Rv1842c Family assigned · medium auto-curated
H37Rv Rv1842c · MTBC0 mtbc0_001955 ·
455 aa · 2108762–2110129 (-) ·
RefSeq NP_216358.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hemolysin family protein |
| Revised (this work) | Hemolysin family protein. Pfam: CNNM (PF01595.26), CBS (PF00571.34), CorC_HlyC (PF03471.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFP3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | UPF0053 protein Rv1842c |
UniProt still lists this protein as UPF0053 protein Rv1842c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | tlyC |
| eggNOG description | Hemolysins and related proteins containing CBS domains |
| Orthologous group | COG1253 |
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 | 0.841 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (160) · 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 |
|---|---|---|---|---|
CNNM | PF01595.26 | 9.6e-38 | 12–203 | Cyclin M transmembrane N-terminal domain |
CBS | PF00571.34 | 2.6e-04 | 221–276 | CBS domain |
CorC_HlyC | PF03471.23 | 2.8e-16 | 357–441 | Transporter associated domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: guaB1 (inosine-5'-monophosphate dehydrogenase), high confidence from genomic context alone (score 808 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) |
|---|---|---|---|---|
Rv1841c hyp |
hypothetical protein | 981 | 981 ctx | neighborhood:882 coexpression:801 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 815 | 808 ctx | neighborhood:743 |
Rv1844c gnd1 |
6-phosphogluconate dehydrogenase | 731 | 732 ctx | neighborhood:719 |
Rv1845c blaR |
sensor-transducer protein BlaR | 716 | 716 ctx | neighborhood:700 |
Rv1846c blaI |
transcriptional repressor BlaI | 699 | 699 ctx | neighborhood:695 |
Rv1837c glcB |
malate synthase | 641 | 642 ctx | neighborhood:639 |
Rv1836c hyp |
hypothetical protein | 626 | 627 ctx | neighborhood:618 |
Rv1840c PE_PGRS34 |
PE-PGRS family protein PE_PGRS34 | 504 | 485 ctx | neighborhood:485 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 417 | 418 | |
Rv2367c ybeY |
endoribonuclease | 422 | 396 | |
Rv3396c guaA |
GMP synthase | 418 | 191 |
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: hemolysin family protein
- Pfam (hmmscan --cut_ga): CNNM PF01595.26 (E=1e-37), CBS PF00571.34 (E=3e-04), CorC_HlyC PF03471.23 (E=3e-16)
- (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_216358.1)
- Domains: Pfam-A via hmmscan --cut_ga — CNNM (PF01595.26), CBS (PF00571.34), CorC_HlyC (PF03471.23)
- 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
COG1253 - Curated reference: UniProt P9WFP3 (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 —
11 functional partner(s); context anchor
guaB1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001955|Rv1842c| MNLTDTVATILAILALTAGTGVFVAAEFSLTALDRSTVEANARGGTSRDRFIQRAHHRLSFQLSGAQLGISITTLATGYLTEPLVAELPHPGLVAVGMSDRVADGLITFFALVIVTSLSMVFGELVPKYLAVARPLRTARSVVAGQVLFSLLLTPAIRLTNGAANWIVRRLGIEPAEELRSARTPQELVSLVRSSARSGALDDATAWLMRRSLQFGALTAEELMTPRSKIVALQTDDTIADLVAAAAASGFSRFPVVEGDLDATVGIVHVKQVFEVPPGDRAHTLLTTVAEPVAVVPSTLDGDAVMAQVRASALQTAMVVDEYGGTAGMVTLEDLIEEIVGDVRDEHDDATPDVVAAGNGWRVSGLLRIDEVASATGYRAPDGPYETIGGLVLRELGHIPVAGETVELTALDQDGLPDDSMRWLATVIQMDGRRIDLLELIKMGGHADPGSGRGR