serA1 Resolved · high auto-curated
H37Rv Rv2996c · MTBC0 - ·
528 aa · 3353483–3355069 (-) ·
RefSeq YP_177916.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-3-phosphoglycerate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | D-3-phosphoglycerate dehydrogenase. Pfam: 2-Hacid_dh (PF00389.37), 2-Hacid_dh_C (PF02826.26), NAD_binding_2 (PF03446.22), PGDH_inter (PF19304.5), ACT (PF01842.32). |
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 |
P9WNX3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | D-3-phosphoglycerate dehydrogenase |
| EC (curated) |
EC 1.1.1.399, EC 1.1.1.95
|
| Curated function | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | serA |
| eggNOG description | D-isomer specific 2-hydroxyacid dehydrogenase |
| Orthologous group | COG0111 |
| EC number |
EC 1.1.1.399, EC 1.1.1.95
|
| KEGG orthology |
K00058
|
| KEGG pathways |
map00260, map00680, map01100, map01120, map01130, map01200, map01230
|
| KEGG modules |
M00020
|
| Gene Ontology (43) |
GO:0003674, GO:0003824, GO:0004617, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006563, GO:0006564, GO:0006807 +31 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 | 0.481 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
2-Hacid_dh | PF00389.37 | 2.0e-38 | 6–313 | D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain |
2-Hacid_dh_C | PF02826.26 | 4.7e-62 | 107–281 | D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
NAD_binding_2 | PF03446.22 | 9.8e-05 | 143–231 | NAD binding domain of 6-phosphogluconate dehydrogenase |
PGDH_inter | PF19304.5 | 2.8e-17 | 323–443 | D-3-phosphoglycerate dehydrogenase intervening domain |
ACT | PF01842.32 | 6.4e-09 | 456–516 | ACT domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: leuB (3-isopropylmalate dehydrogenase), high confidence from genomic context alone (score 976 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0884c serC |
phosphoserine aminotransferase | 992 | 979 | coexpression:729 database:900 textmining:628 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 979 | 976 ctx | neighborhood:869 coexpression:826 |
Rv0728c serA2 |
D-3-phosphoglycerate dehydrogenase SerA | 937 | 921 | database:900 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 924 | 916 | database:900 |
Rv2997 |
dehydrogenase | 595 | 593 ctx | neighborhood:586 |
Rv1295 thrC |
threonine synthase | 627 | 583 | coexpression:477 |
Rv3002c ilvN |
acetolactate synthase small subunit | 605 | 581 | coexpression:404 |
Rv1294 thrA |
homoserine dehydrogenase | 632 | 578 | coexpression:422 |
Rv0708 rplP |
50S ribosomal protein L16 | 573 | 573 | experimental:446 |
Rv0719 rplF |
50S ribosomal protein L6 | 539 | 540 | experimental:533 |
Rv2089c pepE |
dipeptidase PepE | 538 | 538 | |
Rv2535c pepQ |
cytoplasmic peptidase PepQ | 535 | 536 | |
Rv3001c ilvC |
ketol-acid reductoisomerase | 556 | 528 | coexpression:413 |
Rv1286 cysC |
adenylyl-sulfate kinase | 566 | 501 | coexpression:501 |
Rv2540c aroF |
chorismate synthase | 517 | 496 | coexpression:423 |
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): D-3-phosphoglycerate dehydrogenase
- Pfam (hmmscan --cut_ga): 2-Hacid_dh PF00389.37 (E=2e-38), 2-Hacid_dh_C PF02826.26 (E=5e-62), NAD_binding_2 PF03446.22 (E=1e-04), PGDH_inter PF19304.5 (E=3e-17), ACT PF01842.32 (E=6e-09)
- (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_177916.1)
- Domains: Pfam-A via hmmscan --cut_ga — 2-Hacid_dh (PF00389.37), 2-Hacid_dh_C (PF02826.26), NAD_binding_2 (PF03446.22), PGDH_inter (PF19304.5), 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
COG0111 - Curated reference: UniProt P9WNX3 (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 —
70 functional partner(s); context anchor
leuB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2996c|serA1 MSLPVVLIADKLAPSTVAALGDQVEVRWVDGPDRDKLLAAVPEADALLVRSATTVDAEVLAAAPKLKIVARAGVGLDNVDVDAATARGVLVVNAPTSNIHSAAEHALALLLAASRQIPAADASLREHTWKRSSFSGTEIFGKTVGVVGLGRIGQLVAQRIAAFGAYVVAYDPYVSPARAAQLGIELLSLDDLLARADFISVHLPKTPETAGLIDKEALAKTKPGVIIVNAARGGLVDEAALADAITGGHVRAAGLDVFATEPCTDSPLFELAQVVVTPHLGASTAEAQDRAGTDVAESVRLALAGEFVPDAVNVGGGVVNEEVAPWLDLVRKLGVLAGVLSDELPVSLSVQVRGELAAEEVEVLRLSALRGLFSAVIEDAVTFVNAPALAAERGVTAEICKASESPNHRSVVDVRAVGADGSVVTVSGTLYGPQLSQKIVQINGRHFDLRAQGINLIIHYVDRPGALGKIGTLLGTAGVNIQAAQLSEDAEGPGATILLRLDQDVPDDVRTAIAAAVDAYKLEVVDLS