Rv2411c Resolved · high auto-curated

H37Rv Rv2411c · MTBC0 mtbc0_002567 · 551 aa · 2732578–2734233 (-) · RefSeq NP_216927.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationcircularly permuted type 2 ATP-grasp protein
Revised (this work)Circularly permuted type 2 ATP-grasp protein. Pfam: CP_ATPgrasp_1 (PF04174.19), CP_ATPgrasp_2 (PF14403.12).

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

Curated reference (UniProt)

UniProt P9WLA9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2411c

UniProt still lists this protein as Uncharacterized protein Rv2411c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namegcs2
eggNOG descriptionCircularly permuted ATP-grasp type 2
Orthologous groupCOG2308

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 0.34 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 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
CP_ATPgrasp_1PF04174.19 1.5e-169100–431 A circularly permuted ATPgrasp
CP_ATPgrasp_2PF14403.12 9.6e-163100–476 Circularly permuted ATP-grasp type 2

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

Closest characterised functional partner: Rv0433 (carboxylate-amine ligase), high confidence from genomic context alone (score 876 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2410c hyp hypothetical protein 997 998 ctx neighborhood:882 cooccurence:774 coexpression:885
Rv2409c hyp hypothetical protein 993 993 ctx neighborhood:882 cooccurence:774 coexpression:754
Rv0433 carboxylate-amine ligase 876 876 ctx fusion:868
Rv2566 hyp hypothetical protein 852 847 ctx neighborhood:526 cooccurence:660
Rv2569c hyp hypothetical protein 807 801 ctx cooccurence:774
Rv2412 rpsT 30S ribosomal protein S20 632 632 ctx neighborhood:630
Rv2567 hyp hypothetical protein 520 498
Rv2568c hyp hypothetical protein 430 430

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: circularly permuted type 2 ATP-grasp protein
  • Pfam (hmmscan --cut_ga): CP_ATPgrasp_1 PF04174.19 (E=1e-169), CP_ATPgrasp_2 PF14403.12 (E=1e-162)
  • (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_216927.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CP_ATPgrasp_1 (PF04174.19), CP_ATPgrasp_2 (PF14403.12)
  • 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 COG2308
  • Curated reference: UniProt P9WLA9 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 8 functional partner(s); context anchor Rv0433
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002567|Rv2411c|
MRRVSLPNQLNETRRRSPTRGERIFGGYNTSDVYAMAFDEMFDAQGIVRGPYKGIYAELAPSDASELKARADALGRAFIDQGITFSLSGQERPFPLDLVPRVISAPEWTRLERGITQRVKALECYLDDIYGDQEILRDGVIPRRLVTSCEHFHRQAVGIVPPNGVRIHVAGIDLIRDHRGDFRVLEDNLRSPSGVSYVMENRRTMARVFPNLFATHRVRAVDDYASHLLRALRNSAATNEADPTVVVLTPGVYNSAYFEHSLLARQMGVELVEGRDLFCRDNQVYMRTTEGERQVDVIYRRIDDAFLDPLQFRADSVLGVAGLVNAARAGNVVLSSAIGNGVGDDKLVYTYVPTMIEYYLHEKPLLANVETLRCWLDDEREEVLDRIRELVLKPVEGSGGYGIVFGPEASQAELAAVSQKIRDDPRSWIAQPMMELSTVPTRIEGTLAPRYVDLRPFAVNDGNEVWVLPGGLTRVALVEGSRVVNSSQGGGSKDTWVLAPRASAAARELGAAQIVRSLPQPLCDPTVDASGYEPHDQQPQQQQQQQQQAFH