cbs Resolved · high auto-curated
H37Rv Rv1077 · MTBC0 - ·
464 aa · 1201717–1203111 (+) ·
RefSeq YP_177782.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cystathionine beta-synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cystathionine beta-synthase. Pfam: PALP (PF00291.32), CBS (PF00571.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WP51
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable cystathionine beta-synthase Rv1077 |
| EC (curated) |
EC 4.2.1.22
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismK Transcription
|
|---|---|
| Preferred name | cbs |
| eggNOG description | Cystathionine beta-synthase |
| Orthologous group | COG0031 |
| EC number |
EC 4.2.1.22
|
| KEGG orthology |
K01697
|
| KEGG pathways |
map00260, map00270, map01100, map01130, map01230
|
| KEGG modules |
M00035, M00338
|
| Gene Ontology (25) |
GO:0003674, GO:0005488, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0008144, GO:0016020, GO:0019842 +13 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 | 0.514 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 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 |
|---|---|---|---|---|
PALP | PF00291.32 | 1.8e-71 | 7–296 | Pyridoxal-phosphate dependent enzyme |
CBS | PF00571.34 | 4.7e-06 | 407–458 | CBS domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: metB (cystathionine gamma-synthase), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1079 metB |
cystathionine gamma-synthase | 995 | 993 ctx | neighborhood:556 cooccurence:403 coexpression:714 database:900 textmining:482 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 984 | 980 | coexpression:713 database:900 |
Rv2335 cysE |
serine acetyltransferase | 975 | 957 | coexpression:481 database:800 textmining:461 |
Rv3248c sahH |
adenosylhomocysteinase | 941 | 934 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 942 | 920 | database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 945 | 919 | database:900 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 934 | 914 | database:900 |
Rv1559 ilvA |
threonine dehydratase IlvA | 925 | 914 | database:900 |
Rv2124c metH |
methionine synthase | 937 | 911 | database:900 |
Rv3042c serB2 |
phosphoserine phosphatase SerB | 943 | 908 | database:900 textmining:411 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 928 | 906 | database:900 |
Rv1613 trpA |
tryptophan synthase subunit alpha | 915 | 906 | database:900 |
Rv0069c sdaA |
L-serine dehydratase | 926 | 905 | database:900 |
Rv2294 |
cystathionine beta-lyase | 912 | 904 | database:900 |
Rv0075 |
aminotransferase | 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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cystathionine beta-synthase
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=2e-71), CBS PF00571.34 (E=5e-06)
- (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 YP_177782.1)
- Domains: Pfam-A via hmmscan --cut_ga — PALP (PF00291.32), CBS (PF00571.34)
- 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
COG0031 - Curated reference: UniProt P9WP51 (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 —
64 functional partner(s); context anchor
metB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1077|cbs MRIAQHISELIGGTPLVRLNSVVPDGAGTVAAKVEYLNPGGSSKDRIAVKMIEAAEASGQLKPGGTIVEPTSGNTGVGLALVAQRRGYKCVFVCPDKVSEDKRNVLIAYGAEVVVCPTAVPPHDPASYYSVSDRLVRDIDGAWKPDQYANPEGPASHYVTTGPEIWADTEGKVTHFVAGIGTGGTITGAGRYLKEVSGGRVRIVGADPEGSVYSGGAGRPYLVEGVGEDFWPAAYDPSVPDEIIAVSDSDSFDMTRRLAREEAMLVGGSCGMAVVAALKVAEEAGPDALIVVLLPDGGRGYMSKIFNDAWMSSYGFLRSRLDGSTEQSTVGDVLRRKSGALPALVHTHPSETVRDAIGILREYGVSQMPVVGAEPPVMAGEVAGSVSERELLSAVFEGRAKLADAVSAHMSPPLRMIGAGELVSAAGKALRDWDALMVVEEGKPVGVITRYDLLGFLSEGAGRR