Rv2271 Still unknown · low auto-curated

H37Rv Rv2271 · MTBC0 mtbc0_002413 · 99 aa · 2571437–2571736 (+) · RefSeq NP_216787.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2695 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2695. Function unknown. Foldseek best (non-significant) hit: 7kuw-assembly1_A High-throughput design and refinement of stable prote (prob 0.04, TM 0.37).

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

Curated reference (UniProt)

UniProt P9WLF7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2271

UniProt still lists this protein as Uncharacterized protein Rv2271; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2695)
Orthologous group2B2YH

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, 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)

PfamAccessioni-EvalueResiduesDescription
DUF2695PF10905.14 4.7e-2739–91 Protein of unknown function (DUF2695)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 50.2 (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
7kuw-assembly1_A 0.04 0.37 5.2e+00 7kuw-assembly1_A High-throughput design and refinement of stable proteins using sequence-only models
8pv2-assembly1_CQ 0.01 0.24 9.6e+00 8pv2-assembly1_CQ Chaetomium thermophilum pre-60S State 10 - pre-5S rotation with Ytm1-Erb1

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

Closest characterised functional partner: lppN (lipoprotein LppN), medium confidence from genomic context alone (score 577 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2270 lppN lipoprotein LppN 577 577 ctx neighborhood:576
Rv2272 transmembrane protein 546 546 ctx neighborhood:534
Rv2273 transmembrane protein 539 538 ctx neighborhood:534

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: DUF2695 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2695 PF10905.14 (E=5e-27)
  • Foldseek best: 7kuw-assembly1_A High-throughput design and refinement of stable proteins using (prob 0.04, E=5e+00, TM=0.37)
  • (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_216787.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2695 (PF10905.14)
  • 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 2B2YH
  • Curated reference: UniProt P9WLF7 (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 50.2, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s); context anchor lppN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002413|Rv2271|
MTTPPDKARRRFLRDAYKNAERVARTALLTIDQDQLEQLLDYVDERLGEQPCDHTARHAQRWAQSHRIEWETLAEGLQEFGGYCDCEIVMNVEPEAIFG