tyzA Resolved · high
H37Rv Rv2336 · MTBC0 mtbc0_002486 ·
322 aa · 2635587–2636555 (+) ·
RefSeq NP_216852.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | TyzA, an N-acyltransferase of the tyz (tyrazolone) gene cluster that initiates the biosynthesis of acyl-oxazolones, a novel class of M. tuberculosis lipids. RefSeq leaves this locus 'hypothetical protein'. Heterologous expression of tyzA (Rv2336), tyzB (Rv2338c) and tyzC (Rv2337c) produces C12:0-tyrazolone, also found in Mtb lipid extracts; TyzA catalyses the N-acylation of L-amino acids with highest specificity for L-Tyr/L-Phe and lauroyl-CoA (kcat/KM = 5.9e3 M-1 s-1) (Grigg 2023). The tyz cluster was previously implicated in oxidative-stress resistance and macrophage survival. Experimentally characterised enzyme. |
Curated reference (UniProt)
| UniProt |
P95232
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.323 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (170) · 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)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 866 | 58 | textmining:864 |
Rv1754c hyp |
hypothetical protein | 657 | 55 | textmining:652 |
Rv0403c mmpS1 |
membrane protein MmpS1 | 655 | 53 | textmining:651 |
Rv2770c PPE44 |
PPE family protein PPE44 | 870 | 47 | textmining:870 |
Rv0963c hyp |
hypothetical protein | 806 | 46 | textmining:805 |
Rv0288 esxH |
ESAT-6-like protein EsxH | 512 | 42 | textmining:512 |
Rv1320c |
adenylate cyclase | 804 | 41 | textmining:804 |
Rv1345 mbtM |
long-chain-fatty-acid--ACP ligase MbtM | 803 | 41 | textmining:803 |
Rv0796 |
Putative transposase for insertion sequence element IS6110; Involved in the transposition of the insertion sequence. | 430 | 41 | textmining:430 |
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
- N-acyltransferase; N-acylation of L-amino acids (L-Tyr/L-Phe) with lauroyl-CoA, kcat/KM 5.9e3 M-1 s-1 (Grigg 2023, PMID 37328106)
- First step of acyl-oxazolone (tyrazolone) lipid biosynthesis; tyz cluster tyzA(Rv2336)-tyzB(Rv2338c)-tyzC(Rv2337c)
- Renamed tyzA
- 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_216852.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt P95232 (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 — 9 functional partner(s)
- 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_002486|Rv2336|tyzA MDVPHEQPALSSSKSNRFTSQRQTTGVGTTTVERLEPRLSPASRHITEAKAFGTECHVSSFTREQDPDRAVRVEQIHGEAYVAAGHVYESALDELGRLDNSNAEFILDKARGSTRETEVIYLHAVPAEPLSGSQGEGGLRIVGISAVGSIDDLSAFKAAKPSMGLAHQRKLYDAIEDLGHGGVKEIAALSVTADAPPTVSYSLIREVLRLYHRTGEKLIITFAMPAYAKMVMNFGRFAMPQVGEPFYAHRNNDPRTSNDLLLVPSIVEPSNFLENISRGVVTADDGPTARRRFATLCYMTDGLDDYFMPLTRQVLSEGIQDI