Rv2148c Family assigned · medium auto-curated

H37Rv Rv2148c · MTBC0 mtbc0_002284 · 258 aa · 2434219–2434995 (-) · RefSeq NP_216664.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationYggS family pyridoxal phosphate-dependent enzyme
Revised (this work)YggS family pyridoxal phosphate-dependent enzyme. Pfam: Ala_racemase_N (PF01168.27).

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

Curated reference (UniProt)

UniProt P9WFQ7 SwissProt · reviewed · Evidence at protein level
UniProt namePyridoxal phosphate homeostasis protein
Curated functionPyridoxal 5'-phosphate (PLP)-binding protein, which is involved in PLP homeostasis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPyridoxal 5'-phosphate (PLP)-binding protein, which is involved in PLP homeostasis
Orthologous groupCOG0325
KEGG orthology K06997
Gene Ontology (17) GO:0003674, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0008144, GO:0019842, GO:0030170, GO:0036094, GO:0043167, GO:0043168, GO:0044464 +5 more

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) pseudogene candidate

pN/pS 0.238 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 21.21% of strains (30805) · clonal

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
Ala_racemase_NPF01168.27 2.3e-0920–252 Alanine racemase, N-terminal domain

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

Closest characterised functional partner: sepF (cell division protein SepF), high confidence from genomic context alone (score 965 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2147c sepF cell division protein SepF 969 965 ctx neighborhood:831 coexpression:800
Rv2149c yfiH laccase domain-containing protein 978 960 ctx neighborhood:882 coexpression:672 textmining:496
Rv2150c ftsZ cell division protein FtsZ 901 892 ctx neighborhood:879
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 793 793 ctx neighborhood:597 coexpression:508
Rv2146c transmembrane protein 812 782 ctx neighborhood:571 coexpression:513
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 772 772 ctx neighborhood:713
Rv2145c wag31 cell wall synthesis protein Wag31 745 729 ctx neighborhood:423 coexpression:549
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 724 706 ctx neighborhood:678
Rv2151c ftsQ cell division protein FtsQ 704 687 ctx neighborhood:677
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 645 646 ctx neighborhood:597
Rv2154c ftsW lipid II flippase FtsW 651 630 ctx neighborhood:608
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 653 600 ctx neighborhood:597
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 621 588 ctx neighborhood:559
Rv2927c sepIVA hyp hypothetical protein 597 572 coexpression:547
Rv1712 cmk cytidylate kinase 548 548 coexpression:448

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: YggS family pyridoxal phosphate-dependent enzyme
  • Pfam (hmmscan --cut_ga): Ala_racemase_N PF01168.27 (E=2e-09)
  • (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_216664.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ala_racemase_N (PF01168.27)
  • 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 COG0325
  • Curated reference: UniProt P9WFQ7 (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 — 29 functional partner(s); context anchor sepF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002284|Rv2148c|
MAADLSAYPDRESELTHALAAMRSRLAAAAEAAGRNVGEIELLPITKFFPATDVAILFRLGCRSVGESREQEASAKMAELNRLLAAAELGHSGGVHWHMVGRIQRNKAGSLARWAHTAHSVDSSRLVTALDRAVVAALAEHRRGERLRVYVQVSLDGDGSRGGVDSTTPGAVDRICAQVQESEGLELVGLMGIPPLDWDPDEAFDRLQSEHNRVRAMFPHAIGLSAGMSNDLEVAVKHGSTCVRVGTALLGPRRLRSP