Rv0992c Resolved · high auto-curated
H37Rv Rv0992c · MTBC0 mtbc0_001063 ·
197 aa · 1115914–1116507 (-) ·
RefSeq NP_215507.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 5-formyltetrahydrofolate cyclo-ligase |
|---|---|
| MTBC0 PGAP re-annotation | 5-formyltetrahydrofolate cyclo-ligase |
| Revised (this work) | 5-formyltetrahydrofolate cyclo-ligase. Pfam: 5-FTHF_cyc-lig (PF01812.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05575
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 5-formyltetrahydrofolate cyclo-ligase |
| EC (curated) |
EC 6.3.3.2
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ygfA |
| eggNOG description | Belongs to the 5-formyltetrahydrofolate cyclo-ligase family |
| Orthologous group | COG0212 |
| EC number |
EC 6.3.3.2
|
| KEGG orthology |
K01934
|
| KEGG pathways |
map00670, map01100
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 8 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 |
|---|---|---|---|---|
5-FTHF_cyc-lig | PF01812.27 | 1.3e-50 | 6–186 | 5-formyltetrahydrofolate cyclo-ligase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: galU (UTP--glucose-1-phosphate uridylyltransferase), high confidence from genomic context alone (score 781 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 929 | 922 | database:900 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 929 | 908 | database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 908 | 904 | database:900 |
Rv0991c hyp |
hypothetical protein | 791 | 792 ctx | neighborhood:791 |
Rv0993 galU |
UTP--glucose-1-phosphate uridylyltransferase | 792 | 781 ctx | neighborhood:781 |
Rv0994 moeA1 |
molybdopterin molybdenumtransferase 1 | 732 | 719 ctx | neighborhood:718 |
Rv0995 rimJ |
ribosomal-protein-alanine acetyltransferase RimJ | 696 | 696 ctx | neighborhood:680 |
Rv0996 |
transmembrane protein | 636 | 636 ctx | neighborhood:636 |
Rv0990c hyp |
hypothetical protein | 544 | 544 ctx | neighborhood:541 |
Rv3859c gltB |
glutamate synthase large subunit | 526 | 527 ctx | neighborhood:522 |
Rv0110 |
integral membrane protein | 523 | 523 | coexpression:496 |
Rv1337 |
integral membrane protein | 521 | 522 | coexpression:495 |
Rv1088 PE9 |
PE family protein PE9 | 422 | 422 | coexpression:422 |
Rv0803 purL |
phosphoribosylformylglycinamidine synthase 2 | 406 | 407 | coexpression:403 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 563 | 385 |
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: 5-formyltetrahydrofolate cyclo-ligase
- MTBC0 PGAP product: 5-formyltetrahydrofolate cyclo-ligase
- Pfam (hmmscan --cut_ga): 5-FTHF_cyc-lig PF01812.27 (E=1e-50)
- (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_215507.1)
- Domains: Pfam-A via hmmscan --cut_ga — 5-FTHF_cyc-lig (PF01812.27)
- 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
COG0212 - Curated reference: UniProt O05575 (TrEMBL, unreviewed; 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 —
17 functional partner(s); context anchor
galU - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001063|Rv0992c| MAIASKSALRDQLLAARRRVADDVRAAEARMLRGHLERMVTSDSTVCAYVPVGGEPGSIEMLDVLLRRAGRVLLPVARTAGGDLPLPLRWGEYRAGGLARARWGLLEPPEPWLPEAALAQASLVLVPALAVDRQGVRLGRGRGFYDRSLRCRDPHARLVAVVRTVELVDVLPSEPHDVPMTHALTPERGLIALPCGE