Rv2257c Family assigned · medium auto-curated

H37Rv Rv2257c · MTBC0 mtbc0_002400 · 272 aa · 2556164–2556982 (-) · RefSeq NP_216773.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationserine hydrolase domain-containing protein
Revised (this work)Serine hydrolase domain-containing protein. Pfam: Beta-lactamase (PF00144.30).

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

Curated reference (UniProt)

UniProt O53531 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 V Defense mechanisms
Preferred namebla
eggNOG descriptionbeta-lactamase
Orthologous groupCOG1680

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 0.742 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
Beta-lactamasePF00144.30 1.7e-3313–254 Beta-lactamase

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

Closest characterised functional partner: Rv2258c (transcriptional regulator), high confidence from genomic context alone (score 879 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2258c transcriptional regulator 878 879 ctx neighborhood:872
Rv1614 lgt prolipoprotein diacylglyceryl transferase 793 794 coexpression:788
Rv2256c hyp hypothetical protein 759 760 ctx neighborhood:759
Rv2259 mscR S-nitrosomycothiol reductase MscR 702 703 ctx neighborhood:689
Rv2260 hyp hypothetical protein 704 695 ctx neighborhood:689
Rv0194 multidrug ABC transporter ATPase/permease 423 402
Rv2610c pimA alpha-(1-2)-phosphatidylinositol mannosyltransferase 421 302
Rv1209 hyp hypothetical protein 555 241 textmining:438
Rv2613c AP-4-A phosphorylase 812 86 textmining:803
Rv1301 threonylcarbamoyl-AMP synthase 459 85 textmining:434
Rv2681 hyp hypothetical protein 442 55 textmining:434

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: serine hydrolase domain-containing protein
  • Pfam (hmmscan --cut_ga): Beta-lactamase PF00144.30 (E=2e-33)
  • (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_216773.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Beta-lactamase (PF00144.30)
  • 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 COG1680
  • Curated reference: UniProt O53531 (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 — 11 functional partner(s); context anchor Rv2258c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002400|Rv2257c|
MTALEVLGGWPVPAAAAAVIGPAGVLATHGDTARVFALASVTKPLVARAAQVAVEEGVVNLDTPAGPPGSTVRHLLAHTSGLAMHSDQALARPGTRRMYSNYGFTVLAESVQRESGIEFGRYLTEAVCEPLGMVTTRLDGGPAAAGFGATSTVADLAVFAGDLLRPSTVSAQMHADATTVQFPGLDGVLPGYGVQRPNDWGLGFEIRNSKSPHWTGECNSTRTFGHFGQSGGFIWVDPKADLALVVLTARDFGDWALDLWPAISDAVLAEYT