hisG Resolved · high auto-curated
H37Rv Rv2121c · MTBC0 mtbc0_002253 ·
284 aa · 2407069–2407923 (-) ·
RefSeq NP_216637.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP phosphoribosyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | ATP phosphoribosyltransferase |
| Revised (this work) | ATP phosphoribosyltransferase. Pfam: HisG (PF01634.24), HisG_C (PF08029.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMN1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP phosphoribosyltransferase |
| EC (curated) |
EC 2.4.2.17
|
| Curated function | Catalyzes the condensation of ATP and 5-phosphoribose 1-diphosphate to form N'-(5'-phosphoribosyl)-ATP (PR-ATP). Has a crucial role in the pathway because the rate of histidine biosynthesis seems to be controlled primarily by regulation of HisG enzymatic activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | hisG |
| eggNOG description | ATP phosphoribosyltransferase |
| Orthologous group | COG0040 |
| EC number |
EC 2.4.2.17
|
| KEGG orthology |
K00765, K02502
|
| KEGG pathways |
map00340, map01100, map01110, map01230
|
| KEGG modules |
M00026
|
| Gene Ontology (67) |
GO:0000105, GO:0000166, GO:0000287, GO:0003674, GO:0003824, GO:0003879, GO:0005488, GO:0005524, GO:0005575, GO:0005623, GO:0005886, GO:0006082 +55 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 | 0.176 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HisG | PF01634.24 | 6.3e-42 | 49–204 | ATP phosphoribosyltransferase |
HisG_C | PF08029.17 | 1.8e-25 | 210–280 | HisG, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hisE (phosphoribosyl-ATP pyrophosphatase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2122c hisE |
phosphoribosyl-ATP pyrophosphatase | 999 | 999 ctx | neighborhood:882 cooccurence:713 coexpression:859 database:900 textmining:937 |
Rv1599 hisD |
histidinol dehydrogenase | 996 | 970 ctx | cooccurence:768 coexpression:857 textmining:899 |
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 994 | 969 ctx | cooccurence:764 coexpression:857 textmining:843 |
Rv1602 hisH |
imidazole glycerol phosphate synthase subunit HisH | 987 | 969 ctx | cooccurence:762 coexpression:857 textmining:602 |
Rv1605 hisF |
imidazole glycerol phosphate synthase subunit HisF | 989 | 968 ctx | cooccurence:748 coexpression:857 textmining:701 |
Rv1606 hisI |
phosphoribosyl-AMP cyclohydrolase | 983 | 968 ctx | cooccurence:749 coexpression:857 textmining:516 |
Rv1603 hisA |
1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase | 996 | 961 ctx | cooccurence:705 coexpression:857 textmining:911 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 965 | 932 ctx | cooccurence:756 coexpression:694 textmining:513 |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 863 | 827 | database:800 |
Rv2580c hisS |
histidine--tRNA ligase | 864 | 822 | experimental:790 |
Rv2231c cobC |
aminotransferase | 803 | 782 | coexpression:696 |
Rv2120c |
integral membrane protein | 768 | 768 ctx | neighborhood:765 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 785 | 744 | coexpression:697 |
Rv1516c |
sugar transferase | 706 | 706 | coexpression:703 |
Rv2124c metH |
methionine synthase | 598 | 554 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
- Legacy H37Rv annotation: ATP phosphoribosyltransferase
- MTBC0 PGAP product: ATP phosphoribosyltransferase
- Pfam (hmmscan --cut_ga): HisG PF01634.24 (E=6e-42), HisG_C PF08029.17 (E=2e-25)
- (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_216637.1)
- Domains: Pfam-A via hmmscan --cut_ga — HisG (PF01634.24), HisG_C (PF08029.17)
- 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
COG0040 - Curated reference: UniProt P9WMN1 (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 —
66 functional partner(s); context anchor
hisE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002253|Rv2121c|hisG MLRVAVPNKGALSEPATEILAEAGYRRRTDSKDLTVIDPVNNVEFFFLRPKDIAIYVGSGELDFGITGRDLVCDSGAQVRERLALGFGSSSFRYAAPAGRNWTTADLAGMRIATAYPNLVRKDLATKGIEATVIRLDGAVEISVQLGVADAIADVVGSGRTLSQHDLVAFGEPLCDSEAVLIERAGTDGQDQTEARDQLVARVQGVVFGQQYLMLDYDCPRSALKKATAITPGLESPTIAPLADPDWVAIRALVPRRDVNGIMDELAAIGAKAILASDIRFCRF