Rv0446c Family assigned · medium auto-curated
H37Rv Rv0446c · MTBC0 mtbc0_000468 ·
256 aa · 537810–538580 (-) ·
RefSeq NP_214960.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF1295 domain-containing protein |
| Revised (this work) | DUF1295 domain-containing protein. Pfam: DUF1295 (PF06966.18), PEMT (PF04191.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53731
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible conserved transmembrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| eggNOG description | Protein of unknown function (DUF1295) |
| Orthologous group | COG2020 |
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) pseudogene candidate
| pN/pS | 1.468 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 10.27% of strains (14916) · clonal |
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 |
|---|---|---|---|---|
DUF1295 | PF06966.18 | 6.9e-81 | 17–243 | Protein of unknown function (DUF1295) |
PEMT | PF04191.19 | 2.9e-05 | 132–218 | Phospholipid methyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ufaA1 (cyclopropane-fatty-acyl-phospholipid synthase UfaA), high confidence from genomic context alone (score 946 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0449c hyp |
hypothetical protein | 982 | 983 ctx | neighborhood:803 fusion:635 cooccurence:763 |
Rv0448c hyp |
hypothetical protein | 971 | 972 ctx | neighborhood:882 cooccurence:767 |
Rv0447c ufaA1 |
cyclopropane-fatty-acyl-phospholipid synthase UfaA | 945 | 946 ctx | neighborhood:882 cooccurence:538 |
Rv0445c sigK |
ECF RNA polymerase sigma factor SigK | 763 | 763 ctx | neighborhood:694 |
Rv0444c rskA |
anti-sigma-K factor RskA | 673 | 673 ctx | neighborhood:593 |
Rv0450c mmpL4 |
transmembrane transport protein MmpL4 | 534 | 534 ctx | neighborhood:533 |
Rv0451c mmpS4 |
membrane protein MmpS4 | 509 | 510 ctx | neighborhood:508 |
Rv0885 hyp |
hypothetical protein | 478 | 150 | textmining:412 |
Rv3355c |
integral membrane protein | 657 | 55 | textmining:652 |
Rv1855c |
oxidoreductase | 643 | 50 | textmining:640 |
Rv3346c |
transmembrane protein | 614 | 47 | textmining:612 |
Rv3049c |
monooxygenase | 492 | 47 | textmining:489 |
Rv3675 |
membrane protein | 514 | 41 | textmining:514 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 431 | 41 | textmining:431 |
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: transmembrane protein
- MTBC0 PGAP product: DUF1295 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF1295 PF06966.18 (E=7e-81), PEMT PF04191.19 (E=3e-05)
- (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_214960.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF1295 (PF06966.18), PEMT (PF04191.19)
- 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
COG2020 - Curated reference: UniProt O53731 (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 —
14 functional partner(s); context anchor
ufaA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000468|Rv0446c| MVTSVSALAVAVVHSVAFAIGRRIGRYNVVDVVWGLGFVAVAVAAATLGHGDPVRRWLLLALVSTWGLRLSWHMYRKTAGQGEDPRYADLLRGATPVQALRKVFGLQGLLTLFVSFPLQLSAVTGPTPKPLLAVGGVGLAVWLVGITFEAVGDWQLWVFKSDPANRGVIMDRGLWAWTRHPNYFGDACVWWGLWLITINDWAPLATVGSPLLMTYLLVDVSGARLTERYLKGRPGFAEYQRRTAYFVPRPPRSARR