hisC2 Resolved · high auto-curated

H37Rv Rv3772 · MTBC0 mtbc0_003999 · 353 aa · 4241255–4242316 (+) · RefSeq NP_218289.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)histidinol-phosphate aminotransferase
MTBC0 PGAP re-annotationhistidinol-phosphate transaminase
Revised (this work)Histidinol-phosphate transaminase. Pfam: Aminotran_1_2 (PF00155.28).

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

Curated reference (UniProt)

UniProt P9WML5 SwissProt · reviewed · Evidence at protein level
UniProt nameAromatic amino acid aminotransferase
EC (curated) EC 2.6.1.57
Curated functionAminotransferase that catalyzes the conversion of aromatic amino acids and 2-oxoglutarate into corresponding aromatic oxo acids and L-glutamate. Shows excellent activity with phenylalanine, and lower activity with tyrosine and tryptophan. Has no significant activity with histidinol phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namepat
eggNOG descriptionMay catalyze the transamination reaction in phenylalanine biosynthesis
Orthologous groupCOG0079
EC number EC 2.6.1.9
KEGG orthology K00817
KEGG pathways map00340, map00350, map00360, map00400, map00401, map00960, map01100, map01110, map01130, map01230
KEGG modules M00026

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 0.218 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (206) · clonal

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
Aminotran_1_2PF00155.28 1.1e-5325–338 Aminotransferase class I and II

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

Closest characterised functional partner: hisB (imidazole glycerol-phosphate dehydratase), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1601 hisB imidazole glycerol-phosphate dehydratase 997 997 ctx fusion:860 coexpression:692 database:900
Rv3754 tyrA prephenate dehydrogenase TyrA 969 966 coexpression:654 database:900
Rv1599 hisD histidinol dehydrogenase 950 931 ctx fusion:666 coexpression:692
Rv1600 hisC1 histidinol-phosphate aminotransferase 916 917 database:900
Rv2231c cobC aminotransferase 910 910 database:900
Rv3838c pheA prephenate dehydratase 916 907 database:900
Rv3137 hisN histidinol-phosphatase 908 903 database:900
Rv1908c katG catalase-peroxidase 905 900 database:900
Rv1605 hisF imidazole glycerol phosphate synthase subunit HisF 828 810 coexpression:694
Rv1602 hisH imidazole glycerol phosphate synthase subunit HisH 827 809 coexpression:693
Rv3215 entC isochorismate synthase 812 805 database:800
Rv2949c chorismate pyruvate-lyase 800 800 database:800
Rv1606 hisI phosphoribosyl-AMP cyclohydrolase 805 785 coexpression:694
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 791 769 coexpression:692
Rv2121c hisG ATP phosphoribosyltransferase 785 744 coexpression:697

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-phosphate aminotransferase
  • MTBC0 PGAP product: histidinol-phosphate transaminase
  • Pfam (hmmscan --cut_ga): Aminotran_1_2 PF00155.28 (E=1e-53)
  • (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_218289.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Aminotran_1_2 (PF00155.28)
  • 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 COG0079
  • Curated reference: UniProt P9WML5 (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 — 53 functional partner(s); context anchor hisB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003999|Rv3772|hisC2
MTARLRPELAGLPVYVPGKTVPGAIKLASNETVFGPLPSVRAAIDRATDTVNRYPDNGCVQLKAALARHLGPDFAPEHVAVGCGSVSLCQQLVQVTASVGDEVVFGWRSFELYPPQVRVAGAIPIQVPLTDHTFDLYAMLAAVTDRTRLIFVCNPNNPTSTVVGPDALARFVEAVPAHILIAIDEAYVEYIRDGMRPDSLGLVRAHNNVVVLRTFSKAYGLAGLRIGYAIGHPDVITALDKVYVPFTVSSIGQAAAIASLDAADELLARTDTVVAERARVSAELRAAGFTLPPSQANFVWLPLGSRTQDFVEQAADARIVVRPYGTDGVRVTVAAPEENDAFLRFARRWRSDQ