pmmA Resolved · high auto-curated

H37Rv Rv3257c · MTBC0 mtbc0_003465 · 465 aa · 3659455–3660852 (-) · RefSeq NP_217774.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphomannomutase PmmA
MTBC0 PGAP re-annotationphosphomannomutase/phosphoglucomutase
Revised (this work)Phosphomannomutase/phosphoglucomutase. Pfam: PGM_PMM_I (PF02878.23), PGM_PMM_II (PF02879.23), PGM_PMM_III (PF02880.23), PGM_PMM_IV (PF00408.27).

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

Curated reference (UniProt)

UniProt O86374 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable phosphomannomutase PmmA

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namemanB
eggNOG descriptionthe resulting product is then converted to GDP-mannose by ManC which is then used in the synthesis of mannose-containing glycoconjugates that are important for mediating entry into host cells
Orthologous groupCOG1109
EC number EC 5.4.2.8
KEGG orthology K01840
KEGG pathways map00051, map00520, map01100, map01110, map01130
KEGG modules M00114
Gene Ontology (60) GO:0000271, GO:0000287, GO:0003674, GO:0003824, GO:0004614, GO:0004615, GO:0005488, GO:0005975, GO:0005976, GO:0006082, GO:0006629, GO:0008150 +48 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 0.349 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
PGM_PMM_IPF02878.23 2.2e-3211–128 Phosphoglucomutase/phosphomannomutase, alpha/beta/alpha domain I
PGM_PMM_IIPF02879.23 9.6e-24160–259 Phosphoglucomutase/phosphomannomutase, alpha/beta/alpha domain II
PGM_PMM_IIIPF02880.23 1.2e-26269–373 Phosphoglucomutase/phosphomannomutase, alpha/beta/alpha domain III
PGM_PMM_IVPF00408.27 5.4e-09378–450 Phosphoglucomutase/phosphomannomutase, C-terminal domain

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

Closest characterised functional partner: manA (mannose-6-phosphate isomerase), high confidence from genomic context alone (score 990 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3255c manA mannose-6-phosphate isomerase 994 990 ctx neighborhood:882 database:900 textmining:417
Rv3264c manB D-alpha-D-mannose-1-phosphate guanylyltransferase ManB 967 951 coexpression:435 database:900
Rv3308 pmmB phosphomannomutase PmmB 914 901 database:900
Rv3256c hyp hypothetical protein 902 896 ctx neighborhood:881
Rv1328 glgP glycogen phosphorylase 752 725 ctx fusion:672
Rv3259 hyp hypothetical protein 704 704 ctx neighborhood:658
Rv0993 galU UTP--glucose-1-phosphate uridylyltransferase 668 633 ctx fusion:532
Rv3258c hyp hypothetical protein 629 630 ctx neighborhood:618
Rv2101 helZ helicase HelZ 473 452 database:416
Rv2228c multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase 496 449
Rv1326c glgB 1,4-alpha-glucan branching protein 478 446 coexpression:427
Rv1562c treZ malto-oligosyltrehalose trehalohydrolase 477 444 coexpression:425
Rv0486 mshA D-inositol 3-phosphate glycosyltransferase 447 421
Rv0707 rpsC 30S ribosomal protein S3 433 412
Rv1202 dapE succinyl-diaminopimelate desuccinylase DapE 430 396

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: phosphomannomutase PmmA
  • MTBC0 PGAP product: phosphomannomutase/phosphoglucomutase
  • Pfam (hmmscan --cut_ga): PGM_PMM_I PF02878.23 (E=2e-32), PGM_PMM_II PF02879.23 (E=1e-23), PGM_PMM_III PF02880.23 (E=1e-26), PGM_PMM_IV PF00408.27 (E=5e-09)
  • (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_217774.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PGM_PMM_I (PF02878.23), PGM_PMM_II (PF02879.23), PGM_PMM_III (PF02880.23), PGM_PMM_IV (PF00408.27)
  • 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 COG1109
  • Curated reference: UniProt O86374 (TrEMBL, unreviewed; 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 — 20 functional partner(s); context anchor manA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003465|Rv3257c|pmmA
MSWPAAAVDRVIKAYDVRGLVGEEIDESLVTDLGAAFARLMRTEDARPVVIGHDMRDSSPSLADAFAAGVTGQGLDVVRVGLASTDQLYFASGLLDCPGAMFTASHNPAAYNGIKMCRAAAKPVGADTGLTAIRDDLIAGVARYDGTPGTIADQDVLVDYGAFLRSLVDTSGLRPLRVAVDAGNGMAGHTAPAVLGVIDSITLLPLYFELDGSFPNHEANPLDPANLVDLQAYVRDTGADIGLAFDGDADRCFVVDERGQPVSPSTVTALVAARELNREIGATIIHNVITSRAVPELVAERGGTPLRSRVGHSYIKALMAETGAIFGGEHSAHYYFRDFWGADSGMLAALHVLAALGEQSRPLSELTADYQRYESSGEINFTVVDSSACVEAVLKSFGNRIVSIDHLDGVTVDLGDDSWFNLRSSNTEPLLRLNVEGRSVGDVDAVVRQVSAEIAAQSAHAKAGP