Rv3364c Resolved · high auto-curated
H37Rv Rv3364c · MTBC0 mtbc0_003579 ·
130 aa · 3801190–3801582 (-) ·
RefSeq NP_217881.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | serine protease inhibitor |
| Revised (this work) | Serine protease inhibitor. Pfam: Robl_LC7 (PF03259.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50393
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine protease inhibitor Rv3364c |
| Curated function | Effector protein that binds to the host serine protease cathepsin G on the macrophage cell membrane, inhibiting its enzymatic activity and the downstream activation of caspase-1-dependent apoptosis. Thus prevents macrophage pyroptosis and helps M.tuberculosis survival within host cells. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PFAM Roadblock LC7 |
| Orthologous group | COG2018 |
| KEGG orthology |
K07131
|
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 | 0.723 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
Robl_LC7 | PF03259.24 | 2.3e-24 | 10–101 | Roadblock/LC7 domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3362c (ATP/GTP-binding protein), high confidence from genomic context alone (score 1000 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) |
|---|---|---|---|---|
Rv3362c |
ATP/GTP-binding protein | 999 | 1000 ctx | neighborhood:882 cooccurence:774 coexpression:807 experimental:917 textmining:838 |
Rv3363c hyp |
hypothetical protein | 997 | 984 ctx | neighborhood:882 cooccurence:774 coexpression:458 textmining:870 |
Rv3365c hyp |
hypothetical protein | 994 | 973 ctx | neighborhood:882 cooccurence:769 textmining:810 |
Rv3361c mfpA hyp |
hypothetical protein | 984 | 887 ctx | neighborhood:882 textmining:870 |
Rv3366 spoU |
tRNA/rRNA methylase SpoU | 493 | 492 ctx | neighborhood:486 |
Rv0585c |
integral membrane protein | 452 | 453 ctx | cooccurence:451 |
Rv0923c hyp |
hypothetical protein | 429 | 429 ctx | cooccurence:423 |
Rv0047c hyp |
hypothetical protein | 422 | 422 ctx | cooccurence:421 |
Rv2068c blaC |
beta-lactamase | 706 | 195 | textmining:651 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 582 | 179 | textmining:513 |
Rv3671c marP |
serine protease | 640 | 83 | textmining:624 |
Rv3654c hyp |
hypothetical protein | 659 | 45 | textmining:658 |
Rv0198c zmp1 |
zinc metalloprotease | 521 | 44 | textmining:520 |
Rv3354 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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: serine protease inhibitor
- Pfam (hmmscan --cut_ga): Robl_LC7 PF03259.24 (E=2e-24)
- (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_217881.1)
- Domains: Pfam-A via hmmscan --cut_ga — Robl_LC7 (PF03259.24)
- 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
COG2018 - Curated reference: UniProt O50393 (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 —
14 functional partner(s); context anchor
Rv3362c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003579|Rv3364c| MKARLPDSPLDWLVSKFAREVPGVAHALLVSVDGLPVAASEHLPRERADQLAAVTSGLASLAGGAAQLFDGGQVLQSVVEMQNGYLLLMQVGDGSALAALAATGCDIGQIGYEMAILVERVGGVVQSCRR