guaA Resolved · high auto-curated
H37Rv Rv3396c · MTBC0 mtbc0_003609 ·
525 aa · 3837940–3839517 (-) ·
RefSeq NP_217913.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GMP synthase |
|---|---|
| MTBC0 PGAP re-annotation | glutamine-hydrolyzing GMP synthase |
| Revised (this work) | Glutamine-hydrolyzing GMP synthase. Pfam: GATase (PF00117.35), Peptidase_C26 (PF07722.20), NAD_synthase (PF02540.24), GMP_synt_C (PF00958.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMS7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GMP synthase [glutamine-hydrolyzing] |
| EC (curated) |
EC 6.3.5.2
|
| Curated function | Catalyzes the synthesis of GMP from XMP. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | guaA |
| eggNOG description | Catalyzes the synthesis of GMP from XMP |
| Orthologous group | COG0518 |
| EC number |
EC 6.3.5.2
|
| KEGG orthology |
K01951
|
| KEGG pathways |
map00230, map00983, map01100
|
| KEGG modules |
M00050
|
| Gene Ontology (82) |
GO:0003674, GO:0003824, GO:0003921, GO:0003922, GO:0005575, GO:0005618, GO:0005623, GO:0006139, GO:0006163, GO:0006164, GO:0006177, GO:0006725 +70 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 | 0.197 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 5 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 | 7.8e-43 | 18–198 | Glutamine amidotransferase class-I |
Peptidase_C26 | PF07722.20 | 1.8e-07 | 81–181 | Peptidase C26 |
NAD_synthase | PF02540.24 | 1.7e-05 | 215–257 | NAD synthase |
GMP_synt_C | PF00958.28 | 2.0e-39 | 432–524 | GMP synthase C terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: guaB2 (inosine-5'-monophosphate dehydrogenase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 999 | 999 ctx | neighborhood:544 cooccurence:665 coexpression:952 database:900 textmining:942 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 999 | 999 ctx | cooccurence:626 coexpression:952 database:900 textmining:653 |
Rv3410c guaB3 |
oxidoreductase | 998 | 997 | coexpression:952 database:900 textmining:497 |
Rv2584c apt |
adenine phosphoribosyltransferase | 996 | 992 | coexpression:872 database:900 textmining:554 |
Rv1292 argS |
arginine--tRNA ligase | 988 | 980 | coexpression:979 textmining:432 |
Rv0640 rplK |
50S ribosomal protein L11 | 976 | 977 | coexpression:976 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 975 | 963 ctx | cooccurence:409 database:900 |
Rv1699 pyrG |
CTP synthase | 981 | 961 | coexpression:920 textmining:554 |
Rv1389 gmk |
guanylate kinase | 982 | 955 | coexpression:401 database:900 textmining:621 |
Rv0734 mapA |
methionine aminopeptidase | 943 | 941 | coexpression:933 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 973 | 940 | database:900 textmining:587 |
Rv2861c mapB |
methionine aminopeptidase | 942 | 939 | coexpression:931 |
Rv0651 rplJ |
50S ribosomal protein L10 | 933 | 934 | coexpression:934 |
Rv2094c tatA |
Sec-independent protein translocase membrane-bound protein TatA | 935 | 933 | coexpression:921 |
Rv1224 tatB |
Sec-independent protein translocase protein TatB | 935 | 933 | coexpression:921 |
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: GMP synthase
- MTBC0 PGAP product: glutamine-hydrolyzing GMP synthase
- Pfam (hmmscan --cut_ga): GATase PF00117.35 (E=8e-43), Peptidase_C26 PF07722.20 (E=2e-07), NAD_synthase PF02540.24 (E=2e-05), GMP_synt_C PF00958.28 (E=2e-39)
- (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_217913.1)
- Domains: Pfam-A via hmmscan --cut_ga — GATase (PF00117.35), Peptidase_C26 (PF07722.20), NAD_synthase (PF02540.24), GMP_synt_C (PF00958.28)
- 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
COG0518 - Curated reference: UniProt P9WMS7 (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 —
385 functional partner(s); context anchor
guaB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003609|Rv3396c|guaA MVQPADIDVPETPARPVLVVDFGAQYAQLIARRVREARVFSEVIPHTASIEEIRARQPVALVLSGGPASVYADGAPKLDPALLDLGVPVLGICYGFQAMAQALGGIVAHTGTREYGRTELKVLGGKLHSDLPEVQPVWMSHGDAVTAAPDGFDVVASSAGAPVAAFEAFDRRLAGVQYHPEVMHTPHGQQVLSRFLHDFAGLGAQWTPANIANALIEQVRTQIGDGHAICGLSGGVDSAVAAALVQRAIGDRLTCVFVDHGLLRAGERAQVQRDFVAATGANLVTVDAAETFLEALSGVSAPEGKRKIIGRQFIRAFEGAVRDVLDGKTAEFLVQGTLYPDVVESGGGSGTANIKSHHNVGGLPDDLKFTLVEPLRLLFKDEVRAVGRELGLPEEIVARQPFPGPGLGIRIVGEVTAKRLDTLRHADSIVREELTAAGLDNQIWQCPVVLLADVRSVGVQGDGRTYGHPIVLRPVSSEDAMTADWTRVPYEVLERISTRITNEVAEVNRVVLDITSKPPATIEWE