Rv1778c Still unknown · low

H37Rv Rv1778c · MTBC0 mtbc0_001892 · 149 aa · 2030092–2030541 (-) · RefSeq NP_216294.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical; Foldseek best hit (RbmA, TM 0.38) not conclusive. Function unknown.

Curated reference (UniProt)

UniProt O33181 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2E3FZ

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (337) · 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
DUF6941PF22091.3 7.8e-115–130 Family of unknown function (DUF6941)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 84.5 (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
4be6-assembly1_A 1.00 0.38 1.0e-03 sig 4be6-assembly1_A V. cholera biofilm scaffolding protein RbmA
6ru5-assembly1_A 1.00 0.49 1.5e-02 6ru5-assembly1_A human complement C3 in complex with the hC3Nb1 nanobody
8cem-assembly1_E 1.00 0.45 8.6e-03 sig 8cem-assembly1_E Structure of bovine native C3, re-refinement
2wii-assembly1_A 1.00 0.45 5.6e-03 sig 2wii-assembly1_A Complement C3b in complex with factor H domains 1-4
8enu-assembly1_G 0.99 0.56 4.7e-02 8enu-assembly1_G Structure of the C3bB proconvertase in complex with lufaxin
4bei-assembly1_H 0.99 0.40 3.5e-03 sig 4bei-assembly1_H V. cholera biofilm scaffolding protein RbmA in complex with 18-crown- 6
6yo6-assembly1_A 0.99 0.43 1.1e-02 6yo6-assembly1_A Structure of iC3b1
8ovb-assembly1_A 0.99 0.48 2.6e-02 8ovb-assembly1_A Human Complement C3b in complex with Trypanosoma brucei ISG65.

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

Closest characterised functional partner: Rv1779c (integral membrane protein), medium confidence from genomic context alone (score 540 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1779c integral membrane protein 540 540 ctx neighborhood:540

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

  • MTBC0 PGAP product: hypothetical protein
  • Pfam: DUF6941 PF22091.3
  • Foldseek best: 4be6-assembly1_A V. cholera biofilm scaffolding protein RbmA (prob 1.00, E=1e-03, TM=0.38)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_216294.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6941 (PF22091.3)
  • 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 2E3FZ
  • Curated reference: UniProt O33181 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 84.5, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 1 functional partner(s); context anchor Rv1779c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001892|Rv1778c|
MRVSLFLSDAAQADAQSGKVHALGLGWRQCQTPTPPFALVLFLDIDWDETNKQHQLKCQLLTADGDPVVVPGPHGPQRILFEAAAEAGRAPGAIHGTSVRMPLTLNIPAGIPLEPGIYEWRVEVEGYERATAVEAFIVAGGGHPPASCG