ansA Resolved · high auto-curated
H37Rv Rv1538c · MTBC0 mtbc0_001645 ·
326 aa · 1751021–1752001 (-) ·
RefSeq NP_216054.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | L-aparaginase |
|---|---|
| MTBC0 PGAP re-annotation | asparaginase |
| Revised (this work) | Asparaginase. Pfam: Asparaginase (PF00710.26), Asparaginase_C (PF17763.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPX5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | L-asparaginase |
| EC (curated) |
EC 3.5.1.1
|
| Curated function | Has a dual function in both nitrogen assimilation and in protection against acid stress during infection through asparagine hydrolysis and NH4(+) release. Catalyzes asparagine hydrolysis. Cannot use glutamine. Required for intracellular survival inside macrophages during host colonization. Mediates phagosome acidification arrest and resistance to acid stress through the formation of acid-neutralizing NH4(+) ions. In addition, may induce stress to primary immune cells and compromise the host immune response. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismJ Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | ansA |
| eggNOG description | Asparaginase |
| Orthologous group | COG0252 |
| EC number |
EC 3.5.1.1
|
| KEGG orthology |
K01424
|
| KEGG pathways |
map00250, map00460, map01100, map01110
|
| Gene Ontology (47) |
GO:0003674, GO:0003824, GO:0004067, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520, GO:0006528, GO:0006530 +35 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 | 1.155 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
Asparaginase | PF00710.26 | 1.1e-45 | 14–179 | Asparaginase, N-terminal |
Asparaginase_C | PF17763.7 | 1.6e-19 | 210–318 | Glutaminase/Asparaginase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1540 (RNA pseudouridine synthase), high confidence from genomic context alone (score 790 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1658 argG |
argininosuccinate synthase | 924 | 907 | database:900 |
Rv1595 nadB |
L-aspartate oxidase | 918 | 905 | database:900 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 906 | 902 | database:900 |
Rv2201 asnB |
asparagine synthetase | 914 | 901 | database:900 |
Rv0357c purA |
adenylosuccinate synthetase | 900 | 901 | database:900 |
Rv3432c gadB |
glutamate decarboxylase GadB | 935 | 806 | database:800 textmining:682 |
Rv3601c panD |
aspartate 1-decarboxylase | 875 | 802 | database:800 |
Rv3709c ask |
aspartokinase | 867 | 802 | database:800 |
Rv1540 |
RNA pseudouridine synthase | 789 | 790 ctx | neighborhood:788 |
Rv1539 lspA |
lipoprotein signal peptidase | 809 | 789 ctx | neighborhood:788 |
Rv3396c guaA |
GMP synthase | 552 | 553 | |
Rv0640 rplK |
50S ribosomal protein L11 | 409 | 410 | coexpression:410 |
Rv3565 aspB |
aspartate aminotransferase AspB | 845 | 187 | textmining:818 |
Rv2903c lepB |
signal peptidase | 552 | 127 | textmining:508 |
Rv0337c aspC |
aspartate aminotransferase | 586 | 114 | textmining:552 |
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-aparaginase
- MTBC0 PGAP product: asparaginase
- Pfam (hmmscan --cut_ga): Asparaginase PF00710.26 (E=1e-45), Asparaginase_C PF17763.7 (E=2e-19)
- (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_216054.1)
- Domains: Pfam-A via hmmscan --cut_ga — Asparaginase (PF00710.26), Asparaginase_C (PF17763.7)
- 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
COG0252 - Curated reference: UniProt P9WPX5 (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 —
19 functional partner(s); context anchor
Rv1540 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001645|Rv1538c|ansA MGANHVRNDPIMARLTVITTGGTISTTAGPDGVLRPTHCGATLIAGLDMDSDIEVVDLMALDSSKLTPADWDRIGAAVQEAFRGGADGVVITHGTDTLEETALWLDLTYAGSRPVVLTGAMLSADAPGADGPANLRDALAVAADPAARDLGVLVSFGGRVLQPLGLHKVANPDLCGFAGESLGFTSGGVRLTRTKTRPYLGDLGAAVAPRVDIVAVYPGSDAVAMDACVAAGARAVVLEALGSGNAGAAVIEGVRRHCRDGSDPVVIAVSTRVAGARVGAGYGPGHDLVEAGAVMVPRLPPSQARVLLMAALAANSPVADVIDRWG