hisH Family assigned · medium auto-curated
H37Rv Rv1602 · MTBC0 mtbc0_001708 ·
206 aa · 1814628–1815248 (+) ·
RefSeq NP_216118.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | imidazole glycerol phosphate synthase subunit HisH |
|---|---|
| MTBC0 PGAP re-annotation | imidazole glycerol phosphate synthase subunit HisH |
| Revised (this work) | Imidazole glycerol phosphate synthase subunit HisH. Pfam: GATase (PF00117.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMM1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Imidazole glycerol phosphate synthase subunit HisH |
| EC (curated) |
EC 3.5.1.2, EC 4.3.2.10
|
| Curated function | IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisH subunit catalyzes the hydrolysis of glutamine to glutamate and ammonia as part of the synthesis of IGP and AICAR. The resulting ammonia molecule is channeled to the active site of HisF (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | hisH |
| eggNOG description | IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisH subunit provides the glutamine amidotransferase activity that produces the ammonia necessary to HisF for the synthesis of IGP and AICAR |
| Orthologous group | COG0118 |
| KEGG orthology |
K02501
|
| KEGG pathways |
map00340, map01100, map01110, map01230
|
| KEGG modules |
M00026
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0030312, GO:0040007, GO:0044464, GO:0071944
|
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 | 1.068 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
GATase | PF00117.35 | 1.0e-18 | 7–201 | Glutamine amidotransferase class-I |
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).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1603 hisA |
1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase | 999 | 1000 ctx | neighborhood:876 cooccurence:765 coexpression:970 database:900 textmining:632 |
Rv1605 hisF |
imidazole glycerol phosphate synthase subunit HisF | 999 | 1000 ctx | neighborhood:876 fusion:900 cooccurence:774 coexpression:915 experimental:926 database:900 textmining:664 |
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:958 database:900 textmining:617 |
Rv1599 hisD |
histidinol dehydrogenase | 999 | 998 ctx | neighborhood:881 cooccurence:774 coexpression:946 textmining:619 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 998 | 998 ctx | neighborhood:881 cooccurence:738 coexpression:931 textmining:582 |
Rv1606 hisI |
phosphoribosyl-AMP cyclohydrolase | 998 | 998 ctx | neighborhood:876 cooccurence:773 coexpression:926 textmining:492 |
Rv1604 impA |
inositol-monophosphatase ImpA | 975 | 974 ctx | neighborhood:876 coexpression:801 |
Rv2121c hisG |
ATP phosphoribosyltransferase | 987 | 969 ctx | cooccurence:762 coexpression:857 textmining:602 |
Rv2122c hisE |
phosphoribosyl-ATP pyrophosphatase | 943 | 889 | coexpression:857 textmining:517 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 839 | 816 | database:800 |
Rv0777 purB |
adenylosuccinate lyase PurB | 819 | 813 | database:800 |
Rv2584c apt |
adenine phosphoribosyltransferase | 811 | 812 | database:800 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 827 | 809 | coexpression:693 |
Rv2231c cobC |
aminotransferase | 813 | 793 | coexpression:694 |
Rv0114 gmhB |
D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase | 742 | 703 | coexpression:679 |
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: imidazole glycerol phosphate synthase subunit HisH
- MTBC0 PGAP product: imidazole glycerol phosphate synthase subunit HisH
- Pfam (hmmscan --cut_ga): GATase PF00117.35 (E=1e-18)
- (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_216118.1)
- Domains: Pfam-A via hmmscan --cut_ga — GATase (PF00117.35)
- 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
COG0118 - Curated reference: UniProt P9WMM1 (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 —
34 functional partner(s); context anchor
hisA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001708|Rv1602|hisH MTAKSVVVLDYGSGNLRSAQRALQRVGAEVEVTADTDAAMTADGLVVPGVGAFAACMAGLRKISGERIIAERVAAGRPVLGVCVGMQILFACGVEFGVQTPGCGHWPGAVIRLEAPVIPHMGWNVVDSAAGSALFKGLDVDARFYFVHSYAAQRWEGSPDALLTWATYRAPFLAAVEDGALAATQFHPEKSGDAGAAVLSNWVDGL