hisE Resolved · high auto-curated

H37Rv Rv2122c · MTBC0 - · 93 aa · 2380663–2380944 (-) · RefSeq YP_177860.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphoribosyl-ATP pyrophosphatase
MTBC0 PGAP re-annotation
Revised (this work)Phosphoribosyl-ATP pyrophosphatase. Pfam: PRA-PH (PF01503.23), MazG (PF03819.23).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WMM9 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphoribosyl-ATP pyrophosphatase
EC (curated) EC 3.6.1.31

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namehisE
eggNOG descriptionPhosphoribosyl-ATP
Orthologous groupCOG0140
EC number EC 3.6.1.31
KEGG orthology K01523
KEGG pathways map00340, map01100, map01110, map01230
KEGG modules M00026
Gene Ontology (25) GO:0000287, GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0009605, GO:0009607, GO:0030312, GO:0040007, GO:0043167 +13 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 0.167 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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
PRA-PHPF01503.23 5.2e-1012–93 Phosphoribosyl-ATP pyrophosphohydrolase
MazGPF03819.23 3.2e-0539–92 MazG nucleotide pyrophosphohydrolase domain

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

Closest characterised functional partner: hisG (ATP phosphoribosyltransferase), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2121c hisG ATP phosphoribosyltransferase 999 999 ctx neighborhood:882 cooccurence:713 coexpression:859 database:900 textmining:937
Rv1606 hisI phosphoribosyl-AMP cyclohydrolase 992 990 coexpression:857 database:900
Rv1605 hisF imidazole glycerol phosphate synthase subunit HisF 965 891 coexpression:857 textmining:694
Rv1599 hisD histidinol dehydrogenase 965 890 coexpression:852 textmining:704
Rv1602 hisH imidazole glycerol phosphate synthase subunit HisH 943 889 coexpression:857 textmining:517
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 963 886 coexpression:857 textmining:693
Rv1601 hisB imidazole glycerol-phosphate dehydratase 981 885 coexpression:857 textmining:848
Rv1600 hisC1 histidinol-phosphate aminotransferase 858 809 coexpression:685
Rv3772 hisC2 histidinol-phosphate aminotransferase 726 696 coexpression:685
Rv2231c cobC aminotransferase 726 696 coexpression:685
Rv2120c integral membrane protein 682 682 ctx neighborhood:679
Rv0828c deaminase 640 627 coexpression:627
Rv3114 hyp hypothetical protein 638 625 coexpression:625
Rv3752c tadA cytidine/deoxycytidylate deaminase 638 625 coexpression:625
Rv3859c gltB glutamate synthase large subunit 648 611 ctx neighborhood:544

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): phosphoribosyl-ATP pyrophosphatase
  • Pfam (hmmscan --cut_ga): PRA-PH PF01503.23 (E=5e-10), MazG PF03819.23 (E=3e-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 YP_177860.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PRA-PH (PF01503.23), MazG (PF03819.23)
  • 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 COG0140
  • Curated reference: UniProt P9WMM9 (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 — 50 functional partner(s); context anchor hisG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2122c|hisE
MQQSLAVKTFEDLFAELGDRARTRPADSTTVAALDGGVHALGKKLLEEAGEVWLAAEHESNDALAEEISQLLYWTQVLMISRGLSLDDVYRKL