Rv2230c Resolved · medium auto-curated
H37Rv Rv2230c · MTBC0 mtbc0_002369 ·
379 aa · 2529627–2530766 (-) ·
RefSeq NP_216746.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GTP cyclohydrolase |
|---|---|
| MTBC0 PGAP re-annotation | Nif3-like dinuclear metal center hexameric protein |
| Revised (this work) | Nif3-like dinuclear metal center hexameric protein. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFM1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GTP cyclohydrolase 1 type 2 homolog |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the GTP cyclohydrolase I type 2 NIF3 family |
| Orthologous group | COG0327 |
| Gene Ontology (6) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0044424, GO:0044464
|
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 | 0.613 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
DUF34_NIF3 | PF01784.25 | 8.2e-60 | 4–364 | Duf34/NIF3 (NGG1p interacting factor 3) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobC (aminotransferase), high confidence from genomic context alone (score 976 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2231c cobC |
aminotransferase | 996 | 976 ctx | neighborhood:882 coexpression:805 textmining:870 |
Rv2229c hyp |
hypothetical protein | 994 | 923 ctx | neighborhood:882 textmining:929 |
Rv2228c |
multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase | 990 | 919 ctx | neighborhood:892 textmining:882 |
Rv2234 ptpA |
protein-tyrosine-phosphatase | 766 | 758 ctx | neighborhood:746 |
Rv2235 |
transmembrane protein | 749 | 750 ctx | neighborhood:746 |
Rv2232 ptkA |
protein tyrosine kinase transcriptional regulator PtkA | 747 | 748 ctx | neighborhood:746 |
Rv2231A vapC16 |
ribonuclease VapC16 | 658 | 658 ctx | neighborhood:658 |
Rv1629 polA |
DNA polymerase I | 619 | 620 ctx | neighborhood:544 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 554 | 555 ctx | neighborhood:544 |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 547 | 548 ctx | neighborhood:544 |
Rv3722c hyp |
hypothetical protein | 510 | 511 | coexpression:507 |
Rv2343c dnaG |
DNA primase | 522 | 492 | |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 457 | 458 | coexpression:427 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 455 | 456 | coexpression:425 |
Rv0264c hyp |
hypothetical protein | 463 | 440 | coexpression:421 |
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: GTP cyclohydrolase
- MTBC0 PGAP product: Nif3-like dinuclear metal center hexameric protein
- Pfam (hmmscan --cut_ga): DUF34_NIF3 PF01784.25 (E=8e-60)
- (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_216746.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF34_NIF3 (PF01784.25)
- 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
COG0327 - Curated reference: UniProt P9WFM1 (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 —
35 functional partner(s); context anchor
cobC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002369|Rv2230c| MSVRLADVIDVLDQAYPPRLAQSWDSVGLVCGDPDDVVDSVTVAVDATPAVVDQVPQAGLLLVHHPLLLRGVDTVAANTPKGVLVHRLIRTGRSLFTAHTNADSASPGVSDALAHAVGLTVDAVLDPVPGAADLDKWVIYVPRENSEAVRAAVFEAGAGHIGDYSHCSWSVAGTGQFLAHDGASPAIGSVGTVERVAEDRVEVVAPARARAEVLAAMRAAHPYEEPAFDIFALVPPPVGSGLGRIGRLPKPEPLRTFVARLEAALPPTATGVRAAGDPDLLVSRVAVCGGAGDSLLATVAAADVQAYVTADLRHHPADEHCRASQVALIDVAHWASEFPWCGQAAEVLRSHFGASLPVRVCTICTDPWNLDHETGRDQA