lppY Still unknown · low auto-curated

H37Rv Rv2999 · MTBC0 mtbc0_003188 · 321 aa · 3378911–3379876 (+) · RefSeq NP_217515.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipoprotein LppY
MTBC0 PGAP re-annotationDUF1259 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF1529. Function unknown.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O53246 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved lipoprotein LppY

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namelpqO
eggNOG descriptionDomain of Unknown Function (DUF1259)
Orthologous groupCOG1388

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 0.688 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (159) · 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)

PfamAccessioni-EvalueResiduesDescription
DUF1529PF07485.17 1.0e-4153–174 Domain of Unknown Function (DUF1259)

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv3000 (transmembrane protein), medium confidence from genomic context alone (score 681 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3000 transmembrane protein 681 681 ctx neighborhood:634
Rv2998A Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens 518 518 ctx neighborhood:518
Rv2954c hyp hypothetical protein 466 466 ctx cooccurence:466
Rv2275 cyclo(L-tyrosyl-L-tyrosyl) synthase 426 427 ctx cooccurence:423
Rv3727 oxidoreductase 402 402 ctx cooccurence: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

  • Legacy H37Rv annotation: lipoprotein LppY
  • MTBC0 PGAP product: DUF1259 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF1529 PF07485.17 (E=1e-41)
  • (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_217515.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF1529 (PF07485.17)
  • 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 COG1388
  • Curated reference: UniProt O53246 (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 — 5 functional partner(s); context anchor Rv3000
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003188|Rv2999|lppY
MAGAKHAGRIVAITTAAAVILAACSSGSKGGAGSGHAGKARSAVTTTDADWKPVADALGRSGKLGDNNTAYRINLPRNDLHITSYGVDIKPGLSLGGYAAFARYDNNETLLMGDLVITEEELPKVTDALQAHGIAQTALHKHLLQQDPPVWWTHIHGMGDAARLAQGLKAALDATTIGPPTPPPARQPPVDIDVAGVDQALGRKGTQDGGLLKYSIPRKDTIIEDGHVLPAVSLNLTTVINFQPVGRGRAAINGDFILIAPEVQEVIRAMRAGNITIVELHNHGLTEEPRLFYMHYWAVDDAVTLARALRPAMDATNLQSS