Rv3304 Resolved · high auto-curated
H37Rv Rv3304 · MTBC0 mtbc0_003512 ·
159 aa · 3713279–3713758 (+) ·
RefSeq NP_217821.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | gamma-glutamylcyclotransferase |
| Revised (this work) | Gamma-glutamylcyclotransferase. Pfam: GGACT (PF06094.18), AIG2_2 (PF13772.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53356
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 |
P Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | AIG2-like family |
| Orthologous group | COG3703 |
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 |
|---|---|---|---|---|
GGACT | PF06094.18 | 2.8e-09 | 5–114 | Gamma-glutamyl cyclotransferase, AIG2-like |
AIG2_2 | PF13772.12 | 2.1e-25 | 59–145 | AIG2-like family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpdA (NAD(P)H quinone reductase LpdA), high confidence from genomic context alone (score 762 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) |
|---|---|---|---|---|
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 951 | 762 ctx | neighborhood:757 textmining:805 |
Rv3302c glpD2 |
glycerol-3-phosphate dehydrogenase | 909 | 753 ctx | neighborhood:751 textmining:650 |
Rv3231c hyp |
hypothetical protein | 639 | 639 ctx | cooccurence:638 |
Rv3916c hyp |
hypothetical protein | 608 | 608 ctx | cooccurence:608 |
Rv3118 sseC1 hyp |
hypothetical protein | 601 | 602 ctx | cooccurence:599 |
Rv0814c sseC2 hyp |
hypothetical protein | 601 | 601 ctx | cooccurence:599 |
Rv1332 |
transcriptional regulator | 596 | 596 ctx | cooccurence:596 |
Rv0051 |
transmembrane protein | 519 | 520 ctx | cooccurence:518 |
Rv1159 pimE |
polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase | 493 | 494 ctx | cooccurence:492 |
Rv2181 |
alpha-(1-2)-phosphatidylinositol mannoside mannosyltransferase | 471 | 471 ctx | cooccurence:468 |
Rv1402 priA |
primosomal protein N' | 430 | 431 ctx | cooccurence:428 |
Rv3604c |
transmembrane protein | 423 | 423 ctx | cooccurence:422 |
Rv3300c hyp |
hypothetical protein | 790 | 419 ctx | neighborhood:417 textmining:653 |
Rv0955 |
integral membrane protein | 408 | 409 ctx | cooccurence:404 |
Rv3301c phoY1 |
phosphate transport system transcriptional regulator PhoY | 622 | 360 | textmining:434 |
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: hypothetical protein
- MTBC0 PGAP product: gamma-glutamylcyclotransferase
- Pfam (hmmscan --cut_ga): GGACT PF06094.18 (E=3e-09), AIG2_2 PF13772.12 (E=2e-25)
- (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_217821.1)
- Domains: Pfam-A via hmmscan --cut_ga — GGACT (PF06094.18), AIG2_2 (PF13772.12)
- 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
COG3703 - Curated reference: UniProt O53356 (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 —
24 functional partner(s); context anchor
lpdA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003512|Rv3304| MPLYAAYGSNMHPEQMLERAPHSPMAGTGWLPGWRLTFGGEDIGWEGALATVVEDPDSKVFVVLYDMTPADEKNLDRWEGSEFGIHQKIRCRVERISSDTTTDPVLAWLYVLDAWEGGLPSARYLGVMADAAEIAGAPSDYVHDLRTRPARNIGPGTIA