tsaE Family assigned · medium auto-curated

H37Rv Rv3422c · MTBC0 mtbc0_003636 · 168 aa · 3865130–3865636 (-) · RefSeq NP_217939.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)tRNA threonylcarbamoyladenosine biosynthesis protein
MTBC0 PGAP re-annotationtRNA (adenosine(37)-N6)-threonylcarbamoyltransferase complex ATPase subunit type 1 TsaE
Revised (this work)TRNA (adenosine(37)-N6)-threonylcarbamoyltransferase complex ATPase subunit type 1 TsaE. Pfam: TsaE (PF02367.24).

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

Curated reference (UniProt)

UniProt P9WFS7 SwissProt · reviewed · Evidence at protein level
UniProt nametRNA threonylcarbamoyladenosine biosynthesis protein TsaE
Curated functionRequired for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Is involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37, together with TsaD and TsaB. TsaE seems to play an indirect role in the t(6)A biosynthesis pathway, possibly in regulating the core enzymatic function of TsaD (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nametsaE
eggNOG descriptiontRNA threonylcarbamoyladenosine modification
Orthologous groupCOG0802
KEGG orthology K06925
Gene Ontology (2) GO:0008150, GO:0040007

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 0.38 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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
TsaEPF02367.24 8.8e-3126–155 Threonylcarbamoyl adenosine biosynthesis protein TsaE

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

Closest characterised functional partner: alr (alanine racemase), high confidence from genomic context alone (score 992 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3421c tsaB hyp hypothetical protein 999 996 ctx neighborhood:881 coexpression:777 experimental:803 textmining:895
Rv3423c alr alanine racemase 996 992 ctx neighborhood:882 fusion:695 coexpression:730 textmining:542
Rv3419c gcp O-sialoglycoprotein endopeptidase 999 990 ctx neighborhood:881 coexpression:553 experimental:790 textmining:922
Rv3420c rimI ribosomal-protein-alanine acetyltransferase RimI 985 889 ctx neighborhood:881 textmining:876
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 885 805 ctx neighborhood:544 coexpression:412 textmining:438
Rv3432c gadB glutamate decarboxylase GadB 620 620 ctx neighborhood:544
Rv0408 pta phosphate acetyltransferase 575 576 coexpression:413
Rv1301 threonylcarbamoyl-AMP synthase 650 543 database:500
Rv3418c groES chaperonin GroES 739 531 ctx neighborhood:531 textmining:467
Rv2367c ybeY endoribonuclease 523 523 ctx cooccurence:474
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 544 516 ctx neighborhood:442
Rv2727c miaA tRNA delta(2)-isopentenylpyrophosphate transferase 691 487 ctx cooccurence:440 textmining:424
Rv2977c thiL thiamine-monophosphate kinase 465 465 coexpression:421
Rv3417c groEL1 chaperonin GroEL 730 445 ctx neighborhood:445 textmining:534
Rv3424c hyp hypothetical protein 412 412 ctx neighborhood:408

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: tRNA threonylcarbamoyladenosine biosynthesis protein
  • MTBC0 PGAP product: tRNA (adenosine(37)-N6)-threonylcarbamoyltransferase complex ATPase subunit type 1 TsaE
  • Pfam (hmmscan --cut_ga): TsaE PF02367.24 (E=9e-31)
  • (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_217939.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TsaE (PF02367.24)
  • 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 COG0802
  • Curated reference: UniProt P9WFS7 (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 alr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003636|Rv3422c|tsaE
MSREGIRRRPKARAGLTGGGTATLPRVEDTLTLGSRLGEQLCAGDVVVLSGPLGAGKTVLAKGIAMAMDVEGPITSPTFVLARMHRPRRPGTPAMVHVDVYRLLDHNSADLLSELDSLDLDTDLEDAVVVVEWGEGLAERLSQRHLDVRLERVSHSDTRIATWSWGRS