gmk Resolved · high auto-curated
H37Rv Rv1389 · MTBC0 mtbc0_001490 ·
208 aa · 1573745–1574371 (+) ·
RefSeq NP_215905.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | guanylate kinase |
|---|---|
| MTBC0 PGAP re-annotation | guanylate kinase |
| Revised (this work) | Guanylate kinase. Pfam: Guanylate_kin (PF00625.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKE9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Guanylate kinase |
| EC (curated) |
EC 2.7.4.8
|
| Curated function | Essential for recycling GMP and indirectly, cGMP. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | gmk |
| eggNOG description | Essential for recycling GMP and indirectly, cGMP |
| Orthologous group | COG3709 |
| EC number |
EC 2.7.4.8
|
| KEGG orthology |
K00942
|
| KEGG pathways |
map00230, map01100
|
| KEGG modules |
M00050
|
| Gene Ontology (102) |
GO:0000166, GO:0000287, GO:0001882, GO:0001883, GO:0003674, GO:0003824, GO:0004017, GO:0004385, GO:0005488, GO:0005524, GO:0005575, GO:0005622 +90 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 | 0.092 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 1 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 |
|---|---|---|---|---|
Guanylate_kin | PF00625.28 | 7.1e-40 | 22–200 | Guanylate kinase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpoZ (DNA-directed RNA polymerase subunit omega), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 997 | 970 ctx | neighborhood:796 coexpression:861 textmining:914 |
Rv3396c guaA |
GMP synthase | 982 | 955 | coexpression:401 database:900 textmining:621 |
Rv2584c apt |
adenine phosphoribosyltransferase | 975 | 953 | coexpression:535 database:900 textmining:499 |
Rv1617 pykA |
pyruvate kinase | 937 | 927 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 938 | 920 | database:900 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 963 | 915 | database:900 textmining:593 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 924 | 914 | database:900 |
Rv3051c nrdE |
ribonucleoside-diphosphate reductase subunit alpha | 911 | 901 | database:900 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 910 | 901 | database:900 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 | 907 | 901 | database:900 |
Rv3048c nrdF2 |
ribonucleoside-diphosphate reductase subunit beta NrdF2 | 906 | 901 | database:900 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB | 905 | 900 | database:900 |
Rv1392 metK |
S-adenosylmethionine synthetase | 918 | 899 ctx | neighborhood:699 cooccurence:672 |
Rv1023 eno |
enolase | 902 | 889 | experimental:781 |
Rv1391 dfp |
bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase | 940 | 877 ctx | neighborhood:783 textmining:538 |
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: guanylate kinase
- MTBC0 PGAP product: guanylate kinase
- Pfam (hmmscan --cut_ga): Guanylate_kin PF00625.28 (E=7e-40)
- (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_215905.1)
- Domains: Pfam-A via hmmscan --cut_ga — Guanylate_kin (PF00625.28)
- 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
COG3709 - Curated reference: UniProt P9WKE9 (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 —
175 functional partner(s); context anchor
rpoZ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001490|Rv1389|gmk MSVGEGPDTKPTARGQPAAVGRVVVLSGPSAVGKSTVVRCLRERIPNLHFSVSATTRAPRPGEVDGVDYHFIDPTRFQQLIDQGELLEWAEIHGGLHRSGTLAQPVRAAAATGVPVLIEVDLAGARAIKKTMPEAVTVFLAPPSWQDLQARLIGRGTETADVIQRRLDTARIELAAQGDFDKVVVNRRLESACAELVSLLVGTAPGSP