guaB2 Resolved · high auto-curated
H37Rv Rv3411c · MTBC0 mtbc0_003625 ·
529 aa · 3855369–3856958 (-) ·
RefSeq NP_217928.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | inosine-5'-monophosphate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | IMP dehydrogenase |
| Revised (this work) | IMP dehydrogenase. Pfam: IMPDH (PF00478.32), CBS (PF00571.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKI7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Inosine-5'-monophosphate dehydrogenase |
| EC (curated) |
EC 1.1.1.205
|
| Curated function | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Does not catalyze the reverse reaction, i.e. the conversion of XMP to IMP. Appears to be essential for the optimal growth of M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | guaB |
| eggNOG description | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate- limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth |
| Orthologous group | COG0516 |
| EC number |
EC 1.1.1.205
|
| KEGG orthology |
K00088
|
| KEGG pathways |
map00230, map00983, map01100, map01110
|
| KEGG modules |
M00050
|
| Gene Ontology (122) |
GO:0003674, GO:0003824, GO:0003938, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006139, GO:0006163, GO:0006164 +110 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 | 0.24 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 4 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 |
|---|---|---|---|---|
IMPDH | PF00478.32 | 1.2e-153 | 44–515 | IMP dehydrogenase / GMP reductase domain |
CBS | PF00571.34 | 5.6e-10 | 129–176 | CBS domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: guaA (GMP synthase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3396c guaA |
GMP synthase | 999 | 999 ctx | neighborhood:544 cooccurence:665 coexpression:952 database:900 textmining:942 |
Rv3410c guaB3 |
oxidoreductase | 989 | 982 ctx | neighborhood:789 database:900 textmining:417 |
Rv0357c purA |
adenylosuccinate synthetase | 993 | 974 | coexpression:645 database:900 textmining:753 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 972 | 958 | coexpression:421 database:900 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 960 | 928 | database:900 textmining:474 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 935 | 928 | database:900 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 990 | 910 | database:900 textmining:893 |
Rv1021 mazG |
nucleoside triphosphate pyrophosphohydrolase | 907 | 904 | database:900 |
Rv0808 purF |
amidophosphoribosyltransferase | 940 | 890 | coexpression:833 textmining:478 |
Rv3409c choD |
cholesterol oxidase | 806 | 794 ctx | neighborhood:791 |
Rv3412 hyp |
hypothetical protein | 760 | 760 ctx | neighborhood:756 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 788 | 723 | coexpression:713 |
Rv0777 purB |
adenylosuccinate lyase PurB | 943 | 708 | coexpression:648 textmining:814 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta | 693 | 648 | coexpression:648 |
Rv2861c mapB |
methionine aminopeptidase | 690 | 644 | database:478 |
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: inosine-5'-monophosphate dehydrogenase
- MTBC0 PGAP product: IMP dehydrogenase
- Pfam (hmmscan --cut_ga): IMPDH PF00478.32 (E=1e-153), CBS PF00571.34 (E=6e-10)
- (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_217928.1)
- Domains: Pfam-A via hmmscan --cut_ga — IMPDH (PF00478.32), CBS (PF00571.34)
- 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
COG0516 - Curated reference: UniProt P9WKI7 (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 —
150 functional partner(s); context anchor
guaA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003625|Rv3411c|guaB2 MSRGMSGLEDSSDLVVSPYVRMGGLTTDPVPTGGDDPHKVAMLGLTFDDVLLLPAASDVVPATADTSSQLTKKIRLKVPLVSSAMDTVTESRMAIAMARAGGMGVLHRNLPVAEQAGQVEMVKRSEAGMVTDPVTCRPDNTLAQVDALCARFRISGLPVVDDDGALVGIITNRDMRFEVDQSKQVAEVMTKAPLITAQEGVSASAALGLLRRNKIEKLPVVDGRGRLTGLITVKDFVKTEQHPLATKDSDGRLLVGAAVGVGGDAWVRAMMLVDAGVDVLVVDTAHAHNRLVLDMVGKLKSEVGDRVEVVGGNVATRSAAAALVDAGADAVKVGVGPGSICTTRVVAGVGAPQITAILEAVAACRPAGVPVIADGGLQYSGDIAKALAAGASTAMLGSLLAGTAEAPGELIFVNGKQYKSYRGMGSLGAMRGRGGATSYSKDRYFADDALSEDKLVPEGIEGRVPFRGPLSSVIHQLTGGLRAAMGYTGSPTIEVLQQAQFVRITPAGLKESHPHDVAMTVEAPNYYAR