glyA1 Resolved · high auto-curated
H37Rv Rv1093 · MTBC0 - ·
426 aa · 1220574–1221854 (+) ·
RefSeq YP_177787.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine hydroxymethyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Serine hydroxymethyltransferase. Pfam: SHMT (PF00464.26). |
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 |
P9WGI9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine hydroxymethyltransferase 1 |
| EC (curated) |
EC 2.1.2.1
|
| Curated function | Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Also exhibits THF-independent aldolase activity toward beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol mechanism. Thus, is able to catalyze the cleavage of L-allo-threonine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | glyA |
| eggNOG description | Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Also exhibits THF- independent aldolase activity toward beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol mechanism |
| Orthologous group | COG0112 |
| EC number |
EC 2.1.2.1
|
| KEGG orthology |
K00600
|
| KEGG pathways |
map00260, map00460, map00630, map00670, map00680, map01100, map01110, map01120, map01130, map01200, map01230, map01523
|
| KEGG modules |
M00140, M00141, M00346, M00532
|
| Gene Ontology (76) |
GO:0001505, GO:0003674, GO:0003824, GO:0004372, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006520 +64 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 | 0.604 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
SHMT | PF00464.26 | 4.1e-154 | 5–386 | Serine hydroxymethyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gcvT (aminomethyltransferase), high confidence from genomic context alone (score 990 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1832 gcvB |
glycine dehydrogenase | 996 | 992 | coexpression:911 database:900 textmining:511 |
Rv2211c gcvT |
aminomethyltransferase | 994 | 990 ctx | fusion:784 coexpression:475 database:900 textmining:450 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 983 | 976 | coexpression:729 database:900 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 982 | 971 | coexpression:651 database:900 textmining:415 |
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 966 | 952 | coexpression:453 database:900 |
Rv1826 gcvH |
glycine cleavage system protein H | 963 | 950 | coexpression:461 database:900 |
Rv0069c sdaA |
L-serine dehydratase | 964 | 925 | database:900 textmining:547 |
Rv1077 cbs |
cystathionine beta-synthase | 942 | 920 | database:900 |
Rv2754c thyX |
thymidylate synthase ThyX | 939 | 918 | database:900 |
Rv3042c serB2 |
phosphoserine phosphatase SerB | 952 | 917 | database:900 textmining:451 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 921 | 917 | database:900 |
Rv2964 purU |
formyltetrahydrofolate deformylase | 943 | 916 | database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 916 | 914 | database:900 |
Rv1613 trpA |
tryptophan synthase subunit alpha | 922 | 912 | database:900 |
Rv2763c dfrA |
dihydrofolate reductase | 920 | 910 | 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): serine hydroxymethyltransferase
- Pfam (hmmscan --cut_ga): SHMT PF00464.26 (E=4e-154)
- (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_177787.3)
- Domains: Pfam-A via hmmscan --cut_ga — SHMT (PF00464.26)
- 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
COG0112 - Curated reference: UniProt P9WGI9 (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 —
111 functional partner(s); context anchor
gcvT - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1093|glyA1 MSAPLAEVDPDIAELLAKELGRQRDTLEMIASENFVPRAVLQAQGSVLTNKYAEGLPGRRYYGGCEHVDVVENLARDRAKALFGAEFANVQPHSGAQANAAVLHALMSPGERLLGLDLANGGHLTHGMRLNFSGKLYENGFYGVDPATHLIDMDAVRATALEFRPKVIIAGWSAYPRVLDFAAFRSIADEVGAKLLVDMAHFAGLVAAGLHPSPVPHADVVSTTVHKTLGGGRSGLIVGKQQYAKAINSAVFPGQQGGPLMHVIAGKAVALKIAATPEFADRQRRTLSGARIIADRLMAPDVAKAGVSVVSGGTDVHLVLVDLRDSPLDGQAAEDLLHEVGITVNRNAVPNDPRPPMVTSGLRIGTPALATRGFGDTEFTEVADIIATALATGSSVDVSALKDRATRLARAFPLYDGLEEWSLVGR