thiL Resolved · high auto-curated

H37Rv Rv2977c · MTBC0 mtbc0_003162 · 333 aa · 3353960–3354961 (-) · RefSeq NP_217493.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)thiamine-monophosphate kinase
MTBC0 PGAP re-annotationthiamine-phosphate kinase
Revised (this work)Thiamine-phosphate kinase. Pfam: AIRS (PF00586.30), AIRS_C (PF02769.28).

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

Curated reference (UniProt)

UniProt P9WG71 SwissProt · reviewed · Evidence at protein level
UniProt nameThiamine-monophosphate kinase
EC (curated) EC 2.7.4.16
Curated functionCatalyzes the ATP-dependent phosphorylation of thiamine-monophosphate (TMP) to form thiamine-pyrophosphate (TPP), the active form of vitamin B1.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namethiL
eggNOG descriptionCatalyzes the ATP-dependent phosphorylation of thiamine- monophosphate (TMP) to form thiamine-pyrophosphate (TPP), the active form of vitamin B1
Orthologous groupCOG0611
EC number EC 2.7.4.16
KEGG orthology K00946
KEGG pathways map00730, map01100
KEGG modules M00127
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 0.862 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 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
AIRSPF00586.30 1.0e-2142–152 AIR synthase related protein, N-terminal domain
AIRS_CPF02769.28 2.0e-05166–250 AIR synthase related protein, C-terminal domain

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

Closest characterised functional partner: tnpB (transposase), high confidence from genomic context alone (score 978 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2978c tnpB transposase 978 978 ctx neighborhood:882 coexpression:824
Rv2979c resolvase 967 967 ctx neighborhood:882 coexpression:732
Rv3585 radA DNA repair protein RadA 943 943 coexpression:943
Rv0414c thiE thiamine-phosphate synthase 944 908 database:900 textmining:419
Rv0733 adk adenylate kinase 902 902 database:900
Rv3228 rsgA hyp hypothetical protein 913 901 database:900
Rv2976c ung uracil-DNA glycosylase 851 852 ctx neighborhood:836
Rv0606 Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to 801 802 coexpression:801
Rv2885c transposase 798 799 coexpression:798
Rv0605 IS1536 family serine type transposase 754 754 coexpression:754
Rv3644c DNA polymerase 733 734 coexpression:733
Rv0185 hyp hypothetical protein 732 732 coexpression:732
Rv2791c tnpB transposase 732 732 coexpression:731
Rv2980 hyp hypothetical protein 585 585 ctx neighborhood:585
Rv2736c recX regulatory protein RecX 559 560 coexpression:524

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: thiamine-monophosphate kinase
  • MTBC0 PGAP product: thiamine-phosphate kinase
  • Pfam (hmmscan --cut_ga): AIRS PF00586.30 (E=1e-21), AIRS_C PF02769.28 (E=2e-05)
  • (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_217493.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AIRS (PF00586.30), AIRS_C (PF02769.28)
  • 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 COG0611
  • Curated reference: UniProt P9WG71 (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 — 41 functional partner(s); context anchor tnpB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003162|Rv2977c|thiL
MTTKDHSLATESPTLQQLGEFAVIDRLVRGRRQPATVLLGPGDDAALVSAGDGRTVVSTDMLVQDSHFRLDWSTPQDVGRKAIAQNAADIEAMGARATAFVVGFGAPAETPAAQASALVDGMWEEAGRIGAGIVGGDLVSCRQWVVSVTAIGDLDGRAPVLRSGAKAGSVLAVVGELGRSAAGYALWCNGIEDFAELRRRHLVPQPPYGHGAAAAAVGAQAMIDVSDGLLADLRHIAEASGVRIDLSAAALAADRDALTAAATALGTDPWPWVLSGGEDHALVACFVGPVPAGWRTIGRVLDGPARVLVDGEEWTGYAGWQSFGEPDNQGSLG