Rv1476 Family assigned · medium auto-curated

H37Rv Rv1476 · MTBC0 mtbc0_001579 · 186 aa · 1676009–1676569 (+) · RefSeq NP_215992.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationDUF6676 family protein
Revised (this work)DUF6676 family protein. Pfam: Rv1476 (PF20381.5).

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

Curated reference (UniProt)

UniProt O53167 SwissProt · reviewed · Evidence at protein level
UniProt nameMembrane protein Rv1476
Curated functionMay affect the expression of genes linked to host macrophage apoptosis and immune response, thereby promoting the survival of M.tuberculosis in host macrophages. Overexpression of the gene increases susceptibility of the bacteria to various stresses, but promotes intracellular survival in host macrophages. It has no impact on the growth rate in vitro. Overexpression causes changes in the transcriptome of THP-1 cells, including expression of genes involved in cell proliferation, fatty acid degradation, cytokine-cytokine receptor interaction and immune response pathways.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2C0SM

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 0 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
Rv1476PF20381.5 6.6e-6216–171 Membrane protein Rv1476

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

Closest characterised functional partner: aftC (alpha-(1->3)-arabinofuranosyltransferase), high confidence from genomic context alone (score 776 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 776 776 ctx cooccurence:773
Rv3802c membrane protein 774 774 ctx cooccurence:773
Rv3035 hyp hypothetical protein 772 772 ctx cooccurence:771
Rv1274 lprB lipoprotein LprB 768 768 ctx cooccurence:767
Rv0479c membrane protein 767 767 ctx cooccurence:764
Rv3794 embA arabinosyltransferase A 766 767 ctx cooccurence:764
Rv0227c membrane protein 766 766 ctx cooccurence:759
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 765 765 ctx cooccurence:764
Rv1275 lprC lipoprotein LprC 760 760 ctx cooccurence:757
Rv3668c protease 759 759 ctx cooccurence:759
Rv3244c lpqB lipoprotein LpqB 757 758 ctx cooccurence:756
Rv3346c transmembrane protein 756 756 ctx cooccurence:755
Rv2342 hyp hypothetical protein 752 752 ctx cooccurence:750
Rv3795 embB arabinosyltransferase B 751 752 ctx cooccurence:750
Rv0226c transmembrane protein 745 746 ctx cooccurence:744

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: membrane protein
  • MTBC0 PGAP product: DUF6676 family protein
  • Pfam (hmmscan --cut_ga): Rv1476 PF20381.5 (E=7e-62)
  • (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_215992.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv1476 (PF20381.5)
  • 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 2C0SM
  • Curated reference: UniProt O53167 (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 — 100 functional partner(s); context anchor aftC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001579|Rv1476|
MTGPYFPQTIPFLPSYIPQDVDMTAVKAEVAALGVSAPPAATPGLLEVVQHARDEGIDLKIVLLDHNPPNDTPLRDIATVVGADYSDATVLVLSPNYVGSYSTQYPRVTLEAGEDHSKTGNPVQSAQNFVHELSTPEFPWSALTIVLLIGVLAAAVGARLMQLRGRRSATSTDAAPGAGDDLNQGV