thrA Resolved · high auto-curated
H37Rv Rv1294 · MTBC0 mtbc0_001386 ·
441 aa · 1458414–1459739 (+) ·
RefSeq NP_215810.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | homoserine dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | homoserine dehydrogenase |
| Revised (this work) | Homoserine dehydrogenase. Pfam: NAD_binding_3 (PF03447.23), Homoserine_dh (PF00742.25), ACT (PF01842.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPX1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Homoserine dehydrogenase |
| EC (curated) |
EC 1.1.1.3
|
| Curated function | Catalyzes the conversion of L-aspartate-beta-semialdehyde (L-Asa) to L-homoserine (L-Hse), the third step in the biosynthesis of threonine and methionine from aspartate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | hom |
| eggNOG description | homoserine dehydrogenase |
| Orthologous group | COG0460 |
| EC number |
EC 1.1.1.3, EC 2.7.2.4
|
| KEGG orthology |
K00003, K12524
|
| KEGG pathways |
map00260, map00261, map00270, map00300, map01100, map01110, map01120, map01130, map01230
|
| KEGG modules |
M00016, M00017, M00018, M00526, M00527
|
| Gene Ontology (10) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044464, GO:0071944
|
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 | 0.073 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 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 |
|---|---|---|---|---|
NAD_binding_3 | PF03447.23 | 2.3e-23 | 14–131 | Homoserine dehydrogenase, NAD binding domain |
Homoserine_dh | PF00742.25 | 9.0e-64 | 139–322 | Homoserine dehydrogenase |
ACT | PF01842.32 | 6.9e-08 | 355–424 | ACT domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thrB (homoserine kinase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1296 thrB |
homoserine kinase | 999 | 997 ctx | neighborhood:731 coexpression:875 database:900 textmining:843 |
Rv1295 thrC |
threonine synthase | 999 | 996 ctx | neighborhood:881 coexpression:958 textmining:794 |
Rv3708c asd |
aspartate-semialdehyde dehydrogenase | 984 | 964 | coexpression:427 database:900 textmining:593 |
Rv3341 metA |
homoserine O-acetyltransferase | 951 | 944 | database:900 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 962 | 939 | database:900 textmining:409 |
Rv1293 lysA |
diaminopimelate decarboxylase | 949 | 928 ctx | neighborhood:881 |
Rv2124c metH |
methionine synthase | 958 | 913 | coexpression:428 database:800 textmining:542 |
Rv3709c ask |
aspartokinase | 972 | 910 ctx | cooccurence:588 coexpression:420 experimental:415 textmining:707 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 915 | 899 | coexpression:404 database:800 |
Rv1292 argS |
arginine--tRNA ligase | 896 | 891 ctx | neighborhood:881 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 926 | 884 | coexpression:412 database:800 |
Rv1079 metB |
cystathionine gamma-synthase | 935 | 882 | coexpression:402 database:800 textmining:478 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 888 | 872 | database:800 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 883 | 868 | database:800 |
Rv0069c sdaA |
L-serine dehydratase | 846 | 839 | 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 dehydrogenase
- MTBC0 PGAP product: homoserine dehydrogenase
- Pfam (hmmscan --cut_ga): NAD_binding_3 PF03447.23 (E=2e-23), Homoserine_dh PF00742.25 (E=9e-64), ACT PF01842.32 (E=7e-08)
- (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_215810.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_3 (PF03447.23), Homoserine_dh (PF00742.25), ACT (PF01842.32)
- 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
COG0460 - Curated reference: UniProt P9WPX1 (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 —
82 functional partner(s); context anchor
thrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001386|Rv1294|thrA MPGDEKPVGVAVLGLGNVGSEVVRIIENSAEDLAARVGAPLVLRGIGVRRVTTDRGVPIELLTDDIEELVAREDVDIVVEVMGPVEPSRKAILGALERGKSVVTANKALLATSTGELAQAAESAHVDLYFEAAVAGAIPVIRPLTQSLAGDTVLRVAGIVNGTTNYILSAMDSTGADYASALADASALGYAEADPTADVEGYDAAAKAAILASIAFHTRVTADDVYREGITKVTPADFGSAHALGCTIKLLSICERITTDEGSQRVSARVYPALVPLSHPLAAVNGAFNAVVVEAEAAGRLMFYGQGAGGAPTASAVTGDLVMAARNRVLGSRGPRESKYAQLPVAPMGFIETRYYVSMNVADKPGVLSAVAAEFAKREVSIAEVRQEGVVDEGGRRVGARIVVVTHLATDAALSETVDALDDLDVVQGVSSVIRLEGTGL