tyrA Resolved · high auto-curated
H37Rv Rv3754 · MTBC0 - ·
301 aa · 4200421–4201326 (+) ·
RefSeq NP_218271.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | prephenate dehydrogenase TyrA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Prephenate dehydrogenase TyrA. Pfam: PDH_N (PF02153.24), PDH_C (PF20463.4). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
O69721
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Prephenate dehydrogenase |
| EC (curated) |
EC 1.3.1.12
|
| Curated function | Catalyzes the NAD(+)-dependent conversion of prephenate to p-hydroxyphenylpyruvate, with the elimination of carbon dioxide. Is a key regulatory enzyme in tyrosine biosynthesis. Displays no chorismate mutase (CM) activity, in contrast to TyrA from E.coli and some other bacteria, that are bifunctional and possess a CM domain. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | tyrA |
| eggNOG description | prephenate dehydrogenase |
| Orthologous group | COG0287 |
| EC number |
EC 1.3.1.12
|
| KEGG orthology |
K00210, K04517
|
| KEGG pathways |
map00400, map00401, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00025
|
| Gene Ontology (51) |
GO:0000166, GO:0003674, GO:0003824, GO:0005488, GO:0006082, GO:0006520, GO:0006570, GO:0006571, GO:0006725, GO:0006807, GO:0008150, GO:0008152 +39 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 | 0.606 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
PDH_N | PF02153.24 | 1.3e-18 | 9–152 | Prephenate dehydrogenase, nucleotide-binding domain |
PDH_C | PF20463.4 | 1.7e-14 | 156–240 | Prephenate dehydrogenase, dimerization domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tadA (cytidine/deoxycytidylate deaminase), high confidence from genomic context alone (score 753 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 969 | 966 | coexpression:654 database:900 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 968 | 965 | coexpression:648 database:900 |
Rv2231c cobC |
aminotransferase | 968 | 965 | coexpression:649 database:900 |
Rv0948c |
chorismate mutase | 962 | 947 | database:900 |
Rv3838c pheA |
prephenate dehydratase | 992 | 946 | database:900 textmining:874 |
Rv1885c |
chorismate mutase | 954 | 937 | database:900 |
Rv3242c hyp |
hypothetical protein | 833 | 821 | coexpression:821 |
Rv2540c aroF |
chorismate synthase | 944 | 809 | coexpression:709 textmining:719 |
Rv2584c apt |
adenine phosphoribosyltransferase | 816 | 809 | coexpression:798 |
Rv2894c xerC |
tyrosine recombinase XerC | 774 | 774 | coexpression:766 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 770 | 770 | coexpression:770 |
Rv3753c hyp |
hypothetical protein | 759 | 759 ctx | neighborhood:758 |
Rv3752c tadA |
cytidine/deoxycytidylate deaminase | 764 | 753 ctx | neighborhood:750 |
Rv2538c aroB |
3-dehydroquinate synthase | 884 | 712 | coexpression:499 textmining:614 |
Rv3227 aroA |
3-phosphoshikimate 1-carboxyvinyltransferase | 763 | 691 | coexpression:648 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): prephenate dehydrogenase TyrA
- Pfam (hmmscan --cut_ga): PDH_N PF02153.24 (E=1e-18), PDH_C PF20463.4 (E=2e-14)
- (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_218271.3)
- Domains: Pfam-A via hmmscan --cut_ga — PDH_N (PF02153.24), PDH_C (PF20463.4)
- 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
COG0287 - Curated reference: UniProt O69721 (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 —
53 functional partner(s); context anchor
tadA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3754|tyrA MRAAAAAGREVFGYNRSVEGAHGARSDGFDAITDLNQTLTRAAATEALIVLAVPMPALPGMLAHIRKSAPGCPLTDVTSVKCAVLDEVTAAGLQARYVGGHPMTGTAHSGWTAGHGGLFNRAPWVVSVDDHVDPTVWSMVMTLALDCGAMVVPAKSDEHDAAAAAVSHLPHLLAEALAVTAAEVPLAFALAAGSFRDATRVAATAPDLVRAMCEANTGQLAPAADRIIDLLSRARDSLQSHGSIADLADAGHAARTRYDSFPRSDIVTVVIGADKWREQLAAAGRAGGVITSALPSLDSPQ