Rv3698 Family assigned · medium auto-curated
H37Rv Rv3698 · MTBC0 - ·
509 aa · 4140493–4142022 (+) ·
RefSeq NP_218215.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains GCS2 (PF04107.19) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
I6YCS6
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | glutamate--cysteine ligase |
| Orthologous group | COG2170 |
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 | 0.979 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 15 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.48% of strains (691) · clonal |
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 |
|---|---|---|---|---|
GCS2 | PF04107.19 | 9.1e-21 | 64–480 | Glutamate-cysteine ligase family 2(GCS2) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: glpK (glycerol kinase), high confidence from genomic context alone (score 745 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3696c glpK |
glycerol kinase | 745 | 745 ctx | neighborhood:744 |
Rv3699 hyp |
hypothetical protein | 717 | 716 ctx | neighborhood:715 |
Rv3697c vapC48 |
ribonuclease VapC48 | 944 | 589 ctx | neighborhood:589 textmining:870 |
Rv3697A vapB48 |
antitoxin VapB48 | 589 | 589 ctx | neighborhood:589 |
Rv1364c |
sigma factor regulatory protein | 548 | 547 | coexpression:532 |
Rv0857 hyp |
hypothetical protein | 498 | 498 ctx | cooccurence:486 |
Rv2185c TB16.3 hyp |
hypothetical protein | 472 | 472 ctx | cooccurence:472 |
Rv0474 |
HTH-type transcriptional regulator | 464 | 465 ctx | cooccurence:457 |
Rv0502 hyp |
hypothetical protein | 447 | 448 ctx | cooccurence:446 |
Rv1294 thrA |
homoserine dehydrogenase | 403 | 403 | coexpression:402 |
Rv3710 leuA |
2-isopropylmalate synthase | 635 | 55 | textmining:630 |
Rv3316 sdhC |
succinate dehydrogenase cytochrome B-556 subunit | 521 | 54 | textmining:515 |
Rv1979c |
permease | 429 | 51 | textmining:423 |
Rv1989c mbcT hyp |
hypothetical protein | 626 | 47 | textmining:624 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 514 | 47 | textmining:511 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): GCS2 PF04107.19 (E=9e-21)
- (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_218215.1)
- Domains: Pfam-A via hmmscan --cut_ga — GCS2 (PF04107.19)
- 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
COG2170 - Curated reference: UniProt I6YCS6 (TrEMBL, unreviewed; 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 —
15 functional partner(s); context anchor
glpK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3698| MRTISPFLRCRHETCCISNVGEEVTRTTYSREHQREYRRKVRLCLDVFETMLAQTRFEADRPLTGMEIECNLVDADYQPAMSNRYVLDAIADPAYQTELGAYNIEFNVPPRPLPGRTCLELEDEVRASLNDAETKASCSGAHIVMIGILPTLMPEHLTDGWMSASARYAALNESIFKARGEDIPINIAGPEPLSCHAGSIAPESACTSVQLHLQLAPADFPANWNAAQVLAGPQLALGANSPYFFGHQLWSETRIELFTQSTDARPEELKSRGVRPRVWFGERWITSVLDLFQENIRYFPTLLPEVSDEDPLAELSAGRIPHLSELRLHNGTVYRWNRPVYDVVDGRPHLRLENRVLPAGPTVVDMLANHAFYYGALRGLSEADPPLWTQMNFAAAQANFLAAARYGMDAQLDWPGLGEVTTRELVLGTLLPMAHEGLRRWGVDAEVRDRFLGVIGGRAQTGRNGARWQVATVAALQDGGLTRPAALAEMLRRYCEHMHSNEPVHTWDT