pheS Family assigned · medium auto-curated

H37Rv Rv1649 · MTBC0 - · 341 aa · 1858733–1859758 (+) · RefSeq NP_216165.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phenylalanine--tRNA ligase subunit alpha
MTBC0 PGAP re-annotation
Revised (this work)Phenylalanine--tRNA ligase subunit alpha. Pfam: Phe_tRNA-synt_N (PF02912.24), tRNA-synt_2d (PF01409.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WFU3 SwissProt · reviewed · Evidence at protein level
UniProt namePhenylalanine--tRNA ligase alpha subunit
EC (curated) EC 6.1.1.20

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namepheS
eggNOG descriptionBelongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 1 subfamily
Orthologous groupCOG0016
EC number EC 6.1.1.20
KEGG orthology K01889
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (61) GO:0003674, GO:0003824, GO:0004812, GO:0004826, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006139, GO:0006399 +49 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 0.173 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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)

PfamAccessioni-EvalueResiduesDescription
Phe_tRNA-synt_NPF02912.24 8.0e-1623–90 Aminoacyl tRNA synthetase class II, N-terminal domain
tRNA-synt_2dPF01409.26 3.9e-9595–334 tRNA synthetases class II core domain (F)

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: pheT (phenylalanine--tRNA ligase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 999 1000 ctx neighborhood:892 cooccurence:586 coexpression:998 experimental:999 database:963 textmining:965
Rv0708 rplP 50S ribosomal protein L16 820 792 coexpression:433 database:597
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 868 741 coexpression:648 textmining:514
Rv1647 adenylate cyclase 738 738 ctx neighborhood:737
Rv2783c gpsI bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase 818 702 coexpression:692 textmining:417
Rv2614c thrS threonine--tRNA ligase 753 678 coexpression:432
Rv0684 fusA1 elongation factor G 712 673 coexpression:515
Rv0683 rpsG 30S ribosomal protein S7 734 653 coexpression:652
Rv3419c gcp O-sialoglycoprotein endopeptidase 713 623 ctx cooccurence:590
Rv0685 tuf elongation factor Tu 724 621 coexpression:621
Rv2524c fas fatty acid synthase 596 596 coexpression:564
Rv0721 rpsE 30S ribosomal protein S5 651 590 coexpression:462
Rv0716 rplE 50S ribosomal protein L5 690 587 coexpression:514
Rv1689 tyrS tyrosine--tRNA ligase 683 587 coexpression:486
Rv1643 rplT 50S ribosomal protein L20 659 584

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): phenylalanine--tRNA ligase subunit alpha
  • Pfam (hmmscan --cut_ga): Phe_tRNA-synt_N PF02912.24 (E=8e-16), tRNA-synt_2d PF01409.26 (E=4e-95)
  • (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_216165.3)
  • Domains: Pfam-A via hmmscan --cut_ga — Phe_tRNA-synt_N (PF02912.24), tRNA-synt_2d (PF01409.26)
  • 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 COG0016
  • Curated reference: UniProt P9WFU3 (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 — 132 functional partner(s); context anchor pheT
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1649|pheS
MLSPEALTTAVDAAQQAIALADTLDVLARVKTEHLGDRSPLALARQALAVLPKEQRAEAGKRVNAARNAAQRSYDERLATLRAERDAAVLVAEGIDVTLPSTRVPAGARHPIIMLAEHVADTFIAMGWELAEGPEVETEQFNFDALNFPADHPARGEQDTFYIAPEDSRQLLRTHTSPVQIRTLLARELPVYIISIGRTFRTDELDATHTPIFHQVEGLAVDRGLSMAHLRGTLDAFARAEFGPSARTRIRPHFFPFTEPSAEVDVWFANKIGGAAWVEWGGCGMVHPNVLRATGIDPDLYSGFAFGMGLERTLQFRNGIPDMRDMVEGDVRFSLPFGVGA