guaB1 Family assigned · medium auto-curated
H37Rv Rv1843c · MTBC0 mtbc0_001956 ·
479 aa · 2110303–2111742 (-) ·
RefSeq NP_216359.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | inosine-5'-monophosphate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | GuaB1 family IMP dehydrogenase-related protein |
| Revised (this work) | GuaB1 family IMP dehydrogenase-related protein. 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 |
P9WKI3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GMP reductase |
| EC (curated) |
EC 1.7.1.7
|
| Curated function | Involved in the purine-salvage pathway. Catalyzes the NADPH-dependent conversion of GMP to IMP. Has no inosine-5'-monophosphate dehydrogenase (IMPDH) activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | guaB1 |
| eggNOG description | IMP dehydrogenase GMP reductase |
| Orthologous group | COG0516 |
| EC number |
EC 1.1.1.205
|
| KEGG orthology |
K00088
|
| KEGG pathways |
map00230, map00983, map01100, map01110
|
| KEGG modules |
M00050
|
| Gene Ontology (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, 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 | 0.515 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 7 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 | 2.8e-98 | 14–474 | IMP dehydrogenase / GMP reductase domain |
CBS | PF00571.34 | 2.4e-05 | 94–142 | 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 | cooccurence:626 coexpression:952 database:900 textmining:653 |
Rv0357c purA |
adenylosuccinate synthetase | 981 | 973 | coexpression:645 database:900 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 957 | 950 | coexpression:422 database:900 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 960 | 928 | database:900 textmining:474 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 934 | 927 | database:900 |
Rv3410c guaB3 |
oxidoreductase | 988 | 910 | database:900 textmining:877 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 934 | 904 | database:900 |
Rv1021 mazG |
nucleoside triphosphate pyrophosphohydrolase | 906 | 901 | database:900 |
Rv1844c gnd1 |
6-phosphogluconate dehydrogenase | 847 | 846 ctx | neighborhood:836 |
Rv1846c blaI |
transcriptional repressor BlaI | 830 | 830 ctx | neighborhood:794 |
Rv1845c blaR |
sensor-transducer protein BlaR | 826 | 819 ctx | neighborhood:802 |
Rv1842c hyp |
hypothetical protein | 815 | 808 ctx | neighborhood:743 |
Rv1841c hyp |
hypothetical protein | 789 | 781 ctx | neighborhood:743 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 774 | 703 | coexpression:694 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta | 730 | 687 | coexpression:646 |
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: GuaB1 family IMP dehydrogenase-related protein
- Pfam (hmmscan --cut_ga): IMPDH PF00478.32 (E=3e-98), CBS PF00571.34 (E=2e-05)
- (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_216359.1)
- 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 P9WKI3 (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 —
121 functional partner(s); context anchor
guaA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001956|Rv1843c|guaB1 MMRFLDGHPPGYDLTYNDVFIVPNRSEVASRFDVDLSTADGSGTTIPVVVANMTAVAGRRMAETVARRGGIVILPQDLPIPAVKQTVAFVKSRDLVLDTPVTLAPDDSVSDAMALIHKRAHGVAVVILEGRPIGLVRESSCLGVDRFTRVRDIAVTDYVTAPAGTEPRKIFDLLEHAPVDVAVLTDADGTLAGVLSRTGAIRAGIYTPATDSAGRLRIGAAVGINGDVGAKARALAEAGVDVLVIDTAHGHQVKTLDAIKAVSALDLGLPLAAGNVVSAEGTRDLLKAGANVVKVGVGPGAMCTTRMMTGVGRPQFSAVLECASAARQLGGHIWADGGIRHPRDVALALAAGASNVMIGSWFAGTYESPGDLMRDRDDQPYKESYGMASKRAVVARTGADNPFDRARKALFEEGISTSRMGLDPDRGGVEDLIDHITSGVRSTCTYVGASNLAELHERAVVGVQSGAGFAEGHPLPAGW