glmU Resolved · high auto-curated

H37Rv Rv1018c · MTBC0 mtbc0_001093 · 495 aa · 1143910–1145397 (-) · RefSeq NP_215534.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase
MTBC0 PGAP re-annotationbifunctional UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase GlmU
Revised (this work)Bifunctional UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase GlmU. Pfam: IspD (PF01128.26), NTP_transf_3 (PF12804.14), NTP_transferase (PF00483.30), Hexapep (PF00132.31).

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

Curated reference (UniProt)

UniProt P9WMN3 SwissProt · reviewed · Evidence at protein level
UniProt nameBifunctional protein GlmU [Includes: UDP-N-acetylglucosamine pyrophosphorylase
EC (curated) EC 2.3.1.157, EC 2.7.7.23
Curated functionCatalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameglmU
eggNOG descriptionCatalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP- GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5- monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain
Orthologous groupCOG1207
EC number EC 2.3.1.157, EC 2.7.7.23
KEGG orthology K04042
KEGG pathways map00520, map01100, map01130
KEGG modules M00362
Gene Ontology (32) GO:0000287, GO:0003674, GO:0003824, GO:0003977, GO:0005488, GO:0008080, GO:0008150, GO:0016407, GO:0016410, GO:0016740, GO:0016746, GO:0016747 +20 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 0.871 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
IspDPF01128.26 4.8e-118–225 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
NTP_transf_3PF12804.14 3.1e-189–142 MobA-like NTP transferase domain
NTP_transferasePF00483.30 4.7e-1710–231 Nucleotidyl transferase
HexapepPF00132.31 2.9e-06277–311 Bacterial transferase hexapeptide (six repeats)

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

Closest characterised functional partner: prsA (ribose-phosphate pyrophosphokinase), high confidence from genomic context alone (score 960 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1017c prsA ribose-phosphate pyrophosphokinase 969 960 ctx neighborhood:778 cooccurence:442 coexpression:700
Rv3441c mrsA phosphoglucosamine mutase 993 948 ctx cooccurence:465 database:900 textmining:879
Rv1315 murA UDP-N-acetylglucosamine 1-carboxyvinyltransferase 977 921 database:900 textmining:730
Rv0408 pta phosphate acetyltransferase 968 838 experimental:810 textmining:812
Rv3436c glmS glucosamine--fructose-6-phosphate aminotransferase 962 823 ctx fusion:590 coexpression:464 textmining:798
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 926 773 ctx fusion:748 textmining:692
Rv1016c lpqT lipoprotein LpqT 748 749 ctx neighborhood:747
Rv1302 rfe decaprenyl-phosphate N-acetylglucosaminephosphotransferase 647 608 database:500
Rv1307 atpH ATP synthase subunit b/delta 569 554 coexpression:414
Rv3859c gltB glutamate synthase large subunit 545 545 ctx neighborhood:544
Rv2883c pyrH uridylate kinase 578 508
Rv1019 transcriptional regulator 492 492 ctx neighborhood:492
Rv1020 mfd transcription-repair coupling factor 514 490 ctx neighborhood:486
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 871 487 ctx fusion:441 textmining:760
Rv2845c proS proline--tRNA ligase 486 487 ctx cooccurence:439

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: bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase
  • MTBC0 PGAP product: bifunctional UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase GlmU
  • Pfam (hmmscan --cut_ga): IspD PF01128.26 (E=5e-11), NTP_transf_3 PF12804.14 (E=3e-18), NTP_transferase PF00483.30 (E=5e-17), Hexapep PF00132.31 (E=3e-06)
  • (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_215534.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IspD (PF01128.26), NTP_transf_3 (PF12804.14), NTP_transferase (PF00483.30), Hexapep (PF00132.31)
  • 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 COG1207
  • Curated reference: UniProt P9WMN3 (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 — 60 functional partner(s); context anchor prsA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001093|Rv1018c|glmU
MTFPGDTAVLVLAAGPGTRMRSDTPKVLHTLAGRSMLSHVLHAIAKLAPQRLIVVLGHDHQRIAPLVGELADTLGRTIDVALQDRPLGTGHAVLCGLSALPDDYAGNVVVTSGDTPLLDADTLADLIATHRAVSAAVTVLTTTLDDPFGYGRILRTQDHEVMAIVEQTDATPSQREIREVNAGVYAFDIAALRSALSRLSSNNAQQELYLTDVIAILRSDGQTVHASHVDDSALVAGVNNRVQLAELASELNRRVVAAHQLAGVTVVDPATTWIDVDVTIGRDTVIHPGTQLLGRTQIGGRCVVGPDTTLTDVAVGDGASVVRTHGSSSSIGDGAAVGPFTYLRPGTALGADGKLGAFVEVKNSTIGTGTKVPHLTYVGDADIGEYSNIGASSVFVNYDGTSKRRTTVGSHVRTGSDTMFVAPVTIGDGAYTGAGTVVREDVPPGALAVSAGPQRNIENWVQRKRPGSPAAQASKRASEMACQQPTQPPDADQTP