hisN Resolved · high auto-curated

H37Rv Rv3137 · MTBC0 mtbc0_003335 · 260 aa · 3526095–3526877 (+) · RefSeq NP_217653.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)histidinol-phosphatase
MTBC0 PGAP re-annotationhistidinol-phosphatase
Revised (this work)Histidinol-phosphatase. Pfam: Inositol_P (PF00459.31).

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

Curated reference (UniProt)

UniProt P95189 SwissProt · reviewed · Evidence at protein level
UniProt nameHistidinol-phosphatase
EC (curated) EC 3.1.3.15
Curated functionCatalyzes the dephosphorylation of histidinol-phosphate to histidinol, the direct precursor of histidine.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namehisN
eggNOG descriptionInositol monophosphatase
Orthologous groupCOG0483
EC number EC 3.1.3.15, EC 3.1.3.25
KEGG orthology K01092, K05602
KEGG pathways map00340, map00521, map00562, map01100, map01110, map01230, map04070
KEGG modules M00026, M00131
Gene Ontology (70) GO:0000105, GO:0003674, GO:0003824, GO:0004401, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006520 +58 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 0.125 · 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
Inositol_PPF00459.31 2.0e-459–254 Inositol monophosphatase family

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

Closest characterised functional partner: pflA (pyruvate formate lyase activating protein PflA), high confidence from genomic context alone (score 888 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1599 hisD histidinol dehydrogenase 941 921 database:900
Rv1600 hisC1 histidinol-phosphate aminotransferase 920 915 database:900
Rv2231c cobC aminotransferase 908 903 database:900
Rv3772 hisC2 histidinol-phosphate aminotransferase 908 903 database:900
Rv3138 pflA pyruvate formate lyase activating protein PflA 937 888 ctx neighborhood:855 textmining:462
Rv3136A hyp hypothetical protein 778 778 ctx neighborhood:778
Rv3135 PPE50 PPE family protein PPE50 733 733 coexpression:733
Rv3139 fadE24 acyl-CoA dehydrogenase 662 606 ctx neighborhood:602
Rv2841c nusA transcription termination/antitermination protein NusA 565 564 experimental:484
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 640 547 ctx neighborhood:543
Rv1407 fmu 16S rRNA m5C967 methyltransferase 634 508 experimental:405
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 503 504 experimental:484
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 502 497 experimental:484
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 491 492 experimental:484
Rv0639 nusG transcription termination/antitermination protein NusG 527 476 experimental:449

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: histidinol-phosphatase
  • MTBC0 PGAP product: histidinol-phosphatase
  • Pfam (hmmscan --cut_ga): Inositol_P PF00459.31 (E=2e-45)
  • (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_217653.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Inositol_P (PF00459.31)
  • 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 COG0483
  • Curated reference: UniProt P95189 (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 — 39 functional partner(s); context anchor pflA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003335|Rv3137|hisN
MSHDDLMLALALADRADELTRVRFGALDLRIDTKPDLTPVTDADRAVESDVRQTLGRDRPGDGVLGEEFGGSTTFTGRQWIVDPIDGTKNFVRGVPVWASLIALLEDGVPSVGVVSAPALQRRWWAARGRGAFASVDGARPHRLSVSSVAELHSASLSFSSLSGWARLGLRERFIGLTDTVWRVRAYGDFLSYCLVAEGAVDIAAEPQVSVWDLAALDIVVREAGGRLTSLDGVAGPHGGSAVATNGLLHDEVLTRLNAG