thrS Resolved · high auto-curated

H37Rv Rv2614c · MTBC0 mtbc0_002782 · 692 aa · 2964742–2966820 (-) · RefSeq NP_217130.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)threonine--tRNA ligase
MTBC0 PGAP re-annotationthreonine--tRNA ligase
Revised (this work)Threonine--tRNA ligase. Pfam: tRNA_SAD (PF07973.20), tRNA-synt_2b (PF00587.31), HGTP_anticodon (PF03129.26).

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

Curated reference (UniProt)

UniProt P9WFT5 SwissProt · reviewed · Evidence at protein level
UniProt nameThreonine--tRNA ligase
EC (curated) EC 6.1.1.3
Curated functionCatalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: L-threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged L-seryl-tRNA(Thr).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namethrS
eggNOG descriptionCatalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction L-threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr)
Orthologous groupCOG0441
EC number EC 6.1.1.3
KEGG orthology K01868
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (61) GO:0003674, GO:0003824, GO:0004812, GO:0004829, 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 0.184 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 4 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
tRNA_SADPF07973.20 1.4e-11204–245 Threonyl and Alanyl tRNA synthetase second additional domain
tRNA-synt_2bPF00587.31 5.1e-45364–570 tRNA synthetase class II core domain (G, H, P, S and T)
HGTP_anticodonPF03129.26 1.2e-17582–671 Anticodon binding domain

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

Closest characterised functional partner: Rv2613c (AP-4-A phosphorylase), high confidence from genomic context alone (score 900 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2839c infB translation initiation factor IF-2 957 944 experimental:879
Rv0723 rplO 50S ribosomal protein L15 941 933 experimental:908
Rv2785c rpsO 30S ribosomal protein S15 930 909 experimental:899
Rv2613c AP-4-A phosphorylase 955 900 ctx neighborhood:881 textmining:569
Rv0979A rpmF 50S ribosomal protein L32 899 899 experimental:868
Rv0701 rplC 50S ribosomal protein L3 921 898 experimental:863
Rv0640 rplK 50S ribosomal protein L11 916 890 experimental:880
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 929 888 ctx neighborhood:881 textmining:400
Rv0706 rplV 50S ribosomal protein L22 914 888 experimental:860
Rv0708 rplP 50S ribosomal protein L16 893 887 experimental:792
Rv2611c phosphatidylinositol mannoside acyltransferase 920 881 ctx neighborhood:881
Rv2610c pimA alpha-(1-2)-phosphatidylinositol mannosyltransferase 887 881 ctx neighborhood:879
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 956 877 ctx neighborhood:544 coexpression:710 textmining:658
Rv0721 rpsE 30S ribosomal protein S5 889 877 experimental:810
Rv3442c rpsI 30S ribosomal protein S9 890 874 experimental:791

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: threonine--tRNA ligase
  • MTBC0 PGAP product: threonine--tRNA ligase
  • Pfam (hmmscan --cut_ga): tRNA_SAD PF07973.20 (E=1e-11), tRNA-synt_2b PF00587.31 (E=5e-45), HGTP_anticodon PF03129.26 (E=1e-17)
  • (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_217130.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA_SAD (PF07973.20), tRNA-synt_2b (PF00587.31), HGTP_anticodon (PF03129.26)
  • 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 COG0441
  • Curated reference: UniProt P9WFT5 (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 — 164 functional partner(s); context anchor Rv2613c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002782|Rv2614c|thrS
MSAPAQPAPGVDGGDPSQARIRVPAGTTAATAVGEAGLPRRGTPDAIVVVRDADGNLRDLSWVPDVDTDITPVAANTDDGRSVIRHSTAHVLAQAVQELFPQAKLGIGPPITDGFYYDFDVPEPFTPEDLAALEKRMRQIVKEGQLFDRRVYESTEQARAELANEPYKLELVDDKSGDAEIMEVGGDELTAYDNLNPRTRERVWGDLCRGPHIPTTKHIPAFKLTRSSAAYWRGDQKNASLQRIYGTAWESQEALDRHLEFIEEAQRRDHRKLGVELDLFSFPDEIGSGLAVFHPKGGIVRRELEDYSRRKHTEAGYQFVNSPHITKAQLFHTSGHLDWYADGMFPPMHIDAEYNADGSLRKPGQDYYLKPMNCPMHCLIFRARGRSYRELPLRLFEFGTVYRYEKSGVVHGLTRVRGLTMDDAHIFCTRDQMRDELRSLLRFVLDLLADYGLTDFYLELSTKDPEKFVGAEEVWEEATTVLAEVGAESGLELVPDPGGAAFYGPKISVQVKDALGRTWQMSTIQLDFNFPERFGLEYTAADGTRHRPVMIHRALFGSIERFFGILTEHYAGAFPAWLAPVQVVGIPVADEHVAYLEEVATQLKSHGVRAEVDASDDRMAKKIVHHTNHKVPFMVLAGDRDVAAGAVSFRFGDRTQINGVARDDAVAAIVAWIADRENAVPTAELVKVAGRE