gmhA Resolved · high auto-curated

H37Rv Rv0113 · MTBC0 mtbc0_000123 · 196 aa · 137484–138074 (+) · RefSeq NP_214627.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphoheptose isomerase
MTBC0 PGAP re-annotationD-sedoheptulose 7-phosphate isomerase
Revised (this work)D-sedoheptulose 7-phosphate isomerase. Pfam: SIS_2 (PF13580.12), SIS (PF01380.28).

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

Curated reference (UniProt)

UniProt P9WGG1 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphoheptose isomerase
EC (curated) EC 5.3.1.28
Curated functionCatalyzes the isomerization of sedoheptulose 7-phosphate in D-glycero-D-manno-heptose 7-phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namegmhA
eggNOG descriptionCatalyzes the isomerization of sedoheptulose 7-phosphate in D-glycero-D-manno-heptose 7-phosphate
Orthologous groupCOG0279
EC number EC 2.7.7.71, EC 5.3.1.28
KEGG orthology K03271, K15669
KEGG pathways map00540, map01100
KEGG modules M00064

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) pseudogene candidate

pN/pS 1.017 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 2.71% of strains (3931) · clonal

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
SIS_2PF13580.12 1.4e-2435–148 SIS domain
SISPF01380.28 1.2e-08111–166 SIS domain

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

Closest characterised functional partner: hddA (D-alpha-D-heptose-7-phosphate kinase HddA), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0115 hddA D-alpha-D-heptose-7-phosphate kinase HddA 998 999 ctx neighborhood:710 cooccurence:736 coexpression:811 database:900
Rv0114 gmhB D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase 999 993 ctx neighborhood:713 cooccurence:774 coexpression:907 textmining:895
Rv0112 gca GDP-mannose 4,6-dehydratase 954 952 ctx neighborhood:579 coexpression:863
Rv0486 mshA D-inositol 3-phosphate glycosyltransferase 800 788 ctx fusion:776
Rv3032 glycogen synthase 566 539 ctx fusion:510
Rv0001 dnaA chromosomal replication initiator protein DnaA 554 495 experimental:469
Rv3465 rmlC dTDP-4-dehydrorhamnose 3,5-epimerase 469 391
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 431 238
Rv1514c glycosyltransferase 542 186 textmining:461
Rv2965c kdtB phosphopantetheine adenylyltransferase 824 116 textmining:809
Rv2538c aroB 3-dehydroquinate synthase 560 63 textmining:550
Rv0059 darT hyp hypothetical protein 554 55 textmining:548
Rv0033 acpA acyl carrier protein AcpA 628 49 textmining:625
Rv1564c treX maltooligosyl trehalose synthase 414 46 textmining:411
Rv2732c transmembrane protein 625 42 textmining:625

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: phosphoheptose isomerase
  • MTBC0 PGAP product: D-sedoheptulose 7-phosphate isomerase
  • Pfam (hmmscan --cut_ga): SIS_2 PF13580.12 (E=1e-24), SIS PF01380.28 (E=1e-08)
  • (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_214627.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SIS_2 (PF13580.12), SIS (PF01380.28)
  • 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 COG0279
  • Curated reference: UniProt P9WGG1 (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 — 17 functional partner(s); context anchor hddA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000123|Rv0113|gmhA
MCTARTAEEIFVETIAVKTRILNDRVLLEAARAIGDRLIAGYRAGARVFMCGNGGSAADAQHFAAELTGHLIFDRPPLGAEALHANSSHLTAVANDYDYDTVFARALEGSARPGDTLFAISTSGNSMSVLRAAKTARELGVTVVAMTGESGGQLAEFADFLINVPSRDTGRIQESHIVFIHAISEHVEHALFAPRQ