Rv1914c Still unknown · low auto-curated

H37Rv Rv1914c · MTBC0 mtbc0_002029 · 135 aa · 2178031–2178438 (-) · RefSeq NP_216430.1

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: 2ys5-assembly1_A Solution structure of the complex of the PTB domain o (prob 0.38, TM 0.51).

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

Curated reference (UniProt)

UniProt O07719 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 group2CK29

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, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.18% of strains (256) · 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 71.8 (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
2ys5-assembly1_A 0.38 0.51 5.5e-01 2ys5-assembly1_A Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of hALK
8emv-assembly1_A 0.38 0.40 1.4e-01 8emv-assembly1_A Phospholipase C beta 3 (PLCb3) in solution
4qj3-assembly1_B 0.33 0.44 3.6e-01 4qj3-assembly1_B Structure of a fragment of human phospholipase C-beta3 delta472-559, in complex with Galphaq
4qj5-assembly1_B 0.30 0.43 3.0e-01 4qj5-assembly1_B Structure of a fragment of human phospholipase C-beta3 delta472-581, bound to IP3 and in complex with Galphaq
8uqo-assembly1_Q 0.25 0.41 4.1e-01 8uqo-assembly1_Q PLCb3-Gbg-Gaq complex on membranes
4qj4-assembly1_B 0.23 0.43 4.9e-01 4qj4-assembly1_B Structure of a fragment of human phospholipase C-beta3 delta472-569, bound to IP3 and in complex with Galphaq
2p1r-assembly2_D 0.21 0.50 5.2e-01 2p1r-assembly2_D Crystal structure of Salmonella typhimurium YegS, a putative lipid kinase homologous to eukaryotic sphingosine and diacylglycerol kinases.
4gnk-assembly2_D 0.20 0.39 3.6e-01 4gnk-assembly2_D Crystal structure of Galphaq in complex with full-length human PLCbeta3

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

Closest characterised functional partner: aceAb (isocitrate lyase AceAb), medium confidence from genomic context alone (score 554 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1916 aceAb isocitrate lyase AceAb 554 554 ctx neighborhood:552
Rv1915 aceAa isocitrate lyase AceAa 552 552 ctx neighborhood:552

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: 2ys5-assembly1_A Solution structure of the complex of the PTB domain of SNT-2 an (prob 0.38, E=5e-01, TM=0.51)
  • (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_216430.1)
  • 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 2CK29
  • Curated reference: UniProt O07719 (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 71.8, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 2 functional partner(s); context anchor aceAb
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002029|Rv1914c|
MVLSRTSTGRVILVPTQLRFDRWFLPLAVPLGLGPKNSELWVGAGSLHVKMGWAFAADIPLTSITKAEATNARVYAAGVHFGFGRWLVNGSRKGLVALTIDPPEQAKMWKKSMTVRELWVSVTDPDALVTACTAK