Rv0559c Family assigned · low

H37Rv Rv0559c · MTBC0 mtbc0_000588 · 112 aa · 653958–654296 (-) · RefSeq NP_215073.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF732 domain-containing protein
Revised (this work)Lipoprotein of the LprJ-like family (secreted, salicylate/rifampicin-stress-induced). RefSeq leaves it 'hypothetical protein'.

Curated reference (UniProt)

UniProt P9WKL3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0559c

UniProt still lists this protein as Uncharacterized protein Rv0559c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF732)
Orthologous group2A2PD
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944

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 0.321 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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)

PfamAccessioni-EvalueResiduesDescription
DUF732PF05305.20 8.4e-1129–101 Protein of unknown function (DUF732)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 77.0 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
6zol-assembly1_R 0.04 0.37 9.5e+00 6zol-assembly1_R SARS-CoV-2-Nsp1-40S complex, focused on head
7odt-assembly1_c 0.01 0.20 9.5e+00 7odt-assembly1_c State C of the human mitoribosomal large subunit assembly intermediate

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

Closest characterised functional partner: menJ (oxidoreductase), medium confidence from genomic context alone (score 684 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0561c menJ oxidoreductase 849 684 ctx neighborhood:684 textmining:543
Rv0560c benzoquinone methyltransferase 951 668 ctx neighborhood:668 textmining:860
Rv0562 grcC1 polyprenyl-diphosphate synthase GrcC 520 520 ctx neighborhood:520
Rv0455c hyp hypothetical protein 665 73 textmining:654
Rv2536 transmembrane protein 805 41 textmining:805
Rv0379 secE2 protein translocase subunit SecE 751 41 textmining:751
Rv2284 lipM esterase LipM 657 41 textmining:657
Rv1508c membrane protein 651 41 textmining:651
Rv0261c narK3 nitrate/nitrite transporter 548 41 textmining:548
Rv3707c hyp hypothetical protein 433 41 textmining:433

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

  • Foldseek vs AFDB-SwissProt: lipoprotein LprJ, TM 0.59, E 3e-3
  • Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.

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_215073.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF732 (PF05305.20)
  • 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 2A2PD
  • Curated reference: UniProt P9WKL3 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 77.0, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 10 functional partner(s); context anchor menJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000588|Rv0559c|
MKGTKLAVVVGMTVAAVSLAAPAQADDYDAPFNNTIHRFGIYGPQDYNAWLAKISCERLSRGVDGDAYKSATFLQRNLPRGTTQGQAFQFLGAAIDHYCPEHVGVLQRAGTR