lppH Resolved · high auto-curated
H37Rv Rv3576 · MTBC0 - ·
237 aa · 4018358–4019071 (+) ·
RefSeq YP_177991.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppH |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Lipoprotein LppH. Pfam: PknH_C (PF14032.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
I6YGJ4
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible conserved lipoprotein LppH |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K TranscriptionL Replication, recombination and repairT Signal transduction mechanisms
|
|---|---|
| Preferred name | lppH |
| eggNOG description | PknH-like extracellular domain |
| Orthologous group | COG0515 |
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 | 2.411 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 8 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.60% of strains (871) · 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 |
|---|---|---|---|---|
PknH_C | PF14032.13 | 5.2e-60 | 44–233 | PknH-like extracellular domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: arsB2 (arsenic transport integral membrane protein ArsB), medium confidence from genomic context alone (score 583 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3577 hyp |
hypothetical protein | 746 | 746 ctx | neighborhood:738 |
Rv3578 arsB2 |
arsenic transport integral membrane protein ArsB | 584 | 583 ctx | neighborhood:581 |
Rv3575c |
LacI family transcriptional regulator | 583 | 562 ctx | neighborhood:562 |
Rv2060 |
integral membrane protein | 538 | 538 ctx | neighborhood:538 |
Rv2059 hyp |
hypothetical protein | 550 | 532 ctx | neighborhood:531 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 460 | 388 | |
Rv2339 mmpL9 |
transmembrane transport protein MmpL9 | 581 | 172 | textmining:515 |
Rv2116 lppK |
lipoprotein LppK | 709 | 83 | textmining:697 |
Rv3759c proX |
glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX | 523 | 80 | textmining:503 |
Rv0835 lpqQ |
lipoprotein LpqQ | 630 | 65 | textmining:621 |
Rv1274 lprB |
lipoprotein LprB | 610 | 63 | textmining:602 |
Rv1275 lprC |
lipoprotein LprC | 523 | 62 | textmining:513 |
Rv2291 sseB |
thiosulfate sulfurtransferase SseB | 525 | 56 | textmining:518 |
Rv2138 lppL |
lipoprotein LppL | 436 | 53 | textmining:429 |
Rv1857 modA |
molybdate ABC transporter substrate-binding lipoprotein ModA | 409 | 53 | textmining:402 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): lipoprotein LppH
- Pfam (hmmscan --cut_ga): PknH_C PF14032.13 (E=5e-60)
- (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 YP_177991.1)
- Domains: Pfam-A via hmmscan --cut_ga — PknH_C (PF14032.13)
- 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
COG0515 - Curated reference: UniProt I6YGJ4 (TrEMBL, unreviewed; 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 —
38 functional partner(s); context anchor
arsB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3576|lppH MGKQLAALAALVGACMLAAGCTNVVDGTAVAADKSGPLHQDPIPVSALEGLLLDLSQINAALGATSMKVWFNAKAMWDWSKSVADKNCLAIDGPAQEKVYAGTGWTAMRGQRLDDSIDDSKKRDHYAIQAVVGFPTAHDAEEFYSSSVQSWSSCSNRRFVEVTPGQDDAAWTVADVVNDNGMLSSSQVQEGGDGWTCQRALTARNNVTIDIVTCAYSQPDLVAIGIANQIAAKVAKQ