Rv3626c Resolved · high auto-curated
H37Rv Rv3626c · MTBC0 mtbc0_003843 ·
350 aa · 4088555–4089607 (-) ·
RefSeq NP_218143.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | zinc-dependent metalloprotease |
| Revised (this work) | Zinc-dependent metalloprotease. Pfam: Zincin_2 (PF10103.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06381
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Zincin-like metallopeptidase |
| Orthologous group | COG5282 |
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 | 0.845 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 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 |
|---|---|---|---|---|
Zincin_2 | PF10103.16 | 1.2e-93 | 13–346 | Zincin-like metallopeptidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mesJ (tRNA(Ile)-lysidine synthase), high confidence from genomic context alone (score 888 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) |
|---|---|---|---|---|
Rv3627c dacB hyp |
hypothetical protein | 991 | 922 ctx | neighborhood:882 textmining:896 |
Rv3625c mesJ |
tRNA(Ile)-lysidine synthase | 984 | 888 ctx | neighborhood:881 textmining:870 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 982 | 882 ctx | neighborhood:881 textmining:860 |
Rv3628 ppa |
inorganic pyrophosphatase | 775 | 775 ctx | neighborhood:774 |
Rv2867c |
GCN5-like N-acetyltransferase | 701 | 701 ctx | cooccurence:697 |
Rv2239c hyp |
hypothetical protein | 609 | 610 ctx | cooccurence:585 |
Rv0472c |
HTH-type transcriptional regulator | 541 | 542 ctx | cooccurence:537 |
Rv2097c pafA |
proteasome accessory factor PafA | 508 | 508 ctx | cooccurence:501 |
Rv0051 |
transmembrane protein | 482 | 482 ctx | cooccurence:477 |
Rv2112c dop |
pup deamidase/depupylase | 478 | 479 ctx | cooccurence:471 |
Rv3015c hyp |
hypothetical protein | 450 | 451 ctx | cooccurence:449 |
Rv3780 bpa hyp |
hypothetical protein | 433 | 434 ctx | cooccurence:431 |
Rv1457c |
antibiotic ABC transporter permease | 433 | 434 ctx | cooccurence:426 |
Rv3601c panD |
aspartate 1-decarboxylase | 444 | 98 | textmining:410 |
Rv2852c mqo |
malate:quinone oxidoreductase | 810 | 70 | textmining:805 |
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: zinc-dependent metalloprotease
- Pfam (hmmscan --cut_ga): Zincin_2 PF10103.16 (E=1e-93)
- (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_218143.1)
- Domains: Pfam-A via hmmscan --cut_ga — Zincin_2 (PF10103.16)
- 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
COG5282 - Curated reference: UniProt O06381 (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 —
21 functional partner(s); context anchor
mesJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003843|Rv3626c| MTGASELTLGNTVDWEFAASVGERLARPAPPSTEYTRRQVIDELTVAAEKAEPPVRDVTGLIADGVVPPARVVDRPAWIRSAAESMRAMTHGSAKPRGFLTGRITGAQTGAVLAFVASGILGQYDPFGAAGEGCLLLVYPNVIAVERQLRVEPSDFRLWVCLHEVTHRVQFTANPWLSGYMSQALNLLTFEPVDDIGRVVSRLADFIRSRGHGTDDSEVNPSGILGLVRAVQSEPQRKALDQLLVLGTLLEGHAEHVMDAVGPMVVPSVATIRRRFDDRRHHKQPPLQRLVRALLGFDAKLSQYTRGKAFVDHVVDRAGMKLFNTIWSGPETLPLPAEIENPQRWIDRVL