Rv2084 Still unknown · low auto-curated

H37Rv Rv2084 · MTBC0 mtbc0_002220 · 331 aa · 2370421–2371568 (+) · RefSeq NP_216600.1

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: 1l7c-assembly1_A alpha-catenin fragment, residues 385-651 (prob 0.21, TM 0.26).

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

Curated reference (UniProt)

UniProt P9WLK1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2084

UniProt still lists this protein as Uncharacterized protein Rv2084; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2B714
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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 0.466 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 0 nonsense, 4 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 60.94% of strains (88485) · reference-fixed

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 60.3 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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
1l7c-assembly1_A 0.21 0.26 7.3e-01 1l7c-assembly1_A alpha-catenin fragment, residues 385-651
3o43-assembly1_A 0.18 0.35 1.5e+00 3o43-assembly1_A Complex of an alpha/beta-peptide based on the gp41 CHR domain bound to gp41-5
5xfl-assembly2_B 0.18 0.29 1.6e+00 5xfl-assembly2_B Crystal structure of the force-sensing device region of alpha N-catenin
5v54-assembly1_B 0.18 0.23 4.0e-01 5v54-assembly1_B Crystal structure of 5-HT1B receptor in complex with methiothepin
4dzv-assembly1_A 0.16 0.31 1.3e+00 4dzv-assembly1_A Complex of 4-alpha/beta bound to gp41-5
4p9t-assembly1_C 0.15 0.36 3.9e+00 4p9t-assembly1_C Structure of the free form of the N-terminal VH1 domain of monomeric alpha-catenin
4dzu-assembly1_A 0.13 0.34 2.9e+00 4dzu-assembly1_A Complex of 3-alpha bound to gp41-5
6rz5-assembly2_B 0.12 0.19 5.1e-01 6rz5-assembly2_B XFEL crystal structure of the human cysteinyl leukotriene receptor 1 in complex with zafirlukast

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

Closest characterised functional partner: Rv2081c (transmembrane protein), medium confidence from genomic context alone (score 494 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2083 hyp hypothetical protein 853 853 ctx neighborhood:801
Rv2082 hyp hypothetical protein 807 807 ctx neighborhood:801
Rv2085 hyp hypothetical protein 572 572 ctx neighborhood:552
Rv2086 hyp hypothetical protein 562 563 ctx neighborhood:552
Rv2081c transmembrane protein 494 494 ctx neighborhood:491
Rv2087 Rv2087, (MTCY49.27), len: 76 aa. Conserved hypothetical protein, similar to but shorter than transposases, but we can find no sequence error 413 412 ctx neighborhood:410

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: 1l7c-assembly1_A alpha-catenin fragment, residues 385-651 (prob 0.21, E=7e-01, TM=0.26)
  • (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_216600.1)
  • 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 2B714
  • Curated reference: UniProt P9WLK1 (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 60.3, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 6 functional partner(s); context anchor Rv2081c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002220|Rv2084|
MSDDSSSAFDLICAEIERQLRGGELLMDAAAASELLLTVRYQLDTQPRPLVIVHGPLFQAVKAARAQVYGRLIQLRHARCEVLDERWQLRPTGQRDVRALLIDVLNVLLAAITAAGVERAYACAERRAMAAAVVAKNYRDALGVELQCNSVCRAAAEAIHALAHRTGATEDADCLPPVDVIHADVTRRMHGEVATDVVAAGELVIAARHLLDPMPRGELSYGPLHEGGNAARKSVYRRLVQLWQARRAVTDGDVDLRDARTLLTDLDSILREMRTAATIQQAYTRAERRAMAAAVVAKIRGDAMGLDAQRDAVHRAAADALHALQSVGIHQ