ald Resolved · high auto-curated
H37Rv Rv2780 · MTBC0 mtbc0_002959 ·
371 aa · 3109235–3110350 (+) ·
RefSeq NP_217296.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | L-alanine dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | alanine dehydrogenase |
| Revised (this work) | Alanine dehydrogenase. Pfam: AlaDh_PNT_N (PF05222.22), AlaDh_PNT_C (PF01262.28), Shikimate_DH (PF01488.27), 2-Hacid_dh_C (PF02826.26), GIDA (PF01134.29), NAD_binding_2 (PF03446.22), Pyr_redox (PF00070.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQB1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Alanine dehydrogenase |
| EC (curated) |
EC 1.4.1.1
|
| Curated function | Catalyzes the reversible reductive amination of pyruvate to L-alanine. However, since the physiological environment of M.tuberculosis has a neutral pH, it can be assumed that the enzyme catalyzes exclusively the formation of L-alanine. May play a role in cell wall synthesis as L-alanine is an important constituent of the peptidoglycan layer. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | ald |
| eggNOG description | Belongs to the AlaDH PNT family |
| Orthologous group | COG0686 |
| EC number |
EC 1.4.1.1
|
| KEGG orthology |
K00259
|
| KEGG pathways |
map00250, map00430, map01100
|
| Gene Ontology (53) |
GO:0000286, GO:0001666, GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +41 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) pseudogene candidate
| pN/pS | 0.239 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 12.03% of strains (17467) · clonal |
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 |
|---|---|---|---|---|
AlaDh_PNT_N | PF05222.22 | 3.9e-48 | 4–137 | Alanine dehydrogenase/PNT, N-terminal domain |
AlaDh_PNT_C | PF01262.28 | 3.1e-85 | 141–351 | Alanine dehydrogenase/PNT, C-terminal domain |
Shikimate_DH | PF01488.27 | 1.5e-05 | 167–269 | Shikimate / quinate 5-dehydrogenase |
2-Hacid_dh_C | PF02826.26 | 1.5e-06 | 168–268 | D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
GIDA | PF01134.29 | 7.3e-05 | 170–207 | Glucose inhibited division protein A |
NAD_binding_2 | PF03446.22 | 2.5e-05 | 171–267 | NAD binding domain of 6-phosphogluconate dehydrogenase |
Pyr_redox | PF00070.34 | 9.7e-05 | 171–219 | Pyridine nucleotide-disulphide oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pntB (NAD(P) transhydrogenase subunit beta PntB), high confidence from genomic context alone (score 908 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3423c alr |
alanine racemase | 972 | 957 | coexpression:779 database:800 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 907 | 908 ctx | fusion:900 |
Rv0337c aspC |
aspartate aminotransferase | 927 | 901 | database:900 |
Rv2779c |
Lrp/AsnC family transcriptional regulator | 837 | 620 ctx | neighborhood:618 textmining:589 |
Rv2778c hyp |
hypothetical protein | 513 | 514 ctx | neighborhood:512 |
Rv1188 |
proline dehydrogenase | 446 | 261 | |
Rv1832 gcvB |
glycine dehydrogenase | 512 | 191 | textmining:422 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 423 | 85 | |
Rv0491 regX3 |
two component sensory transduction protein RegX | 513 | 70 | textmining:498 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 408 | 64 | |
Rv0846c mmcO |
oxidase | 418 | 60 | textmining:407 |
Rv2220 glnA1 |
glutamine synthetase | 464 | 52 | textmining:458 |
Rv3133c devR |
two component transcriptional regulator DevR | 438 | 52 | textmining:432 |
Rv2222c glnA2 |
glutamine synthetase | 428 | 52 | textmining:422 |
Rv3859c gltB |
glutamate synthase large subunit | 716 | 49 | textmining:714 |
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: L-alanine dehydrogenase
- MTBC0 PGAP product: alanine dehydrogenase
- Pfam (hmmscan --cut_ga): AlaDh_PNT_N PF05222.22 (E=4e-48), AlaDh_PNT_C PF01262.28 (E=3e-85), Shikimate_DH PF01488.27 (E=2e-05), 2-Hacid_dh_C PF02826.26 (E=2e-06), GIDA PF01134.29 (E=7e-05), NAD_binding_2 PF03446.22 (E=3e-05), Pyr_redox PF00070.34 (E=1e-04)
- (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_217296.1)
- Domains: Pfam-A via hmmscan --cut_ga — AlaDh_PNT_N (PF05222.22), AlaDh_PNT_C (PF01262.28), Shikimate_DH (PF01488.27), 2-Hacid_dh_C (PF02826.26), GIDA (PF01134.29), NAD_binding_2 (PF03446.22), Pyr_redox (PF00070.34)
- 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
COG0686 - Curated reference: UniProt P9WQB1 (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 —
18 functional partner(s); context anchor
pntB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002959|Rv2780|ald MRVGIPTETKNNEFRVAITPAGVAELTRRGHEVLIQAGAGEGSAITDADFKAAGAQLVGTADQVWADADLLLKVKEPIAAEYGRLRHGQILFTFLHLAASRACTDALLDSGTTSIAYETVQTADGALPLLAPMSEVAGRLAAQVGAYHLMRTQGGRGVLMGGVPGVEPADVVVIGAGTAGYNAARIANGMGATVTVLDINIDKLRQLDAEFCGRIHTRYSSAYELEGAVKRADLVIGAVLVPGAKAPKLVSNSLVAHMKPGAVLVDIAIDQGGCFEGSRPTTYDHPTFAVHDTLFYCVANMPASVPKTSTYALTNATMPYVLELADHGWRAACRSNPALAKGLSTHEGALLSERVATDLGVPFTEPASVLA