
lyase | 803 | 804 | database:800 |
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: glutamate--cysteine ligase
- MTBC0 PGAP product: ergothioneine biosynthesis glutamate--cysteine ligase EgtA
- Pfam (hmmscan --cut_ga): GCS2 PF04107.19 (E=1e-102)
- (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_218221.1)
- Domains: Pfam-A via hmmscan --cut_ga — GCS2 (PF04107.19)
- 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
COG3572 - Curated reference: UniProt P9WPK7 (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
etgB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003926|Rv3704c|gshA MTLAAMTAAASQLDNAAPDDVEITDSSAAAEYIADGCLVDGPLGRVGLEMEAHCFDPADPFRRPSWEEITEVLEWLSPLPGGSVVSVEPGGAVELSGPPADGVLAAIGAMTRDQAVLRSALANAGLGLVFLGADPLRSPVRVNPGARYRAMEQFFAASHSGVPGAAMMTSTAAIQVNLDAGPQEGWAERVRLAHALGPTMIAIAANSPMLGGRFSGWQSTRQRVWGQMDSARCGPILGASGDHPGIDWAKYALKAPVMMVRSPDTQDTRAVTDYVPFTDWVDGRVLLDGRRATVADLVYHLTTLFPPVRPRQWLEIRYLDSVPDEVWPAVVFTLVTLLDDPVAADLAVDAVEPVATAWDTAARIGLADRRLYLAANRCLAIAARRVPTELIGAMQRLVDHVDRGVCPADDFSDRVIAGGIASAVTGMMHGAS