Rv2901c Still unknown · low auto-curated

H37Rv Rv2901c · MTBC0 mtbc0_003083 · 101 aa · 3232632–3232937 (-) · RefSeq NP_217417.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2469 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2469. Function unknown. Foldseek best (non-significant) hit: 4m7d-assembly1_C Crystal structure of Lsm2-8 complex bound to the RNA (prob 0.16, TM 0.31).

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

Curated reference (UniProt)

UniProt P9WL27 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2901c

UniProt still lists this protein as Uncharacterized protein Rv2901c; 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 (DUF2469)
Orthologous group2AFXT
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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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
DUF2469PF10611.15 3.5e-521–100 Protein of unknown function (DUF2469)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 49.1 (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
4m7d-assembly1_C 0.16 0.31 8.5e-01 4m7d-assembly1_C Crystal structure of Lsm2-8 complex bound to the RNA fragment CGUUU
3jcm-assembly1_d 0.15 0.31 1.0e+00 3jcm-assembly1_d Cryo-EM structure of the spliceosomal U4/U6.U5 tri-snRNP
6n7r-assembly1_M 0.14 0.25 5.6e-01 6n7r-assembly1_M Saccharomyces cerevisiae spliceosomal E complex (ACT1)
3bw1-assembly1_A 0.13 0.29 6.7e-01 3bw1-assembly1_A Crystal structure of homomeric yeast Lsm3 exhibiting novel octameric ring organisation
6j6g-assembly1_g 0.11 0.26 1.1e+00 6j6g-assembly1_g Cryo-EM structure of the yeast B*-a2 complex at an average resolution of 3.2 angstrom
8tew-assembly1_T 0.07 0.42 6.0e+00 8tew-assembly1_T Human cytomegalovirus penton vertex, CVSC-bound configuration
8fnl-assembly1_G 0.07 0.24 1.4e+00 8fnl-assembly1_G Structure of E138K/Q148K HIV-1 intasome with Dolutegravir bound
6g90-assembly1_u 0.05 0.23 3.1e+00 6g90-assembly1_u Prespliceosome structure provides insight into spliceosome assembly and regulation (map A2)

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

Closest characterised functional partner: rnhB (ribonuclease HII), high confidence from genomic context alone (score 821 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2902c rnhB ribonuclease HII 821 821 ctx neighborhood:809
Rv2903c lepB signal peptidase 812 812 ctx neighborhood:802
Rv3219 whiB1 transcriptional regulator WhiB1 773 773 ctx cooccurence:770
Rv3260c whiB2 transcriptional regulator WhiB2 769 770 ctx cooccurence:767
Rv2904c rplS 50S ribosomal protein L19 751 752 ctx neighborhood:748
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 735 736 ctx cooccurence:732
Rv1440 secG protein-export membrane protein SecG 732 733 ctx cooccurence:729
Rv1830 HTH-type transcriptional regulator 732 733 ctx cooccurence:730
Rv3681c whiB4 transcriptional regulator WhiB4 710 711 ctx cooccurence:709
Rv2900c fdhF formate dehydrogenase subunit alpha FdhF 674 675 ctx neighborhood:670
Rv2899c fdhD formate dehydrogenase accessory protein FdhD 673 674 ctx neighborhood:670
Rv3416 whiB3 redox-responsive transcriptional regulator WhiB3 670 671 ctx cooccurence:669
Rv2050 rbpA RNA polymerase-binding protein RbpA 658 658 ctx cooccurence:656
Rv2413c hyp hypothetical protein 658 658 ctx cooccurence:658
Rv2708c hyp hypothetical protein 635 635 ctx cooccurence:630

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: DUF2469 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2469 PF10611.15 (E=4e-52)
  • Foldseek best: 4m7d-assembly1_C Crystal structure of Lsm2-8 complex bound to the RNA fragment C (prob 0.16, E=8e-01, TM=0.31)
  • (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_217417.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2469 (PF10611.15)
  • 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 2AFXT
  • Curated reference: UniProt P9WL27 (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 49.1, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 39 functional partner(s); context anchor rnhB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003083|Rv2901c|
MSAEDLEKYETEMELSLYREYKDIVGQFSYVVETERRFYLANSVEMVPRNTDGEVYFELRLADAWVWDMYRPARFVKQVRVVTFKDVNIEEVEKPELRLPE