Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | SPFH domain-containing protein |
|---|
| Revised (this work) | SPFH domain-containing protein. Pfam: Band_7 (PF01145.32). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05769
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Protease Rv3090 |
|---|
| EC (curated) |
EC 3.4.-.-
|
|---|
| Curated function | Protease that triggers late cell apoptosis and contributes to the pathogenicity and dissemination of M.tuberculosis. In a mouse model of infection, can induce hepatocyte and lung cell apoptosis and cause pathological damage to the spleen, liver and lungs. Specifically stimulates the secretion of inflammatory cytokines including TNF, IL-6 and IL-1 beta. Can degrade casein in vitro. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|
| eggNOG description | SPFH domain / Band 7 family |
|---|
| Orthologous group | COG0330 |
|---|
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 |
2.566 · diversifying/relaxed
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 8 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 |
|---|
Band_7 | PF01145.32 |
2.5e-23 | 56–245 |
SPFH domain / Band 7 family |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3610c ftsH |
zinc metalloprotease FtsH |
956 |
951 |
experimental:805 database:633 |
Rv2782c pepR |
zinc protease |
776 |
749 |
database:594 |
Rv3091 hyp |
hypothetical protein |
732 |
732 ctx |
neighborhood:732 |
Rv0110 |
integral membrane protein |
697 |
670 |
database:619 |
Rv1337 |
integral membrane protein |
697 |
670 |
database:619 |
Rv2124c metH |
methionine synthase |
661 |
648 |
database:591 |
Rv1819c bacA |
vitamin B12 transport ATP-binding protein BacA |
632 |
623 |
database:581 |
Rv1389 gmk |
guanylate kinase |
629 |
613 |
database:556 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase |
621 |
596 |
database:530 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA |
611 |
595 |
database:537 |
Rv0435c |
ATPase |
611 |
595 |
database:537 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA |
611 |
595 |
database:537 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 |
611 |
595 |
database:537 |
Rv2443 dctA |
C4-dicarboxylate-transport transmembrane protein DctA |
625 |
592 |
database:533 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase |
590 |
590 |
database:530 |
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: SPFH domain-containing protein
- Pfam (hmmscan --cut_ga): Band_7 PF01145.32 (E=3e-23)
- (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_217606.1)
- Domains: Pfam-A via hmmscan --cut_ga — Band_7 (PF01145.32)
- 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
COG0330
- Curated reference: UniProt
O05769
(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 —
46 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003284|Rv3090|
MTWQIVFVVICVIVAGVAALFWRLPSDDTTRSRAKTVTIAAVAAAAVFFFLGCFTIVGTRQFAIMTTFGRPTGVSLNNGFHGKWPWQMTHPMDGAVQIDKYVKEGNTDQRITVRLGNQSTALADVSIRWQLKQAAAPELFQQYKTFDNVRVNLIERNLSVALNEVFAGFNPLDPRNLDVSPLPSLAKRAADILRQDVGGQVDIFDVNVPTIQYDQSTEDKINQLNQQRAQTSIALEAQRTAEAQAKANEILSRSISDDPNVVVQNCITAAINKGISPLGCWPGSSALPTIAVPGR
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