hisI Resolved · high auto-curated

H37Rv Rv1606 · MTBC0 mtbc0_001712 · 115 aa · 1817617–1817964 (+) · RefSeq NP_216638.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphoribosyl-AMP cyclohydrolase
MTBC0 PGAP re-annotationphosphoribosyl-AMP cyclohydrolase
Revised (this work)Phosphoribosyl-AMP cyclohydrolase. Pfam: PRA-CH (PF01502.24).

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

Curated reference (UniProt)

UniProt P9WMM7 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphoribosyl-AMP cyclohydrolase
EC (curated) EC 3.5.4.19
Curated functionCatalyzes the hydrolysis of the adenine ring of phosphoribosyl-AMP.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namehisI
eggNOG descriptionCatalyzes the hydrolysis of the adenine ring of phosphoribosyl-AMP
Orthologous groupCOG0139
EC number EC 3.5.4.19, EC 3.6.1.31
KEGG orthology K01496, K11755
KEGG pathways map00340, map01100, map01110, map01230
KEGG modules M00026
Gene Ontology (2) GO:0008150, GO:0040007

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 0.955 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
PRA-CHPF01502.24 1.4e-3433–105 Phosphoribosyl-AMP cyclohydrolase

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

Closest characterised functional partner: hisA (1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 999 1000 ctx neighborhood:881 fusion:889 cooccurence:769 coexpression:968 database:900 textmining:590
Rv1602 hisH imidazole glycerol phosphate synthase subunit HisH 998 998 ctx neighborhood:876 cooccurence:773 coexpression:926 textmining:492
Rv1601 hisB imidazole glycerol-phosphate dehydratase 999 997 ctx neighborhood:876 cooccurence:774 coexpression:887 textmining:759
Rv1605 hisF imidazole glycerol phosphate synthase subunit HisF 999 997 ctx neighborhood:881 cooccurence:774 coexpression:910 textmining:695
Rv1599 hisD histidinol dehydrogenase 999 996 ctx neighborhood:876 cooccurence:774 coexpression:865 textmining:848
Rv2122c hisE phosphoribosyl-ATP pyrophosphatase 992 990 coexpression:857 database:900
Rv1600 hisC1 histidinol-phosphate aminotransferase 996 988 ctx neighborhood:876 cooccurence:668 coexpression:740 textmining:692
Rv1604 impA inositol-monophosphatase ImpA 978 977 ctx neighborhood:881 coexpression:817
Rv2121c hisG ATP phosphoribosyltransferase 983 968 ctx cooccurence:749 coexpression:857 textmining:516
Rv3772 hisC2 histidinol-phosphate aminotransferase 805 785 coexpression:694
Rv2231c cobC aminotransferase 792 770 coexpression:695
Rv3859c gltB glutamate synthase large subunit 736 656 ctx neighborhood:544
Rv1598c hyp hypothetical protein 555 555 ctx neighborhood:553
Rv1613 trpA tryptophan synthase subunit alpha 600 554 coexpression:445
Rv1612 trpB tryptophan synthase subunit beta 576 554 coexpression:445

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: phosphoribosyl-AMP cyclohydrolase
  • MTBC0 PGAP product: phosphoribosyl-AMP cyclohydrolase
  • Pfam (hmmscan --cut_ga): PRA-CH PF01502.24 (E=1e-34)
  • (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_216638.2)
  • Domains: Pfam-A via hmmscan --cut_ga — PRA-CH (PF01502.24)
  • 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 COG0139
  • Curated reference: UniProt P9WMM7 (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 — 70 functional partner(s); context anchor hisA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001712|Rv1606|hisI
MTLDPKIAARLKRNADGLVTAVVQERGSGDVLMVAWMNDEALARTLQTREATYYSRSRAEQWVKGATSGHTQHVHSVRLDCDGDAVLLTVDQVGGACHTGDHSCFDAAVLLEPDD