thrB Resolved · high auto-curated
H37Rv Rv1296 · MTBC0 mtbc0_001388 ·
316 aa · 1461036–1461986 (+) ·
RefSeq NP_215812.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | homoserine kinase |
|---|---|
| MTBC0 PGAP re-annotation | homoserine kinase |
| Revised (this work) | Homoserine kinase. Pfam: GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKE7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Homoserine kinase |
| EC (curated) |
EC 2.7.1.39
|
| Curated function | Catalyzes the ATP-dependent phosphorylation of L-homoserine to L-homoserine phosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | thrB |
| eggNOG description | Catalyzes the ATP-dependent phosphorylation of L- homoserine to L-homoserine phosphate |
| Orthologous group | COG0083 |
| EC number |
EC 2.7.1.39
|
| KEGG orthology |
K00872
|
| KEGG pathways |
map00260, map01100, map01110, map01120, map01230
|
| KEGG modules |
M00018
|
| Gene Ontology (55) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0004413, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520 +43 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 | 0.225 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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 |
|---|---|---|---|---|
GHMP_kinases_N | PF00288.33 | 4.7e-14 | 69–154 | GHMP kinases N terminal domain |
GHMP_kinases_C | PF08544.19 | 1.6e-05 | 231–283 | GHMP kinases C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thrC (threonine synthase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1295 thrC |
threonine synthase | 999 | 998 ctx | neighborhood:731 coexpression:920 database:900 textmining:709 |
Rv1294 thrA |
homoserine dehydrogenase | 999 | 997 ctx | neighborhood:731 coexpression:875 database:900 textmining:843 |
Rv0809 purM |
phosphoribosylformylglycinamidine cyclo-ligase PurM | 909 | 899 ctx | fusion:898 |
Rv0069c sdaA |
L-serine dehydratase | 860 | 843 | database:800 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 866 | 827 | database:800 |
Rv2124c metH |
methionine synthase | 894 | 826 | database:800 textmining:421 |
Rv1293 lysA |
diaminopimelate decarboxylase | 948 | 819 ctx | neighborhood:731 textmining:725 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 839 | 818 | database:800 |
Rv1079 metB |
cystathionine gamma-synthase | 838 | 817 | database:800 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 818 | 811 | database:800 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 888 | 809 | database:800 textmining:441 |
Rv0075 |
aminotransferase | 806 | 807 | database:800 |
Rv2335 cysE |
serine acetyltransferase | 830 | 802 | database:800 |
Rv3248c sahH |
adenosylhomocysteinase | 802 | 802 | database:800 |
Rv1077 cbs |
cystathionine beta-synthase | 822 | 801 | 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: homoserine kinase
- MTBC0 PGAP product: homoserine kinase
- Pfam (hmmscan --cut_ga): GHMP_kinases_N PF00288.33 (E=5e-14), GHMP_kinases_C PF08544.19 (E=2e-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_215812.1)
- Domains: Pfam-A via hmmscan --cut_ga — GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19)
- 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
COG0083 - Curated reference: UniProt P9WKE7 (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 —
58 functional partner(s); context anchor
thrC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001388|Rv1296|thrB MVTQALLPSGLVASAVVAASSANLGPGFDSVGLALSLYDEIIVETTDSGLTVTVDGEGGDQVPLGPEHLVVRAVQHGLQAAGVSAAGLAVRCRNAIPHSRGLGSSAAAVVGGLAAVNGLVVQTDSSPSSDAELIQLASEFEGHPDNAAAAVLGGAVVSWTDHSGDRPNYSAVSLRLHPDIRLFTAIPEQRSSTAETRVLLPAQVSHDDARFNVSRAALLVVALTERPDLLMAATEDLLHQPQRAAAMTASAEYLRLLRRHNVAAALSGAGPSLIALSTDSELPTDAVEFGAAKGFAVTELTVGEAVRWSPTVRVPG