folK Resolved · high auto-curated
H37Rv Rv3606c · MTBC0 mtbc0_003824 ·
188 aa · 4071885–4072451 (-) ·
RefSeq NP_218123.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase |
|---|---|
| MTBC0 PGAP re-annotation | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase |
| Revised (this work) | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase. Pfam: HPPK (PF01288.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNC7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase |
| EC (curated) |
EC 2.7.6.3
|
| Curated function | Catalyzes the transfer of pyrophosphate from adenosine triphosphate (ATP) to 6-hydroxymethyl-7,8-dihydropterin, an enzymatic step in folate biosynthesis pathway. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | folK |
| eggNOG description | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase |
| Orthologous group | COG0801 |
| EC number |
EC 2.7.6.3, EC 4.1.2.25
|
| KEGG orthology |
K00950, K13940
|
| KEGG pathways |
map00790, map01100
|
| KEGG modules |
M00126, M00841
|
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 | 0.553 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
HPPK | PF01288.26 | 1.1e-30 | 5–139 | 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folB (dihydroneopterin aldolase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3607c folB |
dihydroneopterin aldolase | 999 | 1000 ctx | neighborhood:882 fusion:864 cooccurence:712 coexpression:974 database:900 textmining:718 |
Rv3608c folP1 |
dihydropteroate synthase | 999 | 1000 ctx | neighborhood:882 cooccurence:758 coexpression:945 database:900 textmining:571 |
Rv3609c folE |
GTP cyclohydrolase I | 998 | 997 ctx | neighborhood:836 cooccurence:580 coexpression:957 textmining:586 |
Rv1207 folP2 |
dihydropteroate synthase | 996 | 993 ctx | cooccurence:753 coexpression:731 database:900 textmining:518 |
Rv3605c hyp |
hypothetical protein | 882 | 882 ctx | neighborhood:882 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 832 | 817 ctx | neighborhood:790 |
Rv3604c |
transmembrane protein | 737 | 737 ctx | neighborhood:734 |
Rv3600c coaX |
type III pantothenate kinase | 596 | 597 ctx | neighborhood:594 |
Rv3601c panD |
aspartate 1-decarboxylase | 640 | 595 ctx | neighborhood:594 |
Rv3611 |
Rv3611, (MTCY07H7B.11c), len: 217 aa. Hypothetical unknown arg-, pro-rich protein. Possible ORF containing several direct repeats. | 546 | 546 ctx | neighborhood:544 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 544 | 515 | coexpression:476 |
Rv3602c panC |
pantothenate synthetase | 638 | 502 ctx | neighborhood:427 |
Rv3907c pcnA |
poly(A) polymerase PcnA | 500 | 489 | coexpression:447 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 689 | 487 | coexpression:445 textmining:419 |
Rv0013 trpG |
anthranilate synthase component II | 507 | 481 |
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: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase
- MTBC0 PGAP product: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase
- Pfam (hmmscan --cut_ga): HPPK PF01288.26 (E=1e-30)
- (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_218123.1)
- Domains: Pfam-A via hmmscan --cut_ga — HPPK (PF01288.26)
- 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
COG0801 - Curated reference: UniProt P9WNC7 (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 —
31 functional partner(s); context anchor
folB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003824|Rv3606c|folK MTRVVLSVGSNLGDRLARLRSVADGLGDALIAASPIYEADPWGGVEQGQFLNAVLIADDPTCEPREWLRRAQEFERAAGRVRGQRWGPRNLDVDLIACYQTSATEALVEVTARENHLTLPHPLAHLRAFVLIPWIAVDPTAQLTVAGCPRPVTRLLAELEPADRDSVRLFRPSFDLNSRHPVSRAPES