Rv2808 Still unknown · low auto-curated

H37Rv Rv2808 · MTBC0 mtbc0_002988 · 85 aa · 3137461–3137718 (+) · RefSeq NP_217324.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 6fnd-assembly1_B Crystal structure of Toxoplasma gondii AKMT (prob 0.16, TM 0.54).

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

Curated reference (UniProt)

UniProt P71643 TrEMBL · unreviewed · Predicted
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 group291GV

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) 2 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 90.8 (very high). 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
6fnd-assembly1_B 0.16 0.54 4.4e+00 6fnd-assembly1_B Crystal structure of Toxoplasma gondii AKMT
5mq1-assembly1_A 0.10 0.43 4.0e+00 5mq1-assembly1_A Crystal structure of the BRD7 bromodomain in complex with BI-9564
4hwd-assembly3_B 0.09 0.39 4.4e+00 4hwd-assembly3_B Crystal structure of ATBAG2
8y3y-assembly1_D 0.09 0.45 4.7e+00 8y3y-assembly1_D The Cryo-EM structure of anti-phage defense associated DSR2 tetramer bound with two DSAD1 inhibitors (opposite side)
1xg2-assembly1_B 0.08 0.41 6.2e+00 1xg2-assembly1_B Crystal structure of the complex between pectin methylesterase and its inhibitor protein
3kav-assembly1_A 0.07 0.39 6.6e+00 3kav-assembly1_A Crystal Structure of THE MUTANT (L80M) PA2107 PROTEIN from Pseudomonas aeruginosa, Northeast Structural Genomics Consortium Target PaR198
8y3m-assembly1_B 0.07 0.51 9.2e+00 8y3m-assembly1_B Cryo-EM structure of DSR2-DSAD1 complex (cross-linked)
8zak-assembly1_A 0.06 0.30 3.5e+00 8zak-assembly1_A Crystal structure of the channel protein CorA from Campylobacter jejuni in complex with Ni2+

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2809 hyp hypothetical protein 576 576 ctx neighborhood:561
Rv2807 hyp hypothetical protein 428 428 ctx neighborhood:428
Rv3766 hyp hypothetical protein 660 47 textmining:658
Rv2004c hyp hypothetical protein 441 47 textmining:438
Rv2003c hyp hypothetical protein 545 46 textmining:543
Rv3459c rpsK 30S ribosomal protein S11 433 46 textmining:431
Rv2283 hyp hypothetical protein 804 41 textmining:804
Rv2402 trehalase 547 41 textmining:547
Rv3128c Rv3128c, (MTCY164.38c), len: 337 aa. Conserved hypothetical protein, similar to other conserved hypothetical proteins. This ORF corresponds 426 41 textmining:427

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: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 6fnd-assembly1_B Crystal structure of Toxoplasma gondii AKMT (prob 0.16, E=4e+00, TM=0.54)
  • (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_217324.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 291GV
  • Curated reference: UniProt P71643 (TrEMBL, unreviewed; Predicted)
  • 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 90.8, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 9 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002988|Rv2808|
MSNVLDAISTEHRPVIEQELENRNPALFDELRRTEKPTNEQSDAVIDVLSDALMKTFGPDWVPNDYGLKIERAIDAYLETWPIYR