purH Resolved · high auto-curated
H37Rv Rv0957 · MTBC0 mtbc0_001021 ·
523 aa · 1075420–1076991 (+) ·
RefSeq NP_215472.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase |
| Revised (this work) | Bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase. Pfam: MGS (PF02142.28), AICARFT_IMPCHas (PF01808.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHM7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional purine biosynthesis protein PurH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase |
| EC (curated) |
EC 2.1.2.3, EC 3.5.4.10
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | purH |
| eggNOG description | bifunctional purine biosynthesis protein PurH |
| Orthologous group | COG0138 |
| EC number |
EC 2.1.2.3, EC 3.5.4.10
|
| KEGG orthology |
K00602
|
| KEGG pathways |
map00230, map00670, map01100, map01110, map01130, map01523
|
| KEGG modules |
M00048
|
| Gene Ontology (8) |
GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, 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 | 0.063 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 2 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 |
|---|---|---|---|---|
MGS | PF02142.28 | 1.2e-22 | 22–135 | MGS-like domain |
AICARFT_IMPCHas | PF01808.25 | 5.0e-110 | 141–457 | AICARFT/IMPCHase bienzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: purN (phosphoribosylglycinamide formyltransferase PurN), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 999 | 1000 ctx | neighborhood:882 fusion:899 cooccurence:631 coexpression:860 database:900 textmining:956 |
Rv0777 purB |
adenylosuccinate lyase PurB | 998 | 989 | coexpression:850 database:900 textmining:846 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 983 | 976 | coexpression:727 database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 983 | 976 | coexpression:729 database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 979 | 973 | coexpression:742 database:900 |
Rv0357c purA |
adenylosuccinate synthetase | 988 | 972 | coexpression:671 database:900 textmining:618 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 994 | 969 | coexpression:648 database:900 textmining:845 |
Rv0772 purD |
phosphoribosylamine--glycine ligase | 984 | 969 ctx | cooccurence:732 coexpression:858 textmining:510 |
Rv0808 purF |
amidophosphoribosyltransferase | 978 | 969 ctx | cooccurence:697 coexpression:857 |
Rv0809 purM |
phosphoribosylformylglycinamidine cyclo-ligase PurM | 976 | 962 ctx | cooccurence:705 coexpression:858 textmining:413 |
Rv2584c apt |
adenine phosphoribosyltransferase | 968 | 959 | coexpression:426 database:900 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 972 | 958 | coexpression:421 database:900 |
Rv3275c purE |
5-(carboxyamino)imidazole ribonucleotide mutase | 966 | 955 ctx | cooccurence:679 coexpression:856 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 957 | 950 | coexpression:422 database:900 |
Rv3410c guaB3 |
oxidoreductase | 947 | 942 | coexpression:422 database:900 |
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: bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase
- MTBC0 PGAP product: bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase
- Pfam (hmmscan --cut_ga): MGS PF02142.28 (E=1e-22), AICARFT_IMPCHas PF01808.25 (E=5e-110)
- (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_215472.1)
- Domains: Pfam-A via hmmscan --cut_ga — MGS (PF02142.28), AICARFT_IMPCHas (PF01808.25)
- 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
COG0138 - Curated reference: UniProt P9WHM7 (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 —
96 functional partner(s); context anchor
purN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001021|Rv0957|purH MSTDDGRRPIRRALISVYDKTGLVDLAQGLSAAGVEIISTGSTAKTIADTGIPVTPVEQLTGFPEVLDGRVKTLHPRVHAGLLADLRKSEHAAALEQLGIEAFELVVVNLYPFSQTVESGASVDDCVEQIDIGGPAMVRAAAKNHPSAAVVTDPLGYHGVLAALRAGGFTLAERKRLASLAFQHIAEYDIAVASWMQQTLAPEHPVAAFPQWFGRSWRRVAMLRYGENPHQQAALYGDPTAWPGLAQAEQLHGKDMSYNNFTDADAAWRAAFDHEQTCVAIIKHANPCGIAISSVSVADAHRKAHECDPLSAYGGVIAANTEVSVEMAEYVSTIFTEVIVAPGYAPGALDVLARKKNIRVLVAAEPLAGGSELRPISGGLLIQQSDQLDAHGDNPANWTLATGSPADPATLTDLVFAWRACRAVKSNAIVIAADGATVGVGMGQVNRVDAARLAVERGGERVRGAVAASDAFFPFPDGLETLAAAGVTAVVHPGGSVRDEEVTEAAAKAGVTLYLTGARHFAH