glyA2 Resolved · high auto-curated
H37Rv Rv0070c · MTBC0 mtbc0_000077 ·
425 aa · 77764–79041 (-) ·
RefSeq NP_214584.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine hydroxymethyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | serine hydroxymethyltransferase |
| Revised (this work) | Serine hydroxymethyltransferase. Pfam: SHMT (PF00464.26), Aminotran_1_2 (PF00155.28), DegT_DnrJ_EryC1 (PF01041.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGI7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine hydroxymethyltransferase 2 |
| 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 (50) |
GO:0001505, GO:0003674, GO:0003824, GO:0004372, GO:0005488, GO:0005515, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006544 +38 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 | 0.769 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 9 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 | 1.1e-153 | 9–390 | Serine hydroxymethyltransferase |
Aminotran_1_2 | PF00155.28 | 2.0e-08 | 85–369 | Aminotransferase class I and II |
DegT_DnrJ_EryC1 | PF01041.24 | 4.9e-05 | 143–260 | DegT/DnrJ/EryC1/StrS aminotransferase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sdaA (L-serine dehydratase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0069c sdaA |
L-serine dehydratase | 998 | 997 ctx | neighborhood:801 coexpression:839 database:900 textmining:518 |
Rv1832 gcvB |
glycine dehydrogenase | 995 | 992 | coexpression:910 database:900 textmining:477 |
Rv2211c gcvT |
aminomethyltransferase | 994 | 991 ctx | fusion:792 coexpression:469 database:900 textmining:450 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 983 | 976 | coexpression:727 database:900 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 982 | 971 | coexpression:647 database:900 textmining:415 |
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 966 | 953 | coexpression:458 database:900 |
Rv1826 gcvH |
glycine cleavage system protein H | 963 | 950 | coexpression:458 database:900 |
Rv1077 cbs |
cystathionine beta-synthase | 945 | 919 | database:900 |
Rv2754c thyX |
thymidylate synthase ThyX | 940 | 919 | database:900 |
Rv3042c serB2 |
phosphoserine phosphatase SerB | 949 | 916 | database:900 textmining:421 |
Rv2964 purU |
formyltetrahydrofolate deformylase | 943 | 916 | database:900 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 919 | 915 | database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 916 | 913 | database:900 |
Rv1613 trpA |
tryptophan synthase subunit alpha | 921 | 911 | database:900 |
Rv2763c dfrA |
dihydrofolate reductase | 921 | 911 | 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: serine hydroxymethyltransferase
- MTBC0 PGAP product: serine hydroxymethyltransferase
- Pfam (hmmscan --cut_ga): SHMT PF00464.26 (E=1e-153), Aminotran_1_2 PF00155.28 (E=2e-08), DegT_DnrJ_EryC1 PF01041.24 (E=5e-05)
- (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_214584.1)
- Domains: Pfam-A via hmmscan --cut_ga — SHMT (PF00464.26), Aminotran_1_2 (PF00155.28), DegT_DnrJ_EryC1 (PF01041.24)
- 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 P9WGI7 (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 —
95 functional partner(s); context anchor
sdaA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000077|Rv0070c|glyA2 MNTLNDSLTAFDPDIAALIDGELRRQESGLEMIASENYAPLAVMQAQGSVLTNKYAEGYPGRRYYGGCEFVDGVEQLAIDRVKALFGAEYANVQPHSGATANAATMHALLNPGDTILGLSLAHGGHLTHGMRINFSGKLYHATAYEVSKEDYLVDMDAVAEAARTHRPKMIIAGWSAYPRQLDFARFRAIADEVDAVLMVDMAHFAGLVAAGVHPSPVPHAHVVTSTTHKTLGGPRGGIILCNDPAIAKKINSAVFPGQQGGPLEHVIAAKATAFKMAAQPEFAQRQQRCLDGARILAGRLTQPDVAERGIAVLTGGTDVHLVLVDLRDAELDGQQAEDRLAAVDITVNRNAVPFDPRPPMITSGLRIGTPALAARGFSHNDFRAVADLIAAALTATNDDQLGPLRAQVQRLAARYPLYPELHRT