murE Resolved · high auto-curated

H37Rv Rv2158c · MTBC0 mtbc0_002294 · 535 aa · 2446380–2447987 (-) · RefSeq NP_216674.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
MTBC0 PGAP re-annotationUDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2%2C6-diaminopimelate ligase
Revised (this work)UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2%2C6-diaminopimelate 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 P9WJL3 SwissProt · reviewed · Evidence at protein level
UniProt nameUDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase
EC (curated) EC 6.3.2.13
Curated functionCatalyzes the addition of meso-diaminopimelic acid to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namemurE
eggNOG descriptionCatalyzes the addition of meso-diaminopimelic acid to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan
Orthologous groupCOG0769
EC number EC 6.3.2.13
KEGG orthology K01928
KEGG pathways map00300, map00550
Gene Ontology (48) GO:0000270, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006022, GO:0006023, GO:0006024 +36 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 0.552 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 7 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 8.8e-0862–137 Mur ligase family, catalytic domain
Mur_ligase_MPF08245.19 2.0e-48151–354 Mur ligase middle domain
Mur_ligase_CPF02875.27 4.1e-34376–504 Mur ligase, glutamate ligase domain

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

Closest characterised functional partner: murF (UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 999 1000 ctx neighborhood:881 fusion:899 coexpression:712 database:900 textmining:803
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 998 996 ctx neighborhood:881 coexpression:570 database:900 textmining:746
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 997 980 ctx neighborhood:876 cooccurence:664 coexpression:430 textmining:855
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 991 980 ctx neighborhood:881 cooccurence:714 coexpression:473 textmining:599
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 995 977 ctx neighborhood:876 fusion:582 coexpression:423 textmining:799
Rv2154c ftsW lipid II flippase FtsW 982 944 ctx neighborhood:876 cooccurence:454 textmining:694
Rv2726c dapF diaminopimelate epimerase 979 926 database:900 textmining:730
Rv2151c ftsQ cell division protein FtsQ 963 926 ctx neighborhood:876 coexpression:425 textmining:522
Rv1293 lysA diaminopimelate decarboxylase 921 911 database:900
Rv2163c pbpB penicillin-binding membrane protein PbpB 943 875 ctx neighborhood:544 cooccurence:532 coexpression:445 textmining:565
Rv3713 cobQ2 cobyric acid synthase CobQ 922 853 experimental:817 textmining:494
Rv2159c hyp hypothetical protein 847 784 ctx neighborhood:709
Rv2160A Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266 790 776 ctx neighborhood:712
Rv1018c glmU bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase 926 773 ctx fusion:748 textmining:692
Rv2150c ftsZ cell division protein FtsZ 908 760 ctx neighborhood:561 textmining:635

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-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
  • MTBC0 PGAP product: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2%2C6-diaminopimelate ligase
  • Pfam (hmmscan --cut_ga): Mur_ligase PF01225.31 (E=9e-08), Mur_ligase_M PF08245.19 (E=2e-48), Mur_ligase_C PF02875.27 (E=4e-34)
  • (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_216674.1)
  • 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 COG0769
  • Curated reference: UniProt P9WJL3 (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 — 67 functional partner(s); context anchor murF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002294|Rv2158c|murE
MSSLARGISRRRTEVATQVEAAPTGLRPNAVVGVRLAALADQVGAALAEGPAQRAVTEDRTVTGVTLRAQDVSPGDLFAALTGSTTHGARHVGDAIARGAVAVLTDPAGVAEIAGRAAVPVLVHPAPRGVLGGLAATVYGHPSERLTVIGITGTSGKTTTTYLVEAGLRAAGRVAGLIGTIGIRVGGADLPSALTTPEAPTLQAMLAAMVERGVDTVVMEVSSHALALGRVDGTRFAVGAFTNLSRDHLDFHPSMADYFEAKASLFDPDSALRARTAVVCIDDDAGRAMAARAADAITVSAADRPAHWRATDVAPTDAGGQQFTAIDPAGVGHHIGIRLPGRYNVANCLVALAILDTVGVSPEQAVPGLREIRVPGRLEQIDRGQGFLALVDYAHKPEALRSVLTTLAHPDRRLAVVFGAGGDRDPGKRAPMGRIAAQLADLVVVTDDNPRDEDPTAIRREILAGAAEVGGDAQVVEIADRRDAIRHAVAWARPGDVVLIAGKGHETGQRGGGRVRPFDDRVELAAALEALERRA