Rv3378c Resolved · medium auto-curated
H37Rv Rv3378c · MTBC0 mtbc0_003593 ·
296 aa · 3819075–3819965 (-) ·
RefSeq NP_217895.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | diterpene synthase |
|---|---|
| MTBC0 PGAP re-annotation | diterpene synthase |
| Revised (this work) | Diterpene synthase. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJ61
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Tuberculosinyl adenosine transferase |
| EC (curated) |
EC 2.5.1.153
|
| Curated function | Tuberculosinyl transferase that catalyzes the condensation of adenosine and tuberculosinyl diphosphate (TbPP) to generate 1-tuberculosinyladenosine (1-TbAd), which acts as an antiacid that directly protects M.tuberculosis from acid pH and physically remodels M.tuberculosis phagolysosomes. In addition, acts as a phosphatase that catalyzes the diphosphate-removal from TbPP to produce both tuberculosinol (TOH) and isotuberculosinol (iso-TOH). Has broad substrate specificity, and can also use the 3 labdadienyl diphosphates, copalyl diphosphate (CDP), ent-CDP and syn-CDP in vitro. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | transferase activity, transferring alkyl or aryl (other than methyl) groups |
| Orthologous group | 28XHJ |
| EC number |
EC 3.1.7.12, EC 3.1.7.8, EC 3.1.7.9
|
| KEGG orthology |
K15911, K22313
|
| Gene Ontology (42) |
GO:0003674, GO:0003824, GO:0006629, GO:0006720, GO:0006721, GO:0006793, GO:0006796, GO:0008150, GO:0008152, GO:0008299, GO:0008610, GO:0009058 +30 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 | 1.017 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (371) · 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: Rv3377c (type B diterpene cyclase), high confidence from genomic context alone (score 938 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3377c |
type B diterpene cyclase | 991 | 938 ctx | neighborhood:882 database:500 textmining:872 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 934 | 803 ctx | neighborhood:801 textmining:680 |
Rv3380c |
Probable transposase; Rv3380c, (MTV004.38c), len: 328 aa. Probable transposase subunit for IS6110. Identical to many other M. tuberculosis I | 883 | 429 ctx | neighborhood:429 textmining:804 |
Rv3381c |
Rv3381c, (MTV004.39c), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase s | 429 | 429 ctx | neighborhood:429 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 768 | 362 | textmining:652 |
Rv3383c idsB |
polyprenyl synthetase IdsB | 904 | 346 | textmining:860 |
Rv3375 amiD |
amidase | 524 | 67 | textmining:511 |
Rv2435c |
cyclase | 863 | 55 | textmining:861 |
Rv3376 |
phosphatase | 871 | 53 | textmining:870 |
Rv1288 hyp |
hypothetical protein | 633 | 51 | textmining:630 |
Rv3373 echA18 |
enoyl-CoA hydratase | 515 | 51 | textmining:510 |
Rv2550c vapB20 |
antitoxin VapB20 | 514 | 50 | textmining:510 |
Rv2275 |
cyclo(L-tyrosyl-L-tyrosyl) synthase | 652 | 47 | textmining:650 |
Rv0064 |
transmembrane protein | 525 | 47 | textmining:523 |
Rv2547 vapB19 |
antitoxin VapB19 | 405 | 47 | textmining:402 |
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: diterpene synthase
- MTBC0 PGAP product: diterpene synthase
- (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_217895.1)
- 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
28XHJ - Curated reference: UniProt P9WJ61 (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 —
20 functional partner(s); context anchor
Rv3377c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003593|Rv3378c| MNLVSEKEFLDLPLVSVAEIVRCRGPKVSVFPFDGTRRWFHLECNPQYDDYQQAALRQSIRILKMLFEHGIETVISPIFSDDLLDRGDRYIVQALEGMALLANDEEILSFYKEHEVHVLFYGDYKKRLPSTAQGAAVVKSFDDLTISTSSNTEHRLCFGVFGNDAAESVAQFSISWNETHGKPPTRREIIEGYYGEYVDKADMFIGFGRFSTFDFPLLSSGKTSLYFTVAPSYYMTETTLRRILYDHIYLRHFRPKPDYSAMSADQLNVLRNRYRAQPDRVFGVGCVHDGIWFAEG