TB27.3 Family assigned · medium auto-curated
H37Rv Rv0577 · MTBC0 mtbc0_000607 ·
261 aa · 674717–675502 (+) ·
RefSeq NP_215091.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | VOC family protein |
| Revised (this work) | VOC family protein. Pfam: Glyoxalase (PF00903.32), Glyoxalase_6 (PF18029.8). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIR3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative glyoxylase CFP32 |
| Curated function | May function as a glyoxylase involved in the methylglyoxal detoxification pathway. Induces maturation of dendritic cells in a TLR2-dependent manner, causing increased expression of cell-surface molecules (CD80, CD86, MHC class I and II) and pro-inflammatory cytokines (TNF, IL-6, IL-1 beta and IL-12p70). Acts via both the NF-kappa-B and MAPK signaling pathways. Induces Th1-polarized immune responses. |
UniProt still lists this protein as Putative glyoxylase CFP32; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | glyoxalase bleomycin resistance protein dioxygenase |
| Orthologous group | COG3324 |
| KEGG orthology |
K06996
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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) pseudogene candidate
| pN/pS | 1.895 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 2.23% of strains (3240) · 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 |
|---|---|---|---|---|
Glyoxalase | PF00903.32 | 5.4e-17 | 13–124 | Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily |
Glyoxalase_6 | PF18029.8 | 6.5e-09 | 152–254 | Glyoxalase-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0576 (transcriptional regulator), high confidence from genomic context alone (score 767 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) |
|---|---|---|---|---|
Rv0576 |
transcriptional regulator | 767 | 767 ctx | neighborhood:755 |
Rv0575c |
oxidoreductase | 554 | 544 ctx | neighborhood:539 |
Rv0887c hyp |
hypothetical protein | 653 | 322 | textmining:510 |
Rv0911 hyp |
hypothetical protein | 406 | 246 | |
Rv3369 hyp |
hypothetical protein | 510 | 173 | textmining:433 |
Rv3349c |
transposase | 674 | 156 | textmining:630 |
Rv1191 hyp |
hypothetical protein | 463 | 91 | textmining:434 |
Rv1636 TB15.3 |
iron-regulated universal stress protein | 419 | 55 | textmining:411 |
Rv0831c hyp |
hypothetical protein | 444 | 52 | textmining:438 |
Rv1510 hyp |
hypothetical protein | 810 | 50 | textmining:809 |
Rv3044 fecB |
FeIII-dicitrate-binding periplasmic lipoprotein | 771 | 50 | textmining:769 |
Rv0652 rplL |
50S ribosomal protein L7/L12 | 416 | 50 | textmining:411 |
Rv2298 |
oxidoreductase | 804 | 47 | textmining:803 |
Rv3877 eccD1 |
ESX-1 secretion system protein EccD1 | 514 | 47 | textmining:511 |
Rv3248c sahH |
adenosylhomocysteinase | 438 | 47 | textmining:435 |
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: VOC family protein
- Pfam (hmmscan --cut_ga): Glyoxalase PF00903.32 (E=5e-17), Glyoxalase_6 PF18029.8 (E=7e-09)
- (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_215091.1)
- Domains: Pfam-A via hmmscan --cut_ga — Glyoxalase (PF00903.32), Glyoxalase_6 (PF18029.8)
- 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
COG3324 - Curated reference: UniProt P9WIR3 (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 —
18 functional partner(s); context anchor
Rv0576 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000607|Rv0577|TB27.3 MPKRSEYRQGTPNWVDLQTTDQSAAKKFYTSLFGWGYDDNPVPGGGGVYSMATLNGEAVAAIAPMPPGAPEGMPPIWNTYIAVDDVDAVVDKVVPGGGQVMMPAFDIGDAGRMSFITDPTGAAVGLWQANRHIGATLVNETGTLIWNELLTDKPDLALAFYEAVVGLTHSSMEIAAGQNYRVLKAGDAEVGGCMEPPMPGVPNHWHVYFAVDDADATAAKAAAAGGQVIAEPADIPSVGRFAVLSDPQGAIFSVLKPAPQQ