thiD Resolved · high auto-curated
H37Rv Rv0422c · MTBC0 - ·
265 aa · 507758–508555 (-) ·
RefSeq NP_214936.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hydroxymethylpyrimidine/phosphomethylpyrimidine kinase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase. Pfam: Phos_pyr_kin (PF08543.18), PfkB (PF00294.30). |
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 |
P9WG77
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase |
| EC (curated) |
EC 2.7.1.49, EC 2.7.4.7
|
| Curated function | Catalyzes the phosphorylation of hydroxymethylpyrimidine phosphate (HMP-P) to HMP-PP, and of HMP to HMP-P. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | thiD |
| eggNOG description | Phosphomethylpyrimidine kinase |
| Orthologous group | COG0351 |
| EC number |
EC 2.7.1.49, EC 2.7.4.7
|
| KEGG orthology |
K00941
|
| 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 | 0.149 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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 |
|---|---|---|---|---|
Phos_pyr_kin | PF08543.18 | 7.4e-86 | 13–258 | Phosphomethylpyrimidine kinase |
PfkB | PF00294.30 | 3.3e-10 | 115–238 | pfkB family carbohydrate kinase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thiE (thiamine-phosphate synthase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0414c thiE |
thiamine-phosphate synthase | 999 | 999 ctx | fusion:895 cooccurence:765 coexpression:742 database:900 textmining:595 |
Rv0423c thiC |
phosphomethylpyrimidine synthase | 998 | 997 ctx | neighborhood:846 coexpression:806 database:900 |
Rv0421c hyp |
hypothetical protein | 970 | 971 ctx | neighborhood:882 coexpression:761 |
Rv0417 thiG |
thiazole synthase | 957 | 853 ctx | cooccurence:422 coexpression:715 textmining:725 |
Rv0416 thiS |
sulfur carrier protein ThiS | 812 | 813 | coexpression:781 |
Rv3211 rhlE |
ATP-dependent RNA helicase RhlE | 569 | 568 ctx | fusion:492 |
Rv2338c moeW |
molybdopterin biosynthesis protein MoeW | 584 | 550 | coexpression:428 |
Rv3859c gltB |
glutamate synthase large subunit | 542 | 542 ctx | neighborhood:538 |
Rv3455c truA |
tRNA pseudouridine synthase A | 539 | 539 | coexpression:501 |
Rv1253 deaD |
ATP-dependent RNA helicase DeaD | 525 | 525 ctx | fusion:447 |
Rv0427c xthA |
exodeoxyribonuclease III protein XthA | 517 | 517 | |
Rv1355c moeY |
molybdopterin biosynthesis protein MoeY | 552 | 516 | coexpression:430 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 633 | 501 | coexpression:433 |
Rv3116 moeB2 |
molybdenum cofactor biosynthesis protein MoeB | 631 | 498 | coexpression:430 |
Rv0420c |
transmembrane protein | 489 | 489 ctx | neighborhood:486 |
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): hydroxymethylpyrimidine/phosphomethylpyrimidine kinase
- Pfam (hmmscan --cut_ga): Phos_pyr_kin PF08543.18 (E=7e-86), PfkB PF00294.30 (E=3e-10)
- (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_214936.1)
- Domains: Pfam-A via hmmscan --cut_ga — Phos_pyr_kin (PF08543.18), PfkB (PF00294.30)
- 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
COG0351 - Curated reference: UniProt P9WG77 (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 —
43 functional partner(s); context anchor
thiE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0422c|thiD MTPPRVLSIAGSDSGGGAGIQADMRTMALLGVHACVAVTAVTVQNTLGVKDIHEVPNDVVAGQIEAVVTDIGVQAAKTGMLASSRIVATVAATWRRLELSVPLVVDPVCASMHGDPLLAPSALDSLRGQLFPLATLLTPNLDEARLLVDIEVVDAESQRAAAKALHALGPQWVLVKGGHLRSSDGSCDLLYDGVSCYQFDAQRLPTGDDHGGGDTLATAIAAALAHGFTVPDAVDFGKRWVTECLRAAYPLGRGHGPVSPLFRLS