Rv2141c Family assigned · medium auto-curated

H37Rv Rv2141c · MTBC0 - · 448 aa · 2400376–2401722 (-) · RefSeq YP_177864.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Peptidase_M28 (PF04389.23), Peptidase_M20 (PF01546.34), M20_dimer (PF07687.20) domain(s); putative function inferred from the domain architecture.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt L7N684 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namedapE2
eggNOG descriptiondeacetylase Succinyl-diaminopimelate desuccinylase and related deacylases
Orthologous groupCOG0624

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 1.179 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 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
Peptidase_M28PF04389.23 8.9e-1069–169 Peptidase family M28
Peptidase_M20PF01546.34 5.2e-3185–446 Peptidase family M20/M25/M40
M20_dimerPF07687.20 3.3e-14206–332 Peptidase dimerisation domain

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

Closest characterised functional partner: ctaF (cytochrome c oxidase polypeptide 4), medium confidence from genomic context alone (score 492 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2140c TB18.6 hyp hypothetical protein 832 827 ctx neighborhood:816
Rv1652 argC N-acetyl-gamma-glutamyl-phoshate reductase 545 497 coexpression:403
Rv2199c ctaF cytochrome c oxidase polypeptide 4 492 492 ctx cooccurence:473
Rv1658 argG argininosuccinate synthase 520 468
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 497 443 experimental:419
Rv2146c transmembrane protein 439 440
Rv2096c pafB proteasome accessory factor B 430 430 ctx cooccurence:430
Rv2467 pepN aminopeptidase PepN 414 352
Rv1202 dapE succinyl-diaminopimelate desuccinylase DapE 504 199 textmining:407

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): Peptidase_M28 PF04389.23 (E=9e-10), Peptidase_M20 PF01546.34 (E=5e-31), M20_dimer PF07687.20 (E=3e-14)
  • (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 YP_177864.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M28 (PF04389.23), Peptidase_M20 (PF01546.34), M20_dimer (PF07687.20)
  • 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 COG0624
  • Curated reference: UniProt L7N684 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 9 functional partner(s); context anchor ctaF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2141c|
MTDETGASSDHSDDVAQVVSRLIRFDTTNSGEPGTTKGEAECARWVAEQLAEVGYQPEYVESGAPGRGNVFARLAGADSSRGALLIHGHLDVVPAEPAEWSVHPFSGAIEDGYVWGRGAVDMKDMVGMMIVVARHLRQAAIVPPRDLVFAFVADEEHGGKYGSHWLVDNRPDLFDGITEAIGEVGGFSLTVPRHDGGERRLYLIETAEKGIQWMRLTARGRAGHGSMVHDQNAVTAVCEAVARLGRHQFPLVCTDTVAQFLAVVGEETGLAFDLDSPDLAGTIDKLGPMARMLKAVLHDTANPTMLKAGYKANVVPATAEAVVDCRVLPGRRAAFEAEVDALIGPDVTREWVSDLPSYETTFDGDLVAAMNAAVLAVDPDGRTVPYMLSGGTDAKAFARLGIRCFGFSPLRLPPDLDFTSLFHGVDERVPIDGLRFGTEVLTHLLTHC