alaS Resolved · high auto-curated
H37Rv Rv2555c · MTBC0 mtbc0_002723 ·
904 aa · 2897316–2900030 (-) ·
RefSeq NP_217071.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alanine--tRNA ligase |
|---|---|
| MTBC0 PGAP re-annotation | alanine--tRNA ligase |
| Revised (this work) | Alanine--tRNA ligase. Pfam: tRNA-synt_2c (PF01411.25), tRNA_SAD (PF07973.20), DHHA1 (PF02272.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFW7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Alanine--tRNA ligase |
| EC (curated) |
EC 6.1.1.7
|
| Curated function | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) via its editing domain. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | alaS |
| eggNOG description | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction alanine is first activated by ATP to form Ala- AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) via its editing domain |
| Orthologous group | COG0013 |
| EC number |
EC 6.1.1.7
|
| KEGG orthology |
K01872
|
| KEGG pathways |
map00970
|
| KEGG modules |
M00359, M00360
|
| Gene Ontology (78) |
GO:0003674, GO:0003824, GO:0004812, GO:0004813, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +66 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 | 0.256 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
tRNA-synt_2c | PF01411.25 | 2.2e-198 | 5–574 | tRNA synthetases class II (A) |
tRNA_SAD | PF07973.20 | 2.6e-16 | 673–717 | Threonyl and Alanyl tRNA synthetase second additional domain |
DHHA1 | PF02272.25 | 1.7e-13 | 792–897 | DHHA1 domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ruvX (Holliday junction resolvase), high confidence from genomic context alone (score 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2554c ruvX |
Holliday junction resolvase | 993 | 981 ctx | neighborhood:881 coexpression:826 textmining:652 |
Rv2553c mltG |
membrane protein | 939 | 940 ctx | neighborhood:881 coexpression:514 |
Rv1691 hyp |
hypothetical protein | 925 | 920 | experimental:775 database:644 |
Rv3529c hyp |
hypothetical protein | 925 | 920 | experimental:775 database:644 |
Rv2267c stf3 hyp |
hypothetical protein | 925 | 919 | experimental:775 database:644 |
Rv2552c aroE |
shikimate 5-dehydrogenase | 888 | 888 ctx | neighborhood:881 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 969 | 852 | coexpression:703 textmining:800 |
Rv3812 PE_PGRS62 |
PE-PGRS family protein PE_PGRS62 | 848 | 836 | experimental:570 database:622 |
Rv2328 PE23 |
PE family protein PE23 | 848 | 836 | experimental:570 database:622 |
Rv3036c TB22.2 hyp |
hypothetical protein | 848 | 836 | experimental:570 database:622 |
Rv0832 PE_PGRS12 |
PE-PGRS family protein PE_PGRS12 | 848 | 836 | experimental:570 database:622 |
Rv2614c thrS |
threonine--tRNA ligase | 857 | 813 ctx | cooccurence:436 coexpression:636 |
Rv2551c hyp |
hypothetical protein | 797 | 797 ctx | neighborhood:791 |
Rv2572c aspS |
aspartate--tRNA ligase | 829 | 792 | coexpression:684 |
Rv2556c hyp |
hypothetical protein | 789 | 789 ctx | neighborhood:779 |
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: alanine--tRNA ligase
- MTBC0 PGAP product: alanine--tRNA ligase
- Pfam (hmmscan --cut_ga): tRNA-synt_2c PF01411.25 (E=2e-198), tRNA_SAD PF07973.20 (E=3e-16), DHHA1 PF02272.25 (E=2e-13)
- (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_217071.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_2c (PF01411.25), tRNA_SAD (PF07973.20), DHHA1 (PF02272.25)
- 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
COG0013 - Curated reference: UniProt P9WFW7 (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 —
150 functional partner(s); context anchor
ruvX - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002723|Rv2555c|alaS MQTHEIRKRFLDHFVKAGHTEVPSASVILDDPNLLFVNAGMVQFVPFFLGQRTPPYPTATSIQKCIRTPDIDEVGITTRHNTFFQMAGNFSFGDYFKRGAIELAWALLTNSLAAGGYGLDPERIWTTVYFDDDEAVRLWQEVAGLPAERIQRRGMADNYWSMGIPGPCGPSSEIYYDRGPEFGPAGGPIVSEDRYLEVWNLVFMQNERGEGTTKEDYQILGPLPRKNIDTGMGVERIALVLQDVHNVYETDLLRPVIDTVARVAARAYDVGNHEDDVRYRIIADHSRTAAILIGDGVSPGNDGRGYVLRRLLRRVIRSAKLLGIDAAIVGDLMATVRNAMGPSYPELVADFERISRIAVAEETAFNRTLASGSRLFEEVASSTKKSGATVLSGSDAFTLHDTYGFPIELTLEMAAETGLQVDEIGFRELMAEQRRRAKADAAARKHAHADLSAYRELVDAGATEFTGFDELRSQARILGIFVDGKRVPVVAHGVAGGAGEGQRVELVLDRTPLYAESGGQIADEGTISGTGSSEAARAAVTDVQKIAKTLWVHRVNVESGEFVEGDTVIAAVDPGWRRGATQGHSGTHMVHAALRQVLGPNAVQAGSLNRPGYLRFDFNWQGPLTDDQRTQVEEVTNEAVQADFEVRTFTEQLDKAKAMGAIALFGESYPDEVRVVEMGGPFSLELCGGTHVSNTAQIGPVTILGESSIGSGVRRVEAYVGLDSFRHLAKERALMAGLASSLKVPSEEVPARVANLVERLRAAEKELERVRMASARAAATNAAAGAQRIGNVRLVAQRMSGGMTAADLRSLIGDIRGKLGSEPAVVALIAEGESQTVPYAVAANPAAQDLGIRANDLVKQLAVAVEGRGGGKADLAQGSGKNPTGIDAALDAVRSEIAVIARVG