ask Resolved · high auto-curated
H37Rv Rv3709c · MTBC0 mtbc0_003932 ·
421 aa · 4176166–4177431 (-) ·
RefSeq NP_218226.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | aspartokinase |
|---|---|
| MTBC0 PGAP re-annotation | aspartate kinase |
| Revised (this work) | Aspartate kinase. Pfam: AA_kinase (PF00696.34), ACT (PF01842.32), ACT_7 (PF13840.13), ACT_9 (PF22468.3). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPX3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Aspartokinase |
| EC (curated) |
EC 2.7.2.4
|
| Curated function | Catalyzes the phosphorylation of the beta-carboxyl group of aspartic acid with ATP to yield 4-phospho-L-aspartate, which is involved in the branched biosynthetic pathway leading to the biosynthesis of amino acids lysine, threonine, isoleucine and methionine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | ask |
| eggNOG description | Belongs to the aspartokinase family |
| Orthologous group | COG0527 |
| EC number |
EC 2.7.2.4
|
| KEGG orthology |
K00928
|
| KEGG pathways |
map00260, map00261, map00270, map00300, map01100, map01110, map01120, map01130, map01210, map01230
|
| KEGG modules |
M00016, M00017, M00018, M00033, M00525, M00526, M00527
|
| Gene Ontology (55) |
GO:0003674, GO:0003824, GO:0004072, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006520, GO:0006553 +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 | 0.52 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
AA_kinase | PF00696.34 | 3.1e-55 | 3–231 | Amino acid kinase family |
ACT | PF01842.32 | 5.0e-11 | 267–330 | ACT domain |
ACT_7 | PF13840.13 | 1.9e-14 | 341–403 | ACT domain |
ACT_9 | PF22468.3 | 1.9e-21 | 347–405 | ACT domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: asd (aspartate-semialdehyde dehydrogenase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3708c asd |
aspartate-semialdehyde dehydrogenase | 999 | 998 ctx | neighborhood:882 coexpression:778 database:900 textmining:958 |
Rv1294 thrA |
homoserine dehydrogenase | 972 | 910 ctx | cooccurence:588 coexpression:420 experimental:415 textmining:707 |
Rv2201 asnB |
asparagine synthetase | 898 | 882 | coexpression:402 database:800 |
Rv0357c purA |
adenylosuccinate synthetase | 858 | 854 | database:800 |
Rv1658 argG |
argininosuccinate synthase | 871 | 838 | database:800 |
Rv1595 nadB |
L-aspartate oxidase | 824 | 815 | database:800 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 821 | 804 | database:800 |
Rv1538c ansA |
L-aparaginase | 867 | 802 | database:800 |
Rv1295 thrC |
threonine synthase | 830 | 779 | coexpression:725 |
Rv3707c hyp |
hypothetical protein | 757 | 758 ctx | neighborhood:755 |
Rv1296 thrB |
homoserine kinase | 890 | 751 | coexpression:650 textmining:579 |
Rv3710 leuA |
2-isopropylmalate synthase | 761 | 735 ctx | neighborhood:614 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 959 | 722 ctx | cooccurence:523 textmining:862 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 733 | 718 | coexpression:717 |
Rv2773c dapB |
4-hydroxy-tetrahydrodipicolinate reductase | 918 | 683 ctx | cooccurence:598 textmining:754 |
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: aspartokinase
- MTBC0 PGAP product: aspartate kinase
- Pfam (hmmscan --cut_ga): AA_kinase PF00696.34 (E=3e-55), ACT PF01842.32 (E=5e-11), ACT_7 PF13840.13 (E=2e-14), ACT_9 PF22468.3 (E=2e-21)
- (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_218226.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_kinase (PF00696.34), ACT (PF01842.32), ACT_7 (PF13840.13), ACT_9 (PF22468.3)
- 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
COG0527 - Curated reference: UniProt P9WPX3 (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 —
84 functional partner(s); context anchor
asd - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003932|Rv3709c|ask MALVVQKYGGSSVADAERIRRVAERIVATKKQGNDVVVVVSAMGDTTDDLLDLAQQVCPAPPPRELDMLLTAGERISNALVAMAIESLGAHARSFTGSQAGVITTGTHGNAKIIDVTPGRLQTALEEGRVVLVAGFQGVSQDTKDVTTLGRGGSDTTAVAMAAALGADVCEIYTDVDGIFSADPRIVRNARKLDTVTFEEMLEMAACGAKVLMLRCVEYARRHNIPVHVRSSYSDRPGTVVVGSIKDVPMEDPILTGVAHDRSEAKVTIVGLPDIPGYAAKVFRAVADADVNIDMVLQNVSKVEDGKTDITFTCSRDVGPAAVEKLDSLRNEIGFSQLLYDDHIGKVSLIGAGMRSHPGVTATFCEALAAVGVNIELISTSEIRISVLCRDTELDKAVVALHEAFGLGGDEEATVYAGTGR