lppW Family assigned · medium
H37Rv Rv2905 · MTBC0 mtbc0_003087 ·
314 aa · 3235457–3236401 (+) ·
RefSeq NP_217421.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppW |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Serine-hydrolase of the class A beta-lactamase / penicillin-binding fold. RefSeq leaves it 'lipoprotein LppW'. Two independent signals converge: eggNOG annotates a 'Beta-lactamase' orthologous group (COG V, defense), and the AlphaFold model superposes on the class A beta-lactamase PenL (PDB 5gld; Foldseek prob 1.0, E 8e-10, TM 0.71). A locus distinct from the canonical M. tuberculosis beta-lactamase BlaC (Rv2068c); the Ser-x-x-Lys catalytic motif and the substrate are not demonstrated here. |
Curated reference (UniProt)
| UniProt |
P9WK67
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative lipoprotein LppW |
UniProt still lists this protein as Putative lipoprotein LppW; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| Preferred name | lppW |
| eggNOG description | Beta-lactamase |
| Orthologous group | COG2367 |
| Gene Ontology (2) |
GO:0005575, GO:0005576
|
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 | 0.287 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 4 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccD3 (ESX-3 secretion system protein EccD), medium confidence from genomic context alone (score 638 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1836c hyp |
hypothetical protein | 698 | 698 ctx | cooccurence:683 |
Rv3906c hyp |
hypothetical protein | 684 | 685 ctx | cooccurence:666 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 637 | 638 ctx | cooccurence:636 |
Rv1698 mctB |
copper transporter MctB | 623 | 624 ctx | cooccurence:618 |
Rv0518 hyp |
hypothetical protein | 592 | 593 ctx | cooccurence:588 |
Rv0990c hyp |
hypothetical protein | 555 | 556 ctx | cooccurence:554 |
Rv0472c |
HTH-type transcriptional regulator | 550 | 551 ctx | cooccurence:544 |
Rv0499 hyp |
hypothetical protein | 547 | 548 ctx | cooccurence:526 |
Rv1118c hyp |
hypothetical protein | 520 | 521 ctx | cooccurence:518 |
Rv1639c hyp |
hypothetical protein | 521 | 519 ctx | cooccurence:504 |
Rv3587c |
membrane protein | 514 | 515 ctx | cooccurence:508 |
Rv3810 pirG |
cell surface protein | 512 | 512 ctx | cooccurence:507 |
Rv2091c |
membrane protein | 508 | 508 ctx | cooccurence:503 |
Rv0517 |
acyltransferase | 501 | 501 ctx | cooccurence:501 |
Rv0010c |
membrane protein | 496 | 497 ctx | cooccurence:492 |
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
- eggNOG OG 'Beta-lactamase', COG V (defense)
- Foldseek -> class A beta-lactamase PenL (5gld), prob 1.0, E 8e-10, TM 0.71
- Distinct locus from BlaC/Rv2068c (fold-paralogue safeguard)
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_217421.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG2367 - Curated reference: UniProt P9WK67 (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
eccD3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003087|Rv2905|lppW MRARPLTLLTALAAVTLVVVAGCEARVEAEAYSAADRISSRPQARPQPQPVELLLRAITPPRAPAASPNVGFGELPTRVRQATDEAAAMGATLSVAVLDRATGQLVSNGNTQIIATASVAKLFIADDLLLAEAEGKVTLSPEDHHALDVMLQSSDDGAAERFWSQDGGNAVVTQVARRYGLRSTAPPSDGRWWNTISSAPDLIRYYDMLLDGSGGLPLDRAAVIIADLAQSTPTGIDGYPQRFGIPDGLYAEPVAVKQGWMCCIGSSWMHLSTGVIGPERRYIMVIESLQPADDATARATITQAVRTMFPNGRI