lysA Resolved · high auto-curated
H37Rv Rv1293 · MTBC0 mtbc0_001385 ·
447 aa · 1457067–1458410 (+) ·
RefSeq NP_215809.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | diaminopimelate decarboxylase |
|---|---|
| MTBC0 PGAP re-annotation | diaminopimelate decarboxylase |
| Revised (this work) | Diaminopimelate decarboxylase. Pfam: Orn_Arg_deC_N (PF02784.23), Orn_DAP_Arg_deC (PF00278.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIU7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Diaminopimelate decarboxylase |
| EC (curated) |
EC 4.1.1.20
|
| Curated function | Specifically catalyzes the decarboxylation of meso-diaminopimelate (meso-DAP) to L-lysine (Probable). Is essential for the viability of M.tuberculosis in the host. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | lysA |
| eggNOG description | Specifically catalyzes the decarboxylation of meso- diaminopimelate (meso-DAP) to L-lysine |
| Orthologous group | COG1166 |
| EC number |
EC 4.1.1.20
|
| KEGG orthology |
K01586
|
| KEGG pathways |
map00300, map01100, map01110, map01120, map01130, map01230
|
| KEGG modules |
M00016, M00525, M00526, M00527
|
| Gene Ontology (55) |
GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006082, GO:0006520, GO:0006553, GO:0006807, GO:0008144, GO:0008150 +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 | 0.348 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
Orn_Arg_deC_N | PF02784.23 | 1.0e-55 | 48–306 | Pyridoxal-dependent decarboxylase, pyridoxal binding domain |
Orn_DAP_Arg_deC | PF00278.29 | 1.1e-15 | 313–403 | Pyridoxal-dependent decarboxylase, C-terminal sheet domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dapF (diaminopimelate epimerase), high confidence from genomic context alone (score 972 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2726c dapF |
diaminopimelate epimerase | 996 | 972 ctx | cooccurence:643 database:900 textmining:886 |
Rv1294 thrA |
homoserine dehydrogenase | 949 | 928 ctx | neighborhood:881 |
Rv2158c murE |
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase | 921 | 911 | database:900 |
Rv1292 argS |
arginine--tRNA ligase | 912 | 903 ctx | neighborhood:882 |
Rv1295 thrC |
threonine synthase | 915 | 889 ctx | neighborhood:882 |
Rv2773c dapB |
4-hydroxy-tetrahydrodipicolinate reductase | 979 | 825 ctx | cooccurence:755 textmining:890 |
Rv1296 thrB |
homoserine kinase | 948 | 819 ctx | neighborhood:731 textmining:725 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 961 | 817 ctx | cooccurence:752 textmining:800 |
Rv1178 dapC |
aminotransferase | 876 | 759 ctx | cooccurence:595 coexpression:409 textmining:510 |
Rv3696c glpK |
glycerol kinase | 740 | 688 | database:642 |
Rv2115c mpa |
proteasome-associated ATPase | 664 | 651 | database:645 |
Rv1334 mec |
[CysO | 656 | 636 | database:632 |
Rv3708c asd |
aspartate-semialdehyde dehydrogenase | 933 | 633 ctx | cooccurence:518 textmining:827 |
Rv2109c prcA |
proteasome subunit alpha | 633 | 620 | database:598 |
Rv2110c prcB |
proteasome subunit beta | 621 | 607 | database:598 |
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: diaminopimelate decarboxylase
- MTBC0 PGAP product: diaminopimelate decarboxylase
- Pfam (hmmscan --cut_ga): Orn_Arg_deC_N PF02784.23 (E=1e-55), Orn_DAP_Arg_deC PF00278.29 (E=1e-15)
- (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_215809.1)
- Domains: Pfam-A via hmmscan --cut_ga — Orn_Arg_deC_N (PF02784.23), Orn_DAP_Arg_deC (PF00278.29)
- 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
COG1166 - Curated reference: UniProt P9WIU7 (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 —
86 functional partner(s); context anchor
dapF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001385|Rv1293|lysA MNELLHLAPNVWPRNTTRDEVGVVCIAGIPLTQLAQEYGTPLFVIDEDDFRSRCRETAAAFGSGANVHYAAKAFLCSEVARWISEEGLCLDVCTGGELAVALHASFPPERITLHGNNKSVSELTAAVKAGVGHIVVDSMTEIERLDAIAGEAGIVQDVLVRLTVGVEAHTHEFISTAHEDQKFGLSVASGAAMAAVRRVFATDHLRLVGLHSHIGSQIFDVDGFELAAHRVIGLLRDVVGEFGPEKTAQIATVDLGGGLGISYLPSDDPPPIAELAAKLGTIVSDESTAVGLPTPKLVVEPGRAIAGPGTITLYEVGTVKDVDVSATAHRRYVSVDGGMSDNIRTALYGAQYDVRLVSRVSDAPPVPARLVGKHCESGDIIVRDTWVPDDIRPGDLVAVAATGAYCYSLSSRYNMVGRPAVVAVHAGNARLVLRRETVDDLLSLEVR