lepB Resolved · high auto-curated
H37Rv Rv2903c · MTBC0 mtbc0_003085 ·
294 aa · 3233799–3234683 (-) ·
RefSeq NP_217419.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | signal peptidase |
|---|---|
| MTBC0 PGAP re-annotation | signal peptidase I |
| Revised (this work) | Signal peptidase I. Pfam: Peptidase_S26 (PF10502.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Signal peptidase I |
| EC (curated) |
EC 3.4.21.89
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
U Intracellular trafficking, secretion and vesicular transport
|
|---|---|
| Preferred name | lepB |
| eggNOG description | Belongs to the peptidase S26 family |
| Orthologous group | COG0681 |
| EC number |
EC 3.4.21.89
|
| KEGG orthology |
K03100
|
| KEGG pathways |
map02024, map03060
|
| Gene Ontology (15) |
GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0040007, GO:0044425 +3 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 | 0.115 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 |
|---|---|---|---|---|
Peptidase_S26 | PF10502.15 | 4.4e-44 | 66–277 | Signal peptidase, peptidase S26 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rnhB (ribonuclease HII), high confidence from genomic context alone (score 975 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2902c rnhB |
ribonuclease HII | 975 | 975 ctx | neighborhood:872 coexpression:813 |
Rv2904c rplS |
50S ribosomal protein L19 | 846 | 847 ctx | neighborhood:805 |
Rv2901c hyp |
hypothetical protein | 812 | 812 ctx | neighborhood:802 |
Rv1305 atpE |
ATP synthase subunit C | 703 | 670 | database:647 |
Rv0722 rpmD |
50S ribosomal protein L30 | 676 | 663 | database:588 |
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD | 664 | 648 | database:626 |
Rv3062 ligB |
DNA ligase | 656 | 640 | database:626 |
Rv3731 ligC |
DNA ligase C | 654 | 638 | database:626 |
Rv2404c lepA |
GTP-binding protein LepA | 843 | 634 | coexpression:557 textmining:590 |
Rv2869c rip |
zinc metalloprotease | 610 | 574 | coexpression:412 |
Rv2992c gltS |
glutamate--tRNA ligase | 557 | 535 | |
Rv3921c yidC |
membrane protein insertase YidC | 639 | 529 | coexpression:408 |
Rv2733c miaB |
(dimethylallyl)adenosine tRNA methylthiotransferase | 518 | 518 | coexpression:418 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 517 | 517 | database:501 |
Rv2444c rne |
ribonuclease E | 516 | 517 | coexpression:439 |
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: signal peptidase
- MTBC0 PGAP product: signal peptidase I
- Pfam (hmmscan --cut_ga): Peptidase_S26 PF10502.15 (E=4e-44)
- (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_217419.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S26 (PF10502.15)
- 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
COG0681 - Curated reference: UniProt P9WKA1 (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 —
95 functional partner(s); context anchor
rnhB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003085|Rv2903c|lepB MTETTDSPSERQPGPAEPELSSRDPDIAGQVFDAAPFDAAPDADSEGDSKAAKTDEPRPAKRSTLREFAVLAVIAVVLYYVMLTFVARPYLIPSESMEPTLHGCSTCVGDRIMVDKLSYRFGSPQPGDVIVFRGPPSWNVGYKSIRSHNVAVRWVQNALSFIGFVPPDENDLVKRVIAVGGQTVQCRSDTGLTVNGRPLKEPYLDPATMMADPSIYPCLGSEFGPVTVPPGRVWVMGDNRTHSADSRAHCPLLCTDDPLPGTVPVANVIGKARLIVWPPSRWGVVRSVNPQQGR