Rv2125 Family assigned · medium auto-curated

H37Rv Rv2125 · MTBC0 mtbc0_002257 · 292 aa · 2413556–2414434 (+) · RefSeq NP_216641.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationPAC2 family protein
Revised (this work)PAC2 family protein. Pfam: PAC2 (PF09754.16).

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

Curated reference (UniProt)

UniProt O33260 TrEMBL · unreviewed · Evidence at protein level
UniProt namePAC2 family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPAC2 family
Orthologous groupCOG2047

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 0.067 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 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
PAC2PF09754.16 2.2e-6321–238 PAC2 family

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

Closest characterised functional partner: metH (methionine synthase), high confidence from genomic context alone (score 753 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2124c metH methionine synthase 882 753 ctx neighborhood:750 textmining:543
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 633 634 ctx cooccurence:627
Rv1456c antibiotic ABC transporter permease 554 554 ctx cooccurence:554
Rv0121c hyp hypothetical protein 511 511 coexpression:447
Rv1828 HTH-type transcriptional regulator 501 501 ctx cooccurence:498
Rv1321 nucS endonuclease NucS 480 481 ctx cooccurence:473
Rv0504c hyp hypothetical protein 479 480 ctx cooccurence:477
Rv2110c prcB proteasome subunit beta 496 466
Rv3129 Rv3129, (MTCY164.40), len: 110 aa. Conserved hypothetical protein, with some similarity to various hypothetical proteins from Streptomyces c 450 450 coexpression:450
Rv0080 hyp hypothetical protein 449 450 coexpression:450
Rv2109c prcA proteasome subunit alpha 479 449
Rv1875 hyp hypothetical protein 449 449 coexpression:449
Rv0884c serC phosphoserine aminotransferase 447 447 ctx cooccurence:439
Rv2242 hyp hypothetical protein 439 440 ctx cooccurence:436
Rv1457c antibiotic ABC transporter permease 438 439 ctx cooccurence:435

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: PAC2 family protein
  • Pfam (hmmscan --cut_ga): PAC2 PF09754.16 (E=2e-63)
  • (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_216641.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PAC2 (PF09754.16)
  • 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 COG2047
  • Curated reference: UniProt O33260 (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 — 26 functional partner(s); context anchor metH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002257|Rv2125|
MTPSEGNAPLPELHNTVVVAAFEGWNDAGDAASDAVAHLAASWQALPIVEIDDEAYYDYQVNRPVIRQVDGVTRELQWPAMRISHCRPPGSDRDVVLMCGVEPNMRWRTFCDELLAVIDKLNVDTVVILGALLADTPHTRPVPVSGAAYSAASARQFGLQETRYEGPTGIAGVFQSACVGAGIPAVTFWAAVPHYVSHPPNPKATIALLRRVEDVLDVEVPLADLPAQAEAWEREITETIAEDHELAEYVQTLEQHGDAAVDMNEALGNIDGDALAAEFERYLRRRRPGFGR