lprN Family assigned · medium auto-curated
H37Rv Rv3495c · MTBC0 mtbc0_003710 ·
384 aa · 3937962–3939116 (-) ·
RefSeq NP_218012.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family lipoprotein LprN |
|---|---|
| MTBC0 PGAP re-annotation | Mce family lipoprotein LprN |
| Revised (this work) | Mce family lipoprotein LprN. Pfam: MlaD (PF02470.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y3P1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipoprotein LprN |
| Curated function | Stimulates the host (mouse) immune response; lipidated protein produced in E.coli stimulates T-cell proliferation in mice previously sensitized with LprN. Spleenocytes from these mice produce increased amounts of TNF and IFN-gamma, as well as somewhat increased nitric oxide levels, upon subsequent challenge with LprN. Previously sensitized mice infected with M.tuberculosis have an exacerbated disease response, suggesting this lipoprotein may down-regulate the host's immune response. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | lprN |
| eggNOG description | Virulence factor Mce family protein |
| Orthologous group | COG1463 |
| KEGG orthology |
K02067
|
| KEGG pathways |
map02010
|
| KEGG modules |
M00210, M00669, M00670
|
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 | 0.069 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
MlaD | PF02470.26 | 8.9e-14 | 41–121 | MlaD protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mce4D (Mce family protein Mce4D), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3496c mce4D |
Mce family protein Mce4D | 998 | 994 ctx | neighborhood:881 cooccurence:774 coexpression:804 textmining:821 |
Rv3497c mce4C |
Mce family protein Mce4C | 996 | 994 ctx | neighborhood:882 cooccurence:774 coexpression:785 textmining:512 |
Rv3498c mce4B |
Mce family protein Mce4B | 996 | 992 ctx | neighborhood:881 cooccurence:773 coexpression:732 textmining:596 |
Rv3494c mce4F |
Mce family protein Mce4 | 994 | 992 ctx | neighborhood:879 cooccurence:766 coexpression:730 |
Rv3500c yrbE4B |
integral membrane protein | 986 | 981 ctx | neighborhood:859 cooccurence:770 |
Rv3492c |
Mce associated protein | 978 | 978 ctx | neighborhood:879 cooccurence:755 |
Rv3501c yrbE4A |
integral membrane protein | 979 | 973 ctx | neighborhood:815 cooccurence:759 |
Rv3499c mce4A |
Mce family protein Mce4A | 978 | 973 ctx | neighborhood:881 cooccurence:774 |
Rv3493c |
Mce associated protein | 900 | 901 ctx | neighborhood:879 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 910 | 882 ctx | cooccurence:753 experimental:431 |
Rv0168 yrbE1B |
membrane protein | 877 | 870 ctx | cooccurence:766 |
Rv0588 yrbE2B hyp |
hypothetical protein | 875 | 868 ctx | cooccurence:765 |
Rv1965 yrbE3B |
integral membrane protein | 874 | 867 ctx | cooccurence:763 |
Rv0167 yrbE1A |
membrane protein | 867 | 862 ctx | cooccurence:752 |
Rv1964 yrbE3A |
integral membrane protein | 874 | 859 ctx | cooccurence:743 |
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: Mce family lipoprotein LprN
- MTBC0 PGAP product: Mce family lipoprotein LprN
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=9e-14)
- (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_218012.1)
- Domains: Pfam-A via hmmscan --cut_ga — MlaD (PF02470.26)
- 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
COG1463 - Curated reference: UniProt I6Y3P1 (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 —
52 functional partner(s); context anchor
mce4D - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003710|Rv3495c|lprN MNRIWLRAIILTASSALLAGCQFGGLNSLPLPGTAGHGEGAYSVTVEMADVATLPQNSPVMVDDVTVGSVAGIVAVQRPDGSFYAAVKLDLDKNVLLPANAVAKVSQTSLLGSLHVELAPPTDRPPTGRLVDGSRITEANTDRFPTTEEVFSALGVVVNKGNVGALEEIIDETHQAVAGRQAQFVNLVPRLAELTAGLNRQVHDIIDALDGLNRVSAILARDKDNLGRALDTLPDAVRVLNQNRDHIVDAFAALKRLTMVTSHVLAETKVDFGEDLKDLYSIVKALNDDRKDFVTSLQLLLTFPFPNFGIKQAVRGDYLNVFTTFDLTLRRIGETFFTTAYFDPNMAHMDEILNPPDFLIGELANLSGQAADPFKIPPGTASGQ