hisA Resolved · high auto-curated
H37Rv Rv1603 · MTBC0 mtbc0_001709 ·
245 aa · 1815258–1815995 (+) ·
RefSeq NP_216119.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase/phosphoribosylanthranilate isomerase PriA |
| Revised (this work) | Bifunctional 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase/phosphoribosylanthranilate isomerase PriA. Pfam: His_biosynth (PF00977.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMM5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phosphoribosyl isomerase A |
| EC (curated) |
EC 5.3.1.16, EC 5.3.1.24
|
| Curated function | Involved in both the histidine and tryptophan biosynthetic pathways. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | hisA |
| eggNOG description | Involved in both the histidine and tryptophan biosynthetic pathways |
| Orthologous group | COG0106 |
| EC number |
EC 5.3.1.16, EC 5.3.1.24
|
| KEGG orthology |
K01814, K01817
|
| KEGG pathways |
map00340, map00400, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00023, M00026
|
| Gene Ontology (60) |
GO:0000105, GO:0000162, GO:0003674, GO:0003824, GO:0003949, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006520, GO:0006547 +48 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 0 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 |
|---|---|---|---|---|
His_biosynth | PF00977.28 | 5.1e-63 | 6–234 | Histidine biosynthesis protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hisF (imidazole glycerol phosphate synthase subunit HisF), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1605 hisF |
imidazole glycerol phosphate synthase subunit HisF | 999 | 1000 ctx | neighborhood:881 fusion:704 coexpression:968 database:900 textmining:600 |
Rv1602 hisH |
imidazole glycerol phosphate synthase subunit HisH | 999 | 1000 ctx | neighborhood:876 cooccurence:765 coexpression:970 database:900 textmining:632 |
Rv1606 hisI |
phosphoribosyl-AMP cyclohydrolase | 999 | 1000 ctx | neighborhood:881 fusion:889 cooccurence:769 coexpression:968 database:900 textmining:590 |
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 999 | 999 ctx | neighborhood:876 cooccurence:770 coexpression:967 textmining:822 |
Rv1599 hisD |
histidinol dehydrogenase | 999 | 997 ctx | neighborhood:876 cooccurence:771 coexpression:918 textmining:882 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 998 | 997 ctx | neighborhood:876 cooccurence:680 coexpression:920 textmining:567 |
Rv1604 impA |
inositol-monophosphatase ImpA | 997 | 983 ctx | neighborhood:882 coexpression:860 textmining:879 |
Rv2121c hisG |
ATP phosphoribosyltransferase | 996 | 961 ctx | cooccurence:705 coexpression:857 textmining:911 |
Rv1611 trpC |
indole-3-glycerol phosphate synthase | 979 | 928 | database:900 textmining:725 |
Rv2192c trpD |
anthranilate phosphoribosyltransferase | 961 | 909 | database:900 textmining:599 |
Rv2122c hisE |
phosphoribosyl-ATP pyrophosphatase | 963 | 886 | coexpression:857 textmining:693 |
Rv3396c guaA |
GMP synthase | 842 | 777 | coexpression:651 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 791 | 769 | coexpression:692 |
Rv2231c cobC |
aminotransferase | 778 | 754 | coexpression:693 |
Rv2202c adoK |
adenosine kinase | 713 | 702 | coexpression:692 |
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: 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase
- MTBC0 PGAP product: bifunctional 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase/phosphoribosylanthranilate isomerase PriA
- Pfam (hmmscan --cut_ga): His_biosynth PF00977.28 (E=5e-63)
- (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_216119.1)
- Domains: Pfam-A via hmmscan --cut_ga — His_biosynth (PF00977.28)
- 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
COG0106 - Curated reference: UniProt P9WMM5 (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 —
58 functional partner(s); context anchor
hisF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001709|Rv1603|hisA MMPLILLPAVDVVEGRAVRLVQGKAGSQTEYGSAVDAALGWQRDGAEWIHLVDLDAAFGRGSNHELLAEVVGKLDVQVELSGGIRDDESLAAALATGCARVNVGTAALENPQWCARVIGEHGDQVAVGLDVQIIDGEHRLRGRGWETDGGDLWDVLERLDSEGCSRFVVTDITKDGTLGGPNLDLLAGVADRTDAPVIASGGVSSLDDLRAIATLTHRGVEGAIVGKALYARRFTLPQALAAVRD