murD Resolved · high auto-curated
H37Rv Rv2155c · MTBC0 mtbc0_002291 ·
486 aa · 2442313–2443773 (-) ·
RefSeq NP_216671.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | UDP-N-acetylmuramoylalanine--D-glutamate ligase |
|---|---|
| MTBC0 PGAP re-annotation | UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase |
| Revised (this work) | UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase. Pfam: 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 |
P9WJL5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | UDP-N-acetylmuramoylalanine--D-glutamate ligase |
| EC (curated) |
EC 6.3.2.9
|
| Curated function | Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | murD |
| eggNOG description | Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA) |
| Orthologous group | COG0771 |
| EC number |
EC 6.3.2.9
|
| KEGG orthology |
K01925
|
| KEGG pathways |
map00471, map00550, map01100
|
| Gene Ontology (10) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0040007, GO:0044424, GO:0044444, GO:0044464
|
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 | 0.799 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 14 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Mur_ligase_M | PF08245.19 | 7.1e-19 | 118–290 | Mur ligase middle domain |
Mur_ligase_C | PF02875.27 | 3.4e-07 | 313–461 | Mur ligase, glutamate ligase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: murG (UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2153c murG |
UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase | 999 | 999 ctx | neighborhood:876 cooccurence:713 coexpression:968 textmining:894 |
Rv2157c murF |
UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase | 999 | 998 ctx | neighborhood:881 cooccurence:712 coexpression:942 textmining:957 |
Rv2152c murC |
UDP-N-acetylmuramate--alanine ligase | 999 | 998 ctx | neighborhood:876 coexpression:779 database:900 textmining:795 |
Rv2158c murE |
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase | 998 | 996 ctx | neighborhood:881 coexpression:570 database:900 textmining:746 |
Rv2156c murX |
phospho-N-acetylmuramoyl-pentappeptidetransferase | 996 | 991 ctx | neighborhood:881 cooccurence:695 coexpression:780 textmining:649 |
Rv2151c ftsQ |
cell division protein FtsQ | 992 | 983 ctx | neighborhood:876 coexpression:865 textmining:608 |
Rv2154c ftsW |
lipid II flippase FtsW | 992 | 972 ctx | neighborhood:876 cooccurence:472 coexpression:607 textmining:741 |
Rv1338 murI |
glutamate racemase | 994 | 957 ctx | cooccurence:550 database:900 textmining:878 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase | 902 | 902 | database:900 |
Rv2163c pbpB |
penicillin-binding membrane protein PbpB | 937 | 854 ctx | neighborhood:544 cooccurence:535 textmining:588 |
Rv2981c ddlA |
D-alanine--D-alanine ligase | 959 | 765 | coexpression:639 textmining:834 |
Rv2160A |
Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266 | 756 | 756 ctx | neighborhood:712 |
Rv2159c hyp |
hypothetical protein | 730 | 730 ctx | neighborhood:709 |
Rv2150c ftsZ |
cell division protein FtsZ | 923 | 719 ctx | neighborhood:561 textmining:738 |
Rv1302 rfe |
decaprenyl-phosphate N-acetylglucosaminephosphotransferase | 748 | 714 | coexpression:698 |
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-acetylmuramoylalanine--D-glutamate ligase
- MTBC0 PGAP product: UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase
- Pfam (hmmscan --cut_ga): Mur_ligase_M PF08245.19 (E=7e-19), Mur_ligase_C PF02875.27 (E=3e-07)
- (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_216671.3)
- Domains: Pfam-A via hmmscan --cut_ga — 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
COG0771 - Curated reference: UniProt P9WJL5 (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 —
64 functional partner(s); context anchor
murG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002291|Rv2155c|murD MLDPLGPGAPVLVAGGRVTGQAVAAVLTRFGATPTVCDDDPVMLRPHAERGLPTVSSSDAVQQITGYALVVASPGFSPATPLLAAAAAAGVPIWGDVELAWRLDAAGCYGPPRSWLVVTGTNGKTTTTSMLHAMLIAGGRRAVLCGNIGSAVLDVLDEPAELLAVELSSFQLHWAPSLRPEAGAVLNIAEDHLDWHATMAEYTAAKARVLTGGVAVAGLDDSRAAALLDGSPAQVRVGFRLGEPAAGELGVRDAHLVDRAFSDDLTLLPVASIPVPGPVGVLDALAAAALARSVGVPAGAIADAVTSFRVGRHRAEVVAVADGITYVDDSKATNPHAARASVLAYPRVVWIAGGLLKGASLHAEVAAMASRLVGAVLIGRDRAAVAEALSRHAPDVPVVQVVAGEDTGMPATVEVPVACVLDVAKDDKAGETVGAAVMTAAVAAARRMAQPGDTVLLAPAGASFDQFTGYADRGEAFATAVRAVIR