Rv2751 Resolved · high auto-curated

H37Rv Rv2751 · MTBC0 mtbc0_002928 · 296 aa · 3086053–3086943 (+) · RefSeq NP_217267.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: LCM (PF04072.21).

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

Curated reference (UniProt)

UniProt I6YEA3 TrEMBL · unreviewed · Evidence at protein level
UniProt nameS-adenosyl-L-methionine-dependent methyltransferase
EC (curated) EC 2.1.1.-
Curated functionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity
Orthologous groupCOG3315

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 0.583 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
LCMPF04072.21 9.1e-4311–193 Leucine carboxyl methyltransferase

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

Closest characterised functional partner: Rv2750 (dehydrogenase), high confidence from genomic context alone (score 901 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2750 dehydrogenase 901 901 ctx neighborhood:882
Rv2749 hyp hypothetical protein 884 884 ctx neighborhood:882
Rv1896c S-adenosyl-L-methionine-dependent methyltransferase 770 770 ctx cooccurence:769
Rv3767c S-adenosylmethionine-dependent methyltransferase 769 769 ctx cooccurence:768
Rv0893c S-adenosylmethionine-dependent methyltransferase 764 765 ctx cooccurence:764
Rv0281 S-adenosylmethionine-dependent methyltransferase 764 764 ctx cooccurence:764
Rv0725c hyp hypothetical protein 762 763 ctx cooccurence:762
Rv1888A Rv1888A, len: 57 aa. Conserved hypothetical protein. Possibly continuation of Rv1889c, part of large family of Mycobacterium tuberculosis pr 651 651 ctx cooccurence:649
Rv1889c Rv1889c, (MTCY180.29), len: 118 aa. Conserved hypothetical protein. Part of large family of Mycobacterium tuberculosis proteins with conserv 621 621 ctx cooccurence:619
Rv2748c ftsK DNA translocase FtsK 615 614 ctx neighborhood:609
Rv3413c rsdA anti-sigma-D factor RsdA 544 544 ctx cooccurence:544
Rv2675c hyp hypothetical protein 520 521 ctx cooccurence:510
Rv3071 hyp hypothetical protein 509 510 ctx cooccurence:508
Rv3699 hyp hypothetical protein 503 504 ctx cooccurence:499
Rv1648 transmembrane protein 482 482 ctx cooccurence:480

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: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): LCM PF04072.21 (E=9e-43)
  • (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_217267.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LCM (PF04072.21)
  • 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 COG3315
  • Curated reference: UniProt I6YEA3 (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 Rv2750
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002928|Rv2751|
MARNPAAQTAFGPMVLAAVEQNEPPGRRLVDDDLADLFLPRPLRWLAGATRSAVLRRLLISASEWSGRGLWANLACRKRFIGDKLDEALGDIDAVVILGAGLDTRAYRLTRRVRMPVFEVDLPVNIARKAKTVRRVLGELPLSVRLVALDFEHDDLLTALAEHGYRTEYRVFFVCEGVTQYLTERAVRRTLEGLRAAAPGSRMVFTYVRRDFIDGTNRYGTRTLYHTVRQRRQLWHFGLDPEEVAGFLADYGWRLTEQAGPEELVQRYVEPTGRNLNASQIEWSAYAEKSEPVTPR