mshC Resolved · high auto-curated

H37Rv Rv2130c · MTBC0 mtbc0_002263 · 414 aa · 2418478–2419722 (-) · RefSeq NP_216646.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase
MTBC0 PGAP re-annotationcysteine--1-D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase
Revised (this work)Cysteine--1-D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase. Pfam: tRNA-synt_1e (PF01406.26).

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

Curated reference (UniProt)

UniProt P9WJM9 SwissProt · reviewed · Evidence at protein level
UniProt nameL-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase
EC (curated) EC 6.3.1.13
Curated functionCatalyzes the ATP-dependent condensation of GlcN-Ins and L-cysteine to form L-Cys-GlcN-Ins.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namemshC
eggNOG descriptionCatalyzes the ATP-dependent condensation of GlcN-Ins and L-cysteine to form L-Cys-GlcN-Ins
Orthologous groupCOG0215
EC number EC 6.1.1.16, EC 6.3.1.13
KEGG orthology K01883, K15526
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (95) GO:0000166, GO:0003674, GO:0003824, GO:0004812, GO:0004817, GO:0005488, GO:0005524, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +83 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 0.555 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
tRNA-synt_1ePF01406.26 5.0e-8336–338 tRNA synthetases class I (C) catalytic domain

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

Closest characterised functional partner: cysQ (3'(2'),5'-bisphosphate nucleotidase CysQ), high confidence from genomic context alone (score 814 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2131c cysQ 3'(2'),5'-bisphosphate nucleotidase CysQ 823 814 ctx neighborhood:805
Rv2335 cysE serine acetyltransferase 816 792 coexpression:720
Rv0819 mshD mycothiol acetyltransferase 989 777 ctx cooccurence:549 database:500 textmining:955
Rv2133c hyp hypothetical protein 748 738 ctx neighborhood:544 cooccurence:416
Rv2134c hyp hypothetical protein 723 723 ctx neighborhood:544
Rv2129c oxidoreductase 721 721 ctx neighborhood:707
Rv1170 mshB 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase 986 704 database:500 textmining:955
Rv1976c hyp hypothetical protein 706 700 coexpression:683
Rv2614c thrS threonine--tRNA ligase 726 690 ctx cooccurence:594
Rv2466c hyp hypothetical protein 694 683 ctx cooccurence:666
Rv2135c hyp hypothetical protein 675 676 ctx neighborhood:544
Rv2555c alaS alanine--tRNA ligase 707 668 coexpression:417
Rv3834c serS serine--tRNA ligase 653 606 ctx cooccurence:471
Rv1082 mca mycothiol S-conjugate amidase 941 594 ctx cooccurence:563 textmining:862
Rv0041 leuS leucine--tRNA ligase 634 585 coexpression:415

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: cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase
  • MTBC0 PGAP product: cysteine--1-D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase
  • Pfam (hmmscan --cut_ga): tRNA-synt_1e PF01406.26 (E=5e-83)
  • (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_216646.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1e (PF01406.26)
  • 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 COG0215
  • Curated reference: UniProt P9WJM9 (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 — 82 functional partner(s); context anchor cysQ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002263|Rv2130c|mshC
MQSWYCPPVPVLPGRGPQLRLYDSADRQVRPVAPGSKATMYVCGITPYDATHLGHAATYVTFDLIHRLWLDLGHELHYVQNITDIDDPLFERADRDGVDWRDLAQAEVALFCEDMAALRVLPPQDYVGATEAIAEMVELIEKMLACGAAYVIDREMGEYQDIYFRADATLQFGYESGYDRDTMLRLCEERGGDPRRPGKSDELDALLWRAARPGEPSWPSPFGPGRPGWHVECAAIALSRIGSGLDIQGGGSDLIFPHHEFTAAHAECVSGERRFARHYVHAGMIGWDGHKMSKSRGNLVLVSALRAQDVEPSAVRLGLLAGHYRADRFWSQQVLDEATARLHRWRTATALPAGPAAVDVVARVRRYLADDLDTPKAIAALDGWVTDAVEYGGHDAGAPKLVATAIDALLGVDL