proB Resolved · high auto-curated
H37Rv Rv2439c · MTBC0 mtbc0_002598 ·
376 aa · 2761365–2762495 (-) ·
RefSeq NP_216955.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glutamate 5-kinase protein |
|---|---|
| MTBC0 PGAP re-annotation | glutamate 5-kinase |
| Revised (this work) | Glutamate 5-kinase. Pfam: AA_kinase (PF00696.34), PUA (PF01472.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHU9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glutamate 5-kinase |
| EC (curated) |
EC 2.7.2.11
|
| Curated function | Catalyzes the transfer of a phosphate group to glutamate to form L-glutamate 5-phosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | proB |
| eggNOG description | Catalyzes the transfer of a phosphate group to glutamate to form L-glutamate 5-phosphate |
| Orthologous group | COG0263 |
| EC number |
EC 2.7.2.11
|
| KEGG orthology |
K00931
|
| KEGG pathways |
map00330, map00332, map01100, map01130, map01230
|
| KEGG modules |
M00015
|
| Gene Ontology (51) |
GO:0003674, GO:0003824, GO:0004349, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520, GO:0006560, GO:0006561 +39 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 | 0.227 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 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 |
|---|---|---|---|---|
AA_kinase | PF00696.34 | 1.2e-38 | 15–239 | Amino acid kinase family |
PUA | PF01472.27 | 6.1e-16 | 281–350 | PUA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: proA (gamma-glutamyl phosphate reductase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2427c proA |
gamma-glutamyl phosphate reductase | 999 | 1000 ctx | fusion:900 cooccurence:774 coexpression:806 database:900 textmining:705 |
Rv2322c rocD1 |
Rv2322c, (MTCY3G12.12), len: 221 aa. Probable rocD1,ornithine aminotransferase, highly similar to N-terminal region of other ornithine amino | 923 | 915 | database:900 |
Rv2440c obg |
GTPase Obg | 988 | 904 ctx | neighborhood:881 textmining:889 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 914 | 902 | database:900 |
Rv0500 proC |
pyrroline-5-carboxylate reductase | 945 | 832 ctx | cooccurence:660 coexpression:422 textmining:688 |
Rv2441c rpmA |
50S ribosomal protein L27 | 974 | 783 ctx | neighborhood:782 textmining:887 |
Rv2442c rplU |
50S ribosomal protein L21 | 828 | 776 ctx | neighborhood:775 |
Rv2444c rne |
ribonuclease E | 562 | 563 ctx | neighborhood:544 |
Rv3709c ask |
aspartokinase | 548 | 420 | |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 425 | 388 | |
Rv2192c trpD |
anthranilate phosphoribosyltransferase | 525 | 379 | |
Rv1294 thrA |
homoserine dehydrogenase | 487 | 331 | |
Rv0884c serC |
phosphoserine aminotransferase | 482 | 325 | |
Rv1654 argB |
acetylglutamate kinase | 729 | 311 | textmining:624 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 418 | 240 |
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: glutamate 5-kinase protein
- MTBC0 PGAP product: glutamate 5-kinase
- Pfam (hmmscan --cut_ga): AA_kinase PF00696.34 (E=1e-38), PUA PF01472.27 (E=6e-16)
- (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_216955.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_kinase (PF00696.34), PUA (PF01472.27)
- 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
COG0263 - Curated reference: UniProt P9WHU9 (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 —
28 functional partner(s); context anchor
proA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002598|Rv2439c|proB MRSPHRDAIRTARGLVVKVGTTALTTPSGMFDAGRLAGLAEAVERRMKAGSDVVIVSSGAIAAGIEPLGLSRRPKDLATKQAAASVGQVALVNSWSAAFARYGRTVGQVLLTAHDISMRVQHTNAQRTLDRLRALHAVAIVNENDTVATNEIRFGDNDRLSALVAHLVGADALVLLSDIDGLYDCDPRKTADATFIPEVSGPADLDGVVAGRSSHLGTGGMASKVSAALLAADAGVPVLLAPAADAATALADASVGTVFAARPARLSARRFWVRYAAEATGALTLDAGAVRAVVRQRRSLLAAGITAVSGRFCGGDVVELRAPDAAMVARGVVAYDASELATMVGRSTSELPGELRRPVVHADDLVAVSAKQAKQV