mshA Resolved · high auto-curated

H37Rv Rv0486 · MTBC0 mtbc0_000511 · 480 aa · 578713–580155 (+) · RefSeq NP_215000.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)D-inositol 3-phosphate glycosyltransferase
MTBC0 PGAP re-annotationD-inositol-3-phosphate glycosyltransferase
Revised (this work)D-inositol-3-phosphate glycosyltransferase. Pfam: Glyco_trans_4_4 (PF13579.13), Glyco_transf_4 (PF13439.13), GT4-conflict (PF20706.4), Glycos_transf_1 (PF00534.27), Glyco_trans_1_4 (PF13692.13).

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

Curated reference (UniProt)

UniProt P9WMY7 SwissProt · reviewed · Evidence at protein level
UniProt nameD-inositol 3-phosphate glycosyltransferase
EC (curated) EC 2.4.1.250
Curated functionCatalyzes the transfer of an N-acetyl-glucosamine moiety to 1D-myo-inositol 3-phosphate to produce 1D-myo-inositol 2-acetamido-2-deoxy-glucopyranoside 3-phosphate in the mycothiol (MSH) biosynthesis pathway. MSH and WhiB3 are probably part of a regulatory circuit that mediates gene expression upon acid stress (like that found in host macrophage phagosomes). MSH is one of the major redox buffers which protects bacteria against redox stressors and antibiotics; loss of MSH or ergothioneine (ERG, the other major redox buffer in this bacteria) leads to respiratory alterations and bioenergetic defic.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namemshA
eggNOG descriptionCatalyzes the transfer of a N-acetyl-glucosamine moiety to 1D-myo-inositol 3-phosphate to produce 1D-myo-inositol 2- acetamido-2-deoxy-glucopyranoside 3-phosphate in the mycothiol biosynthesis pathway
Orthologous groupCOG0438
EC number EC 2.4.1.250
KEGG orthology K15521
Gene Ontology (35) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006790, GO:0008150, GO:0008152, GO:0008194, GO:0008375 +23 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 0.449 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
Glyco_trans_4_4PF13579.13 2.7e-3266–241 Glycosyl transferase 4-like domain
Glyco_transf_4PF13439.13 1.3e-2666–245 Glycosyltransferase Family 4
GT4-conflictPF20706.4 1.7e-16136–437 Family 4 Glycosyltransferase in conflict systems
Glycos_transf_1PF00534.27 1.3e-36252–407 Glycosyl transferases group 1
Glyco_trans_1_4PF13692.13 4.3e-27266–406 Glycosyl transferases group 1

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

Closest characterised functional partner: mshB (1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase), high confidence from genomic context alone (score 797 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0487 hyp hypothetical protein 898 898 ctx neighborhood:882
Rv1170 mshB 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase 986 797 ctx fusion:471 cooccurence:602 textmining:935
Rv0113 gmhA phosphoheptose isomerase 800 788 ctx fusion:776
Rv1326c glgB 1,4-alpha-glucan branching protein 815 781 coexpression:407 database:572
Rv1562c treZ malto-oligosyltrehalose trehalohydrolase 800 781 coexpression:407 database:572
Rv0485 transcriptional regulator 728 718 ctx neighborhood:718
Rv0490 senX3 two component sensor histidine kinase SenX3 706 696 ctx neighborhood:622
Rv1082 mca mycothiol S-conjugate amidase 919 692 ctx cooccurence:668 textmining:748
Rv0491 regX3 two component sensory transduction protein RegX 689 678 ctx neighborhood:604
Rv0046c ino1 inositol-3-phosphate synthase 690 672 database:500
Rv2529 hyp hypothetical protein 673 661 database:516
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 671 658 ctx neighborhood:654
Rv0819 mshD mycothiol acetyltransferase 972 610 ctx cooccurence:610 textmining:932
Rv2466c hyp hypothetical protein 628 552 ctx cooccurence:552
Rv3264c manB D-alpha-D-mannose-1-phosphate guanylyltransferase ManB 536 507

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: D-inositol 3-phosphate glycosyltransferase
  • MTBC0 PGAP product: D-inositol-3-phosphate glycosyltransferase
  • Pfam (hmmscan --cut_ga): Glyco_trans_4_4 PF13579.13 (E=3e-32), Glyco_transf_4 PF13439.13 (E=1e-26), GT4-conflict PF20706.4 (E=2e-16), Glycos_transf_1 PF00534.27 (E=1e-36), Glyco_trans_1_4 PF13692.13 (E=4e-27)
  • (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_215000.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Glyco_trans_4_4 (PF13579.13), Glyco_transf_4 (PF13439.13), GT4-conflict (PF20706.4), Glycos_transf_1 (PF00534.27), Glyco_trans_1_4 (PF13692.13)
  • 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 COG0438
  • Curated reference: UniProt P9WMY7 (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 — 62 functional partner(s); context anchor mshB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000511|Rv0486|mshA
MAGVRHDDGSGLIAQRRPVRGEGATRSRGPSGPSNRNVSAADDPRRVALLAVHTSPLAQPGTGDAGGMNVYMLQSALHLARRGIEVEIFTRATASADPPVVRVAPGVLVRNVVAGPFEGLDKYDLPTQLCAFAAGVLRAEAVHEPGYYDIVHSHYWLSGQVGWLARDRWAVPLVHTAHTLAAVKNAALADGDGPEPPLRTVGEQQVVDEADRLIVNTDDEARQVISLHGADPARIDVVHPGVDLDVFRPGDRRAARAALGLPVDERVVAFVGRIQPLKAPDIVLRAAAKLPGVRIIVAGGPSGSGLASPDGLVRLADELGISARVTFLPPQSHTDLATLFRAADLVAVPSYSESFGLVAVEAQACGTPVVAAAVGGLPVAVRDGITGTLVSGHEVGQWADAIDHLLRLCAGPRGRVMSRAAARHAATFSWENTTDALLASYRRAIGEYNAERQRRGGEVISDLVAVGKPRHWTPRRGVGA