Rv2625c Family assigned · medium auto-curated
H37Rv Rv2625c · MTBC0 mtbc0_002794 ·
393 aa · 2974884–2976065 (-) ·
RefSeq NP_217141.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | zinc metalloprotease Rip3 |
|---|---|
| MTBC0 PGAP re-annotation | site-2 protease family protein |
| Revised (this work) | Site-2 protease family protein. Pfam: Peptidase_M50 (PF02163.29), CBS (PF00571.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHR1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative zinc metalloprotease Rip3 |
UniProt still lists this protein as Putative zinc metalloprotease Rip3; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the peptidase M50B family |
| Orthologous group | COG0517 |
| Gene Ontology (14) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226, GO:0044425, GO:0044459 +2 more
|
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 | 1.131 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
Peptidase_M50 | PF02163.29 | 2.9e-12 | 56–132 | Peptidase family M50 |
CBS | PF00571.34 | 4.8e-04 | 311–367 | CBS domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2624c (universal stress protein), high confidence from genomic context alone (score 971 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2624c |
universal stress protein | 975 | 971 ctx | neighborhood:748 coexpression:857 |
Rv2626c hrp1 |
hypoxic response protein | 920 | 920 ctx | neighborhood:609 coexpression:805 |
Rv2030c hyp |
hypothetical protein | 949 | 913 ctx | cooccurence:498 coexpression:831 textmining:441 |
Rv1997 ctpF |
cation transporter ATPase F | 924 | 908 | coexpression:876 |
Rv2028c |
universal stress protein | 902 | 882 | coexpression:860 |
Rv2029c pfkB |
6-phosphofructokinase PfkB | 880 | 866 | coexpression:860 |
Rv2623 TB31.7 |
universal stress protein | 878 | 862 | coexpression:803 |
Rv1736c narX |
nitrate reductase-like protein NarX | 860 | 860 | coexpression:860 |
Rv2032 acg |
NAD(P)H nitroreductase | 878 | 835 | coexpression:803 |
Rv1733c |
transmembrane protein | 832 | 833 | coexpression:810 |
Rv2627c hyp |
hypothetical protein | 830 | 831 | coexpression:806 |
Rv1737c narK2 |
nitrate/nitrite transporter | 842 | 810 | coexpression:805 |
Rv3134c |
universal stress protein | 820 | 800 | coexpression:751 |
Rv3128c |
Rv3128c, (MTCY164.38c), len: 337 aa. Conserved hypothetical protein, similar to other conserved hypothetical proteins. This ORF corresponds | 899 | 799 | coexpression:799 textmining:519 |
Rv2628 hyp |
hypothetical protein | 797 | 797 | coexpression:797 |
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: zinc metalloprotease Rip3
- MTBC0 PGAP product: site-2 protease family protein
- Pfam (hmmscan --cut_ga): Peptidase_M50 PF02163.29 (E=3e-12), CBS PF00571.34 (E=5e-04)
- (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_217141.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M50 (PF02163.29), CBS (PF00571.34)
- 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
COG0517 - Curated reference: UniProt P9WHR1 (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 —
40 functional partner(s); context anchor
Rv2624c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002794|Rv2625c| MRDAIPLGRIAGFVVNVHWSVLVILWLFTWSLATMLPGTVGGYPAVVYWLLGAGGAVMLLASLLAHELAHAVVARRAGVSVESVTLWLFGGVTALGGEAKTPKAAFRIAFAGPATSLALSATFGALAITLAGVRTPAIVISVAWWLATVNLLLGLFNLLPGAPLDGGRLVRAYLWRRHGDSVRAGIGAARAGRVVALVLIALGLAEFVAGGLVGGVWLAFIGWFIFAAAREEETRISTQQLFAGVRVADAMTAQPHTAPGWINVEDFIQRYVLGERHSAYPVADRDGSITGLVALRQLRDVAPSRRSTTSVGDIALPLHSVPTARPQEPLTALLERMAPLGPRSRALVTEGSAVVGIVTPSDVARLIDVYRLAQPEPTFTTSPQDADRFSDAG