tmk Resolved · high auto-curated
H37Rv Rv3247c · MTBC0 mtbc0_003455 ·
216 aa · 3649562–3650212 (-) ·
RefSeq NP_217764.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | thymidylate kinase |
|---|---|
| MTBC0 PGAP re-annotation | dTMP kinase |
| Revised (this work) | DTMP kinase. Pfam: Thymidylate_kin (PF02223.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKE1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Thymidylate kinase |
| EC (curated) |
EC 2.7.4.9
|
| Curated function | Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | tmk |
| eggNOG description | Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis |
| Orthologous group | COG0125 |
| EC number |
EC 2.7.4.9
|
| KEGG orthology |
K00943
|
| KEGG pathways |
map00240, map01100
|
| KEGG modules |
M00053
|
| Gene Ontology (125) |
GO:0000166, GO:0000287, GO:0001882, GO:0001883, GO:0003674, GO:0003824, GO:0004798, GO:0005488, GO:0005515, GO:0005524, GO:0005525, GO:0005575 +113 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 | 0.55 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 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 |
|---|---|---|---|---|
Thymidylate_kin | PF02223.24 | 1.3e-21 | 7–189 | Thymidylate kinase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mtrA (two component DNA-binding response regulator MtrA), high confidence from genomic context alone (score 794 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2697c dut |
deoxyuridine 5'-triphosphate nucleotidohydrolase | 949 | 929 | database:900 |
Rv3051c nrdE |
ribonucleoside-diphosphate reductase subunit alpha | 943 | 923 | database:900 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 932 | 923 | database:900 |
Rv2754c thyX |
thymidylate synthase ThyX | 932 | 921 | database:900 |
Rv2764c thyA |
thymidylate synthase ThyA | 940 | 918 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 927 | 906 | database:900 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB | 913 | 904 | database:900 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 | 913 | 904 | database:900 |
Rv3048c nrdF2 |
ribonucleoside-diphosphate reductase subunit beta NrdF2 | 913 | 904 | database:900 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 794 | 794 ctx | neighborhood:794 |
Rv3248c sahH |
adenosylhomocysteinase | 801 | 778 ctx | neighborhood:775 |
Rv3244c lpqB |
lipoprotein LpqB | 748 | 749 ctx | neighborhood:748 |
Rv3249c |
TetR family transcriptional regulator | 703 | 703 ctx | neighborhood:703 |
Rv3438 hyp |
hypothetical protein | 662 | 663 ctx | cooccurence:661 |
Rv3311 hyp |
hypothetical protein | 618 | 618 ctx | cooccurence:618 |
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: thymidylate kinase
- MTBC0 PGAP product: dTMP kinase
- Pfam (hmmscan --cut_ga): Thymidylate_kin PF02223.24 (E=1e-21)
- (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_217764.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thymidylate_kin (PF02223.24)
- 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
COG0125 - Curated reference: UniProt P9WKE1 (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 —
70 functional partner(s); context anchor
mtrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003455|Rv3247c|tmk MAVLIAIEGVDGAGKRTLVEKLSGAFRAAGRSVATLAFPRYGQSVAADIAAEALHGEHGDLASSVYAMATLFALDRAGAVHTIQGLCRGYDVVILDRYVASNAAYSAARLHENAAGKAAAWVQRIEFARLGLPKPDWQVLLAVSAELAGERSRGRAQRDPGRARDNYERDAELQQRTGAVYAELAAQGWGGRWLVVGADVDPGRLAATLAPPDVPS