Rv2446c Still unknown · low auto-curated
H37Rv Rv2446c · MTBC0 mtbc0_002605 ·
123 aa · 2770015–2770386 (-) ·
RefSeq NP_216962.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4233 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF4233. Function unknown. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53173
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Probable conserved integral membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF4233) |
| Orthologous group | 2DAVQ |
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 | 0.198 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
DUF4233 | PF14017.12 | 7.9e-33 | 18–117 | Protein of unknown function (DUF4233) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folC (folylpolyglutamate synthase FolC), high confidence from genomic context alone (score 909 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2447c folC |
folylpolyglutamate synthase FolC | 967 | 909 ctx | neighborhood:882 textmining:660 |
Rv2448c valS |
valine--tRNA ligase | 940 | 904 ctx | neighborhood:881 textmining:406 |
Rv0556 |
transmembrane protein | 778 | 778 ctx | cooccurence:774 |
Rv2732c |
transmembrane protein | 777 | 777 ctx | cooccurence:772 |
Rv3205c hyp |
hypothetical protein | 776 | 776 ctx | cooccurence:773 |
Rv0863 hyp |
hypothetical protein | 775 | 775 ctx | cooccurence:774 |
Rv3212 hyp |
hypothetical protein | 775 | 775 ctx | cooccurence:772 |
Rv3438 hyp |
hypothetical protein | 774 | 775 ctx | cooccurence:774 |
Rv0358 hyp |
hypothetical protein | 774 | 774 ctx | cooccurence:774 |
Rv1109c hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:772 |
Rv3311 hyp |
hypothetical protein | 772 | 772 ctx | cooccurence:771 |
Rv3850 hyp |
hypothetical protein | 772 | 772 ctx | cooccurence:771 |
Rv3217c |
integral membrane protein | 769 | 769 ctx | cooccurence:766 |
Rv0996 |
transmembrane protein | 766 | 767 ctx | cooccurence:766 |
Rv1083 hyp |
hypothetical protein | 763 | 763 ctx | cooccurence:763 |
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: integral membrane protein
- MTBC0 PGAP product: DUF4233 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF4233 PF14017.12 (E=8e-33)
- (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_216962.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4233 (PF14017.12)
- 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
2DAVQ - Curated reference: UniProt O53173 (TrEMBL, unreviewed; Predicted)
- 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 —
116 functional partner(s); context anchor
folC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002605|Rv2446c| MTDRSREPADPWKGFSAVMAATLILEAIVVLLAIPVVDAVGGGLRPASLGYLVGLAVLLILLTGLQRRPWAIWVNLGAQPVLVAGFAVYPGVGFIGVLFAALWVLIAYLRAEVRRRRDYRVSQ