murC Resolved · high auto-curated

H37Rv Rv2152c · MTBC0 mtbc0_002288 · 494 aa · 2438017–2439501 (-) · RefSeq NP_216668.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)UDP-N-acetylmuramate--alanine ligase
MTBC0 PGAP re-annotationUDP-N-acetylmuramate--L-alanine ligase
Revised (this work)UDP-N-acetylmuramate--L-alanine ligase. Pfam: Mur_ligase (PF01225.31), Mur_ligase_M (PF08245.19), Mur_ligase_C (PF02875.27).

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

Curated reference (UniProt)

UniProt P9WJL7 SwissProt · reviewed · Evidence at protein level
UniProt nameUDP-N-acetylmuramate--L-alanine ligase
EC (curated) EC 6.3.2.8
Curated functionCell wall formation.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namemurC
eggNOG descriptionBelongs to the MurCDEF family
Orthologous groupCOG0773
EC number EC 6.3.2.8
KEGG orthology K01924
KEGG pathways map00471, map00550, map01100
Gene Ontology (38) GO:0000270, GO:0003674, GO:0003824, GO:0006022, GO:0006023, GO:0006024, GO:0006807, GO:0008150, GO:0008152, GO:0008763, GO:0009058, GO:0009059 +26 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)

pN/pS 0.268 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 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
Mur_ligasePF01225.31 2.2e-2413–115 Mur ligase family, catalytic domain
Mur_ligase_MPF08245.19 1.6e-24120–309 Mur ligase middle domain
Mur_ligase_CPF02875.27 1.9e-19331–465 Mur ligase, glutamate ligase domain

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

Closest characterised functional partner: murD (UDP-N-acetylmuramoylalanine--D-glutamate ligase), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 999 998 ctx neighborhood:876 coexpression:779 database:900 textmining:795
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 999 996 ctx neighborhood:882 cooccurence:658 coexpression:918 textmining:879
Rv2154c ftsW lipid II flippase FtsW 998 995 ctx neighborhood:881 cooccurence:682 coexpression:876 textmining:753
Rv2151c ftsQ cell division protein FtsQ 997 992 ctx neighborhood:881 coexpression:932 textmining:683
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 992 981 ctx neighborhood:876 cooccurence:732 coexpression:470 textmining:638
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 995 977 ctx neighborhood:876 fusion:582 coexpression:423 textmining:799
Rv2981c ddlA D-alanine--D-alanine ligase 993 973 ctx fusion:887 cooccurence:470 coexpression:555 textmining:783
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 993 969 ctx neighborhood:876 coexpression:666 textmining:798
Rv0482 murB UDP-N-acetylenolpyruvoylglucosamine reductase 993 944 database:900 textmining:888
Rv2163c pbpB penicillin-binding membrane protein PbpB 953 889 ctx neighborhood:544 cooccurence:711 textmining:603
Rv2149c yfiH laccase domain-containing protein 803 804 ctx neighborhood:734
Rv2150c ftsZ cell division protein FtsZ 953 795 ctx neighborhood:566 textmining:784
Rv1315 murA UDP-N-acetylglucosamine 1-carboxyvinyltransferase 987 780 ctx cooccurence:727 textmining:948
Rv2148c hyp hypothetical protein 772 772 ctx neighborhood:713
Rv1713 engA GTPase Der 781 757 coexpression:738

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: UDP-N-acetylmuramate--alanine ligase
  • MTBC0 PGAP product: UDP-N-acetylmuramate--L-alanine ligase
  • Pfam (hmmscan --cut_ga): Mur_ligase PF01225.31 (E=2e-24), Mur_ligase_M PF08245.19 (E=2e-24), Mur_ligase_C PF02875.27 (E=2e-19)
  • (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_216668.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Mur_ligase (PF01225.31), Mur_ligase_M (PF08245.19), Mur_ligase_C (PF02875.27)
  • 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 COG0773
  • Curated reference: UniProt P9WJL7 (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 — 83 functional partner(s); context anchor murD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002288|Rv2152c|murC
MSTEQLPPDLRRVHMVGIGGAGMSGIARILLDRGGLVSGSDAKESRGVHALRARGALIRIGHDASSLDLLPGGATAVVTTHAAIPKTNPELVEARRRGIPVVLRPAVLAKLMAGRTTLMVTGTHGKTTTTSMLIVALQHCGLDPSFAVGGELGEAGTNAHHGSGDCFVAEADESDGSLLQYTPHVAVITNIESDHLDFYGSVEAYVAVFDSFVERIVPGGALVVCTDDPGGAALAQRATELGIRVLRYGSVPGETMAATLVSWQQQGVGAVAHIRLASELATAQGPRVMRLSVPGRHMALNALGALLAAVQIGAPADEVLDGLAGFEGVRRRFELVGTCGVGKASVRVFDDYAHHPTEISATLAAARMVLEQGDGGRCMVVFQPHLYSRTKAFAAEFGRALNAADEVFVLDVYGAREQPLAGVSGASVAEHVTVPMRYVPDFSAVAQQVAAAASPGDVIVTMGAGDVTLLGPEILTALRVRANRSAPGRPGVLG