pimA Resolved · high auto-curated

H37Rv Rv2610c · MTBC0 mtbc0_002778 · 378 aa · 2961418–2962554 (-) · RefSeq NP_217126.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alpha-(1-2)-phosphatidylinositol mannosyltransferase
MTBC0 PGAP re-annotationphosphatidyl-myo-inositol alpha-mannosyltransferase
Revised (this work)Phosphatidyl-myo-inositol alpha-mannosyltransferase. Pfam: Glyco_transf_4 (PF13439.13), Glyco_trans_4_4 (PF13579.13), GT4-conflict (PF20706.4), Glycos_transf_1 (PF00534.27), Glyco_trans_1_4 (PF13692.13), Glyco_trans_1_2 (PF13524.13).

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

Curated reference (UniProt)

UniProt P9WMZ5 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphatidyl-myo-inositol mannosyltransferase
EC (curated) EC 2.4.1.345
Curated functionInvolved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIM) which are early precursors in the biosynthesis of lipomannans (LM) and lipoarabinomannans (LAM). Catalyzes the addition of a mannosyl residue from GDP-D-mannose (GDP-Man) to the position 2 of the carrier lipid phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). PimA plays an essential role for growth in macrophages and during both the acute and chronic phases of infection.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namepimA
eggNOG descriptionGDP-mannose-dependent alpha-(1-2)-phosphatidylinositol mannosyltransferase
Orthologous groupCOG0438
EC number EC 2.4.1.345
KEGG orthology K08256
CAZy family GT4
Gene Ontology (49) GO:0000026, GO:0000030, GO:0000287, GO:0003674, GO:0003824, GO:0004376, GO:0004377, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006629 +37 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 0.118 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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_transf_4PF13439.13 7.4e-2614–173 Glycosyltransferase Family 4
Glyco_trans_4_4PF13579.13 2.6e-1115–153 Glycosyl transferase 4-like domain
GT4-conflictPF20706.4 6.4e-07163–305 Family 4 Glycosyltransferase in conflict systems
Glycos_transf_1PF00534.27 3.2e-29187–344 Glycosyl transferases group 1
Glyco_trans_1_4PF13692.13 2.6e-33189–332 Glycosyl transferases group 1
Glyco_trans_1_2PF13524.13 9.5e-06216–361 Glycosyl transferase-like

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

Closest characterised functional partner: Rv2611c (phosphatidylinositol mannoside acyltransferase), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2611c phosphatidylinositol mannoside acyltransferase 999 996 ctx neighborhood:879 cooccurence:725 database:900 textmining:897
Rv2609c membrane protein 982 968 ctx neighborhood:781 cooccurence:506 coexpression:732 textmining:479
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 963 952 ctx neighborhood:879 cooccurence:510
Rv2188c pimB alpha-(1-6)-phosphatidylinositol monomannoside mannosyltransferase 952 928 database:900
Rv2613c AP-4-A phosphorylase 945 905 ctx neighborhood:879 textmining:456
Rv2614c thrS threonine--tRNA ligase 887 881 ctx neighborhood:879
Rv1326c glgB 1,4-alpha-glucan branching protein 817 783 coexpression:414 database:572
Rv1562c treZ malto-oligosyltrehalose trehalohydrolase 801 782 coexpression:411 database:572
Rv2529 hyp hypothetical protein 673 662 database:516
Rv3670 ephE epoxide hydrolase EphE 579 579 ctx cooccurence:566
Rv2614A hyp hypothetical protein 549 549 ctx neighborhood:546
Rv1698 mctB copper transporter MctB 526 527 ctx cooccurence:518
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 551 523 coexpression:444
Rv2606c snzP pyridoxine biosynthesis protein 527 515 ctx neighborhood:510
Rv3784 dTDP-glucose 4,6-dehydratase 526 502 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: alpha-(1-2)-phosphatidylinositol mannosyltransferase
  • MTBC0 PGAP product: phosphatidyl-myo-inositol alpha-mannosyltransferase
  • Pfam (hmmscan --cut_ga): Glyco_transf_4 PF13439.13 (E=7e-26), Glyco_trans_4_4 PF13579.13 (E=3e-11), GT4-conflict PF20706.4 (E=6e-07), Glycos_transf_1 PF00534.27 (E=3e-29), Glyco_trans_1_4 PF13692.13 (E=3e-33), Glyco_trans_1_2 PF13524.13 (E=1e-05)
  • (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_217126.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Glyco_transf_4 (PF13439.13), Glyco_trans_4_4 (PF13579.13), GT4-conflict (PF20706.4), Glycos_transf_1 (PF00534.27), Glyco_trans_1_4 (PF13692.13), Glyco_trans_1_2 (PF13524.13)
  • 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 P9WMZ5 (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 — 45 functional partner(s); context anchor Rv2611c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002778|Rv2610c|pimA
MRIGMICPYSFDVPGGVQSHVLQLAEVMRTRGHLVSVLAPASPHAALPDYFVSGGRAVPIPYNGSVARLRFGPATHRKVKKWLAHGDFDVLHLHEPNAPSLSMLALNIAEGPIVATFHTSTTKSLTLTVFQGILRPMHEKIVGRIAVSDLARRWQMEALGSDAVEIPNGVDVDSFASAARLDGYPRQGKTVLFLGRYDEPRKGMAVLLDALPKVVQRFPDVQLLIVGHGDADQLRGQAGRLAAHLRFLGQVDDAGKASAMRSADVYCAPNTGGESFGIVLVEAMAAGTAVVASDLDAFRRVLRDGEVGHLVPVDPPDLQAAALADGLIAVLENDVLRERYVAAGNAAVRRYDWSVVASQIMRVYETVAGSGAKVQVAS