Rv2226 Family assigned · medium auto-curated
H37Rv Rv2226 · MTBC0 mtbc0_002364 ·
513 aa · 2524989–2526530 (+) ·
RefSeq NP_216742.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | CYTH and CHAD domain-containing protein |
| Revised (this work) | CYTH and CHAD domain-containing protein. Pfam: CYTH (PF01928.27), CHAD (PF05235.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WLH9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2226 |
UniProt still lists this protein as Uncharacterized protein Rv2226; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | CHAD |
| Orthologous group | COG3025 |
| Gene Ontology (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944
|
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 | 0.953 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
CYTH | PF01928.27 | 3.3e-12 | 12–138 | CYTH domain |
CHAD | PF05235.20 | 4.6e-45 | 238–462 | CHAD domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: panB (3-methyl-2-oxobutanoate hydroxymethyltransferase), high confidence from genomic context alone (score 730 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2225 panB |
3-methyl-2-oxobutanoate hydroxymethyltransferase | 730 | 730 ctx | neighborhood:726 |
Rv0210 hyp |
hypothetical protein | 533 | 534 ctx | cooccurence:531 |
Rv1619 hyp |
hypothetical protein | 510 | 511 ctx | cooccurence:497 |
Rv3689 |
transmembrane protein | 502 | 503 ctx | cooccurence:502 |
Rv2025c |
cation efflux system protein | 483 | 484 ctx | cooccurence:479 |
Rv1978 hyp |
hypothetical protein | 441 | 442 ctx | cooccurence:422 |
Rv3690 |
membrane protein | 462 | 441 ctx | cooccurence:412 |
Rv2319c |
universal stress protein | 438 | 438 ctx | cooccurence:421 |
Rv3691 hyp |
hypothetical protein | 453 | 432 ctx | cooccurence:401 |
Rv0345 hyp |
hypothetical protein | 418 | 418 ctx | cooccurence:418 |
Rv1265 hyp |
hypothetical protein | 416 | 416 ctx | cooccurence:416 |
Rv3055 |
TetR family transcriptional regulator | 400 | 401 | |
Rv1524 |
glycosyltransferase | 400 | 401 |
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: hypothetical protein
- MTBC0 PGAP product: CYTH and CHAD domain-containing protein
- Pfam (hmmscan --cut_ga): CYTH PF01928.27 (E=3e-12), CHAD PF05235.20 (E=5e-45)
- (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_216742.1)
- Domains: Pfam-A via hmmscan --cut_ga — CYTH (PF01928.27), CHAD (PF05235.20)
- 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
COG3025 - Curated reference: UniProt P9WLH9 (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 —
13 functional partner(s); context anchor
panB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002364|Rv2226| MPVEAPRPARHLEVERKFDVIESTVSPSFEGIAAVVRVEQSPTQQLDAVYFDTPSHDLARNQITLRRRTGGADAGWHLKLPAGPDKRTEMRAPLSASGDAVPAELLDVVLAIVRDQPVQPVARISTHRESQILYGAGGDALAEFCNDDVTAWSAGAFHAAGAADNGPAEQQWREWELELVTTDGTADTKLLDRLANRLLDAGAAPAGHGSKLARVLGATSPGELPNGPQPPADPVHRAVSEQVEQLLLWDRAVRADAYDAVHQMRVTTRKIRSLLTDSQESFGLKESAWVIDELRELANVLGVARDAEVLGDRYQRELDALAPELVRGRVRERLVDGARRRYQTGLRRSLIALRSQRYFRLLDALDALVSERAHATSGEESAPVTIDAAYRRVRKAAKAAKTAGDQAGDHHRDEALHLIRKRAKRLRYTAAATGADNVSQEAKVIQTLLGDHQDSVVSREHLIQQAIAANTAGEDTFTYGLLYQQEADLAERCREQLEAALRKLDKAVRKARD