metB Resolved · high auto-curated
H37Rv Rv1079 · MTBC0 mtbc0_001159 ·
388 aa · 1212336–1213502 (+) ·
RefSeq NP_215595.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cystathionine gamma-synthase |
|---|---|
| MTBC0 PGAP re-annotation | cystathionine gamma-synthase |
| Revised (this work) | Cystathionine gamma-synthase. Pfam: Cys_Met_Meta_PP (PF01053.27), Met_gamma_lyase (PF06838.18), DegT_DnrJ_EryC1 (PF01041.24), Aminotran_1_2 (PF00155.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGB7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cystathionine gamma-synthase |
| EC (curated) |
EC 2.5.1.48
|
| Curated function | Catalyzes the formation of L-cystathionine from O-succinyl-L-homoserine (OSHS) and L-cysteine, via a gamma-replacement reaction (By similarity). In the absence of thiol, catalyzes gamma-elimination to form 2-oxobutanoate, succinate and ammonia. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | metB |
| eggNOG description | cystathionine |
| Orthologous group | COG0626 |
| EC number |
EC 2.5.1.48
|
| KEGG orthology |
K01739
|
| KEGG pathways |
map00270, map00450, map00920, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00017
|
| Gene Ontology (60) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0003962, GO:0004123, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +48 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 | 0.472 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 |
|---|---|---|---|---|
Cys_Met_Meta_PP | PF01053.27 | 1.4e-148 | 16–387 | Cys/Met metabolism PLP-dependent enzyme |
Met_gamma_lyase | PF06838.18 | 2.7e-06 | 53–229 | Methionine gamma-lyase |
DegT_DnrJ_EryC1 | PF01041.24 | 3.5e-08 | 62–238 | DegT/DnrJ/EryC1/StrS aminotransferase family |
Aminotran_1_2 | PF00155.28 | 1.4e-04 | 83–192 | Aminotransferase class I and II |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cbs (cystathionine beta-synthase), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1077 cbs |
cystathionine beta-synthase | 995 | 993 ctx | neighborhood:556 cooccurence:403 coexpression:714 database:900 textmining:482 |
Rv2124c metH |
methionine synthase | 987 | 969 | coexpression:644 database:900 textmining:618 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 971 | 957 | coexpression:467 database:900 |
Rv3684 |
lyase | 964 | 953 | coexpression:466 database:900 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 977 | 946 | coexpression:461 database:900 textmining:601 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 949 | 936 | database:900 |
Rv2391 sirA |
sulfite reductase | 965 | 931 | database:900 textmining:518 |
Rv0075 |
aminotransferase | 951 | 931 | database:900 |
Rv2294 |
cystathionine beta-lyase | 950 | 930 | database:900 |
Rv3341 metA |
homoserine O-acetyltransferase | 952 | 922 | database:900 textmining:419 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 927 | 918 | database:900 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 972 | 917 | database:900 textmining:682 |
Rv3248c sahH |
adenosylhomocysteinase | 929 | 917 | database:900 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 925 | 916 | database:900 |
Rv0331 |
dehydrogenase/reductase | 912 | 904 | database:900 |
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: cystathionine gamma-synthase
- MTBC0 PGAP product: cystathionine gamma-synthase
- Pfam (hmmscan --cut_ga): Cys_Met_Meta_PP PF01053.27 (E=1e-148), Met_gamma_lyase PF06838.18 (E=3e-06), DegT_DnrJ_EryC1 PF01041.24 (E=4e-08), Aminotran_1_2 PF00155.28 (E=1e-04)
- (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_215595.1)
- Domains: Pfam-A via hmmscan --cut_ga — Cys_Met_Meta_PP (PF01053.27), Met_gamma_lyase (PF06838.18), DegT_DnrJ_EryC1 (PF01041.24), Aminotran_1_2 (PF00155.28)
- 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
COG0626 - Curated reference: UniProt P9WGB7 (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 —
52 functional partner(s); context anchor
cbs - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001159|Rv1079|metB MSEDRTGHQGISGPATRAIHAGYRPDPATGAVNVPIYASSTFAQDGVGGLRGGFEYARTGNPTRAALEASLAAVEEGAFARAFSSGMAATDCALRAMLRPGDHVVIPDDAYGGTFRLIDKVFTRWDVQYTPVRLADLDAVGAAITPRTRLIWVETPTNPLLSIADITAIAELGTDRSAKVLVDNTFASPALQQPLRLGADVVLHSTTKYIGGHSDVVGGALVTNDEELDEEFAFLQNGAGAVPGPFDAYLTMRGLKTLVLRMQRHSENACAVAEFLADHPSVSSVLYPGLPSHPGHEIAARQMRGFGGMVSVRMRAGRRAAQDLCAKTRVFILAESLGGVESLIEHPSAMTHASTAGSQLEVPDDLVRLSVGIEDIADLLGDLEQALG