asd Resolved · high auto-curated
H37Rv Rv3708c · MTBC0 mtbc0_003931 ·
345 aa · 4175128–4176165 (-) ·
RefSeq NP_218225.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | aspartate-semialdehyde dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | aspartate-semialdehyde dehydrogenase |
| Revised (this work) | Aspartate-semialdehyde dehydrogenase. Pfam: Semialdhyde_dh (PF01118.31), Semialdhyde_dhC (PF02774.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNX5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Aspartate-semialdehyde dehydrogenase |
| EC (curated) |
EC 1.2.1.11
|
| Curated function | Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate. Is essential for the growth and pathogenicity of M.tuberculosis, and for the generation of the bacterial cell wall. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | asd |
| eggNOG description | Catalyzes the NADPH-dependent formation of L-aspartate- semialdehyde (L-ASA) by the reductive dephosphorylation of L- aspartyl-4-phosphate |
| Orthologous group | COG0136 |
| EC number |
EC 1.2.1.11
|
| KEGG orthology |
K00133
|
| KEGG pathways |
map00260, map00261, map00270, map00300, map01100, map01110, map01120, map01130, map01210, map01230
|
| KEGG modules |
M00016, M00017, M00018, M00033, M00525, M00526, M00527
|
| Gene Ontology (48) |
GO:0003674, GO:0003824, GO:0004073, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006553, GO:0006807, GO:0008150 +36 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 | 0.121 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 2 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 |
|---|---|---|---|---|
Semialdhyde_dh | PF01118.31 | 3.0e-31 | 5–114 | Semialdehyde dehydrogenase, NAD binding domain |
Semialdhyde_dhC | PF02774.24 | 7.7e-45 | 139–328 | Semialdehyde dehydrogenase, dimerisation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ask (aspartokinase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3709c ask |
aspartokinase | 999 | 998 ctx | neighborhood:882 coexpression:778 database:900 textmining:958 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 996 | 972 ctx | cooccurence:497 coexpression:450 database:900 textmining:877 |
Rv1294 thrA |
homoserine dehydrogenase | 984 | 964 | coexpression:427 database:900 textmining:593 |
Rv2726c dapF |
diaminopimelate epimerase | 969 | 767 | coexpression:677 textmining:875 |
Rv3707c hyp |
hypothetical protein | 757 | 757 ctx | neighborhood:755 |
Rv2773c dapB |
4-hydroxy-tetrahydrodipicolinate reductase | 937 | 744 ctx | cooccurence:466 coexpression:502 textmining:767 |
Rv3710 leuA |
2-isopropylmalate synthase | 738 | 713 ctx | neighborhood:614 |
Rv1296 thrB |
homoserine kinase | 743 | 664 | coexpression:427 |
Rv1293 lysA |
diaminopimelate decarboxylase | 933 | 633 ctx | cooccurence:518 textmining:827 |
Rv1437 pgk |
phosphoglycerate kinase | 621 | 587 | experimental:462 |
Rv1295 thrC |
threonine synthase | 642 | 533 | coexpression:432 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' | 523 | 524 | coexpression:401 |
Rv3706c hyp |
hypothetical protein | 524 | 523 ctx | neighborhood:522 |
Rv1640c lysX |
bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase | 515 | 516 | coexpression:401 |
Rv3859c gltB |
glutamate synthase large subunit | 841 | 506 | coexpression:478 textmining:691 |
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: aspartate-semialdehyde dehydrogenase
- MTBC0 PGAP product: aspartate-semialdehyde dehydrogenase
- Pfam (hmmscan --cut_ga): Semialdhyde_dh PF01118.31 (E=3e-31), Semialdhyde_dhC PF02774.24 (E=8e-45)
- (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_218225.1)
- Domains: Pfam-A via hmmscan --cut_ga — Semialdhyde_dh (PF01118.31), Semialdhyde_dhC (PF02774.24)
- 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
COG0136 - Curated reference: UniProt P9WNX5 (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 —
79 functional partner(s); context anchor
ask - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003931|Rv3708c|asd MGLSIGIVGATGQVGQVMRTLLDERDFPASAVRFFASARSQGRKLAFRGQEIEVEDAETADPSGLDIALFSAGSAMSKVQAPRFAAAGVTVIDNSSAWRKDPDVPLVVSEVNFERDAHRRPKGIIANPNCTTMAAMPVLKVLHDEARLVRLVVSSYQAVSGSGLAGVAELAEQARAVIGGAEQLVYDGGALEFPPPNTYVAPIAFNVVPLAGSLVDDGSGETDEDQKLRFESRKILGIPDLLVSGTCVRVPVFTGHSLSINAEFAQPLSPERARELLDGATGVQLVDVPTPLAAAGVDESLVGRIRRDPGVPDGRGLALFVSGDNLRKGAALNTIQIAELLTADL