Rv3400 Family assigned · medium auto-curated

H37Rv Rv3400 · MTBC0 mtbc0_003613 · 262 aa · 3842678–3843466 (+) · RefSeq NP_217917.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationbeta-phosphoglucomutase family hydrolase
Revised (this work)Beta-phosphoglucomutase family hydrolase. Pfam: Hydrolase (PF00702.33), HAD_2 (PF13419.13).

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

Curated reference (UniProt)

UniProt P9WKZ7 SwissProt · reviewed · Evidence at protein level
UniProt nameBeta-phosphoglucomutase
EC (curated) EC 5.4.2.6
Curated functionCatalyzes the interconversion of D-glucose 1-phosphate (G1P) and D-glucose 6-phosphate (G6P), forming beta-D-glucose 1,6-(bis)phosphate (beta-G16P) as an intermediate. Does not show phosphatase and pyrophosphatase activity. Is probably one of the key enzymes involved in the metabolism of trehalose, a disaccharide abundantly present in mycobacteria and which plays a crucial role in bacterial physiology and virulence.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBeta-phosphoglucomutase family hydrolase
Orthologous groupCOG0637
Gene Ontology (6) GO:0003674, GO:0003824, GO:0008801, GO:0016853, GO:0016866, GO:0016868

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 0.528 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
HydrolasePF00702.33 8.5e-2423–225 haloacid dehalogenase-like hydrolase
HAD_2PF13419.13 7.9e-1227–231 Haloacid dehalogenase-like hydrolase

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

Closest characterised functional partner: Rv3401 (glycosyl hydrolase), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3401 glycosyl hydrolase 997 997 ctx neighborhood:865 fusion:898 cooccurence:773
Rv3396c guaA GMP synthase 785 778 ctx neighborhood:706
Rv3399 S-adenosylmethionine-dependent methyltransferase 638 638 ctx neighborhood:633
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 560 467
Rv3398c idsA1 multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase 455 456 ctx neighborhood:449
Rv3397c phyA phytoene synthase 443 423 ctx neighborhood:416
Rv3372 otsB2 trehalose 6-phosphate phosphatase 427 399
Rv3406 dioxygenase 873 70 textmining:870
Rv3405c HTH-type transcriptional regulator 870 47 textmining:870
Rv1980c mpt64 immunogenic protein Mpt64 443 47 textmining:440
Rv1984c cfp21 cutinase 442 47 textmining: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: hydrolase
  • MTBC0 PGAP product: beta-phosphoglucomutase family hydrolase
  • Pfam (hmmscan --cut_ga): Hydrolase PF00702.33 (E=9e-24), HAD_2 PF13419.13 (E=8e-12)
  • (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_217917.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Hydrolase (PF00702.33), HAD_2 (PF13419.13)
  • 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 COG0637
  • Curated reference: UniProt P9WKZ7 (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 — 11 functional partner(s); context anchor Rv3401
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003613|Rv3400|
MANWYRPNYPEVRSRVLGLPEKVRACLFDLDGVLTDTASLHTKAWKAMFDAYLAERAERTGEKFVPFDPAADYHTYVDGKKREDGVRSFLSSRAIEIPDGSPDDPGAAETVYGLGNRKNDMLHKLLRDDGAQVFDGSRRYLEAVTAAGLGVAVVSSSANTRDVLATTGLDRFVQQRVDGVTLREEHIAGKPAPDSFLRAAELLGVTPDAAAVFEDALSGVAAGRAGNFAVVVGINRTGRAAQAAQLRRHGADVVVTDLAELL