Rv1951c Still unknown · low auto-curated

H37Rv Rv1951c · MTBC0 mtbc0_002066 · 98 aa · 2219306–2219602 (-) · RefSeq NP_216467.1

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: 6z6f-assembly1_C HDAC-PC (prob 0.15, TM 0.64).

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

Curated reference (UniProt)

UniProt P95263 TrEMBL · unreviewed · Predicted
UniProt namePE family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2B0F7

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 0.733 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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 61.7 (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
6z6f-assembly1_C 0.15 0.64 8.4e+00 6z6f-assembly1_C HDAC-PC
4lws-assembly3_A 0.12 0.47 3.8e+00 4lws-assembly3_A EsxA : EsxB (SeMet) hetero-dimer from Thermomonospora curvata
6z6o-assembly1_C 0.08 0.47 6.8e+00 6z6o-assembly1_C HDAC-TC

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

Closest characterised functional partner: Rv1949c (Rv1949c, (MTCY09F9.15), len: 319 aa. Conserved hypothetical protein, partial ORF. Rv1949c and Rv1950c|MTCY09F9.14 are similar but frameshift), high confidence from genomic context alone (score 833 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1950c hyp hypothetical protein 884 884 ctx neighborhood:882
Rv1949c Rv1949c, (MTCY09F9.15), len: 319 aa. Conserved hypothetical protein, partial ORF. Rv1949c and Rv1950c|MTCY09F9.14 are similar but frameshift 833 833 ctx neighborhood:828
Rv1948c hyp hypothetical protein 814 815 ctx neighborhood:814
Rv1952 vapB14 antitoxin VapB14 466 466 ctx neighborhood:463
Rv1953 vapC14 ribonuclease VapC14 465 465 ctx neighborhood:463

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: 6z6f-assembly1_C HDAC-PC (prob 0.15, E=8e+00, TM=0.64)
  • (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_216467.1)
  • 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 2B0F7
  • Curated reference: UniProt P95263 (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 61.7, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 5 functional partner(s); context anchor Rv1949c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002066|Rv1951c|
MKAGELRVNIQQVAATASQWSGRSTELSVLAPPPLGQPFQPTTAAVGGAHAAVGLAVAAFTARTHATASAVEAAAAEYANNEAAAAAEMAAVPQTRLV