tyzC Resolved · high
H37Rv Rv2337c · MTBC0 mtbc0_002487 ·
372 aa · 2636619–2637737 (-) ·
RefSeq NP_216853.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | TyzC, a flavin-dependent oxidase (FDO) of the nitroreductase (NTR) superfamily acting in acyl-oxazolone biosynthesis. RefSeq leaves this locus 'hypothetical protein'. In the tyz cluster, TyzC catalyses the O2-dependent desaturation of the N-acyl-L-Tyr produced by TyzA, while TyzB (a ThiF homolog) catalyses its ATP-dependent cyclisation to the acyl-oxazolone; the substrate preferences of TyzB/TyzC set the identity of the final lipid (Grigg 2023). This work expands the NTR superfamily to a set of broadly distributed FDOs (five in Mtb) that desaturate lipid species. Experimentally characterised enzyme. |
Curated reference (UniProt)
| UniProt |
P95233
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nitroreductase domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | moeY |
| eggNOG description | coenzyme F420-1:gamma-L-glutamate ligase activity |
| Orthologous group | COG0778 |
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 | 0.707 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (241) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moeW (molybdopterin biosynthesis protein MoeW), high confidence from genomic context alone (score 813 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) |
|---|---|---|---|---|
Rv3323c moaX |
MoaD-MoaE fusion protein MoaX | 838 | 814 | coexpression:445 experimental:473 |
Rv2338c moeW |
molybdopterin biosynthesis protein MoeW | 813 | 813 ctx | neighborhood:505 cooccurence:443 |
Rv1004c |
membrane protein | 786 | 777 ctx | cooccurence:766 |
Rv2209 |
integral membrane protein | 769 | 769 ctx | cooccurence:764 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 769 | 769 ctx | cooccurence:769 |
Rv0355c PPE8 |
PPE family protein PPE8 | 768 | 768 ctx | cooccurence:767 |
Rv3347c PPE55 |
PPE family protein PPE55 | 768 | 768 ctx | cooccurence:767 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 767 | 767 ctx | cooccurence:767 |
Rv3350c PPE56 |
PPE family protein PPE56 | 766 | 767 ctx | cooccurence:766 |
Rv0341 iniB |
isoniazid inducible protein IniB | 762 | 763 ctx | cooccurence:762 |
Rv0304c PPE5 |
PPE family protein PPE5 | 762 | 762 ctx | cooccurence:761 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 761 | 761 ctx | cooccurence:761 |
Rv1917c PPE34 |
PPE family protein PPE34 | 761 | 761 ctx | cooccurence:760 |
Rv3343c PPE54 |
PPE family protein PPE54 | 760 | 760 ctx | cooccurence:760 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 759 | 759 ctx | cooccurence:751 |
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
- Flavin-dependent oxidase (nitroreductase superfamily); O2-dependent desaturation of N-acyl-L-Tyr (Grigg 2023, PMID 37328106)
- tyz cluster tyzA(Rv2336)-tyzB(Rv2338c)-tyzC(Rv2337c); acyl-oxazolone (tyrazolone) lipid biosynthesis
- Renamed tyzC
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216853.1)
- 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
COG0778 - Curated reference: UniProt P95233 (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 —
157 functional partner(s); context anchor
moeW - Primary literature: Grigg JC, Copp JN, Krekhno JMC, Liu J, Ibrahimova A, Eltis LD (2023). Deciphering the biosynthesis of a novel lipid in Mycobacterium tuberculosis expands the known roles of the nitroreductase superfamily J Biol Chem 299(7):104924. doi:10.1016/j.jbc.2023.104924 PMID:37328106
Ancestral MTBC0 protein sequence
>mtbc0_002487|Rv2337c|tyzC MRAGRWGPGMTGLDPAEFLSLVEAAALAPSADNRREVQLEHAGRRVRLWGDQTWRSAPEHRRIMSLVAIGAAVENVKLRAGRLGFETKVCWFPDSGNPGLVAEIDVDRLPQTRVDPIEVAIERRRTNRRVRFRGPPLSQGELGALSAEATGIDGIQLHWFDSPETRKQILRLVRLAETERFRSRELHEELFSAVRFDIGWTASSDDGLPPGSLEVEAWMRPMFRGLRHWRVLRLLRTVGMHHALGLRAAYLPCRLAPHVGALTTSLDLASGALTAGAVFERIWLRTTLLGAELQPFAASAVLSLPACEWVAPHVRAALVGGWNLLAPGHWPMMVFRIGHARAPSVRTMRQSVEAYCYAPAERSGSDSESRFA