Rv2114 Still unknown · low auto-curated

H37Rv Rv2114 · MTBC0 mtbc0_002246 · 207 aa · 2401097–2401720 (+) · RefSeq NP_216630.1

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: 8b6h-assembly1_ES Cryo-EM structure of cytochrome c oxidase dimer (com (prob 0.08, TM 0.34).

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

Curated reference (UniProt)

UniProt O33249 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2D663

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 0.331 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.53% of strains (767) · 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)

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 38.9 (very 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
8b6h-assembly1_ES 0.08 0.34 3.6e+00 8b6h-assembly1_ES Cryo-EM structure of cytochrome c oxidase dimer (complex IV) from respiratory supercomplex of Tetrahymena thermophila
8gzu-assembly1_0G 0.08 0.35 3.6e+00 8gzu-assembly1_0G Cryo-EM structure of Tetrahymena thermophila respiratory Megacomplex MC (IV2+I+III2+II)2
8dgf-assembly1_C 0.02 0.21 7.2e+00 8dgf-assembly1_C Avs4 bound to phage PhiV-1 portal
4yj2-assembly1_E 0.01 0.18 8.1e+00 4yj2-assembly1_E Crystal structure of tubulin bound to MI-181
7xqx-assembly1_E 0.01 0.18 7.6e+00 7xqx-assembly1_E Crystal structure of T2R-TTL-27a complex
6o5n-assembly1_E 0.01 0.18 9.1e+00 6o5n-assembly1_E Tubulin-RB3_SLD-TTL in complex with compound 10ab
4yj3-assembly1_E 0.01 0.18 9.1e+00 4yj3-assembly1_E Crystal structure of tubulin bound to compound 2
7dbd-assembly1_E 0.01 0.18 9.1e+00 7dbd-assembly1_E 444 in complex with tubulin

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

Closest characterised functional partner: Rv2113 (integral membrane protein), high confidence from genomic context alone (score 924 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2113 integral membrane protein 924 924 ctx neighborhood:874 cooccurence:418
Rv1006 hyp hypothetical protein 761 761 ctx cooccurence:759
Rv1868 hyp hypothetical protein 745 745 ctx cooccurence:745
Rv1435c hyp hypothetical protein 735 736 ctx cooccurence:735
Rv2047c hyp hypothetical protein 635 635 ctx cooccurence:635
Rv3033 hyp hypothetical protein 626 626 ctx cooccurence:624
Rv0180c transmembrane protein 611 611 ctx cooccurence:610
Rv2112c dop pup deamidase/depupylase 606 605 ctx neighborhood:604
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 559 559 ctx cooccurence:557
Rv1748 hyp hypothetical protein 552 552 ctx cooccurence:552
Rv1364c sigma factor regulatory protein 546 546 ctx cooccurence:546
Rv2598 hyp hypothetical protein 501 502 ctx cooccurence:500
Rv3887c eccD2 ESX-2 secretion system protein EccD 489 489 ctx cooccurence:489
Rv3899c hyp hypothetical protein 475 476 ctx cooccurence:474
Rv0258c hyp hypothetical protein 451 451 ctx cooccurence:451

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: 8b6h-assembly1_ES Cryo-EM structure of cytochrome c oxidase dimer (complex IV) f (prob 0.08, E=4e+00, TM=0.34)
  • (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_216630.1)
  • 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 2D663
  • Curated reference: UniProt O33249 (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 38.9, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 21 functional partner(s); context anchor Rv2113
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002246|Rv2114|
MSAPERVTGLSGQRYGEVLLVTPGEAGPQATVYNSFPLNDCPAELWSALDPQALATEHKAATALLNGPRYWLMNAIEKAPQGPPVTKTFGGIEMLQQATVLLSSMNPAPYTVSQVSRNTVFVFNAGEEVYELQDPKGQRWVMQTWSQVVDPNLSRADLPKLGERLNLPAGWSYHTRVLTSELRVDTTNREARVLQDDLTNSYSLVTA