Rv2558 Family assigned · low
H37Rv Rv2558 · MTBC0 - ·
236 aa · 2877831–2878541 (+) ·
RefSeq NP_217074.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cofactor-independent ABM (antibiotic-biosynthesis-monooxygenase) of the quinone-monooxygenase family (ActVA-Orf6/SnoaB/YgiN), substrate unknown (weaker candidate). RefSeq leaves it 'hypothetical protein'. Tandem-ABM protein (paralogue Rv2557, 69% identity); only the C-terminal lobe forms a competent pocket, centred on His124 and lined by Phe168/Tyr154 - the signature of a cofactorless ABM site where an aromatic substrate replaces flavin. A heme-oxygenase assignment is excluded structurally (geometry not heme-compatible; IsdG/MhuD catalytic determinants absent) and by the fold-paralogue safeguard (heme degradation in M. tuberculosis is already carried by MhuD/Rv3592). HHpred top hits (>=99.9%) are cofactorless ActVA-Orf6/YgiN-family monooxygenases; the IsdG/MhuD heme-oxygenase subfamily is absent. The C-terminal site residues are near-invariant across ~250,724 genomes. Fold and sub-type are well supported; substrate and activity remain undemonstrated. |
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 |
P9WLA3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2558 |
UniProt still lists this protein as Uncharacterized protein Rv2558; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | cellular response to starvation |
| Orthologous group | COG1359 |
| Gene Ontology (15) |
GO:0006950, GO:0007154, GO:0008150, GO:0009267, GO:0009605, GO:0009987, GO:0009991, GO:0031667, GO:0031668, GO:0031669, GO:0033554, GO:0042594 +3 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 | 0.0 · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 90.4 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
3f44-assembly1_A |
1.00 | 0.70 | 9.9e-10 sig | 3f44-assembly1_A Crystal structure of putative monooxygenase (YP_193413.1) from Lactobacillus acidophilus NCFM at 1.55 A resolution |
3mcs-assembly1_A |
1.00 | 0.65 | 1.7e-09 sig | 3mcs-assembly1_A Crystal structure of Putative monooxygenase (FN1347) from FUSOBACTERIUM NUCLEATUM SUBSP. NUCLEATUM ATCC 25586 at 2.55 A resolution |
5f9p-assembly2_B |
1.00 | 0.63 | 6.9e-09 sig | 5f9p-assembly2_B Crystal structure study of anthrone oxidase-like protein |
2pgc-assembly1_C |
1.00 | 0.68 | 7.8e-08 sig | 2pgc-assembly1_C Crystal structure of a a marine metagenome protein (jcvi_pep_1096685590403) from uncultured marine organism at 2.53 A resolution |
3fez-assembly1_A |
1.00 | 0.65 | 7.4e-06 sig | 3fez-assembly1_A Crystal structure of uncharacterized ferredoxin fold protein related to antibiotic biosynthesis monooxygenases (YP_014836.1) from LISTERIA MONOCYTOGENES 4b F2365 at 2.10 A resolution |
2od4-assembly1_B |
1.00 | 0.82 | 2.5e-04 sig | 2od4-assembly1_B Crystal structure of a dimeric ferredoxin-like protein (jcvi_pep_1096665735785) from uncultured marine organism at 1.70 A resolution |
3fgv-assembly1_B |
1.00 | 0.81 | 9.5e-04 sig | 3fgv-assembly1_B CRYSTAL STRUCTURE OF A PUTATIVE ANTIBIOTIC BIOSYNTHESIS MONOOXYGENASE (SPO2313) FROM SILICIBACTER POMEROYI DSS-3 AT 1.30 A RESOLUTION |
4kia-assembly1_A |
1.00 | 0.68 | 2.1e-04 sig | 4kia-assembly1_A Crystal structure of LmHde, heme-degrading enzyme, from Listeria monocytogenes |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3481c (integral membrane protein), medium confidence from genomic context alone (score 525 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) |
|---|---|---|---|---|
Rv2557 hyp |
hypothetical protein | 936 | 935 ctx | neighborhood:547 coexpression:860 |
Rv2160c |
Rv2160c, (MTCY270.08), len: 113 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator, similar to C-terminal | 773 | 773 | coexpression:736 |
Rv2160A |
Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266 | 657 | 657 | coexpression:588 |
Rv2721c hyp |
hypothetical protein | 591 | 591 ctx | cooccurence:590 |
Rv2302 hyp |
hypothetical protein | 550 | 551 ctx | cooccurence:530 |
Rv3481c |
integral membrane protein | 525 | 525 ctx | cooccurence:525 |
Rv1411c lprG |
lipoprotein LprG | 489 | 489 ctx | cooccurence:486 |
Rv1888c |
Rv1888c, (MTCY180.30), len: 186 aa. Possible transmembrane protein. | 481 | 481 ctx | cooccurence:467 |
Rv0569 hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:445 |
Rv2556c hyp |
hypothetical protein | 469 | 469 ctx | neighborhood:466 |
Rv2015c hyp |
hypothetical protein | 457 | 457 ctx | cooccurence:451 |
Rv1765c hyp |
hypothetical protein | 442 | 442 ctx | cooccurence:436 |
Rv1062 hyp |
hypothetical protein | 410 | 411 ctx | cooccurence:407 |
Rv1365c rsfA |
anti-sigma-F factor antagonist RsfA | 407 | 407 | |
Rv3768 hyp |
hypothetical protein | 405 | 405 ctx | cooccurence:401 |
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
- RefSeq: hypothetical protein; tandem ABM, paralogue Rv2557 (69% id)
- Competent C-terminal pocket: His124 with Phe168/Tyr154 (cofactorless ABM signature)
- HHpred >=99.9%: ActVA-Orf6/YgiN cofactorless monooxygenases; IsdG/MhuD heme-oxygenase subfamily absent
- Heme-oxygenase excluded (structure + fold-paralogue safeguard: MhuD/Rv3592 holds that function)
- C-terminal site residues near-invariant across ~250,724 genomes; substrate undemonstrated
- Curated against the companion dark-enzymes re-annotation (Guyeux 2026)
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_217074.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG1359 - Curated reference: UniProt P9WLA3 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 90.4, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
21 functional partner(s); context anchor
Rv3481c - Primary literature: Guyeux C (2026). Structure-guided functional hypotheses for uncharacterised enzymes of Mycobacterium tuberculosis in preparation. doi:10.5281/zenodo.20571950
Ancestral MTBC0 protein sequence
>H37Rv|Rv2558| MPGSAGWRKVFGGTGGATGALPRHGRGSIVYARSTTIEAQPLSVDIGIAHVRDVVMPALQEIDGCVGVSLLVDRQSGRCIATSAWETLEAMRASVERVAPIRDRAALMFAGSARVEEWDIALLHRDHPSHEGACVRATWLKVVPDQLGRSLEFYRTSVLPELESLDGFCSASLMVDHPACRRAVSCSTFDSMDAMARNRDRASELRSRRVRELGAEVLDVAEFELAIAHLRVPELV