Rv3377c Resolved · high auto-curated
H37Rv Rv3377c · MTBC0 mtbc0_003592 ·
501 aa · 3817565–3819070 (-) ·
RefSeq NP_217894.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | type B diterpene cyclase |
|---|---|
| MTBC0 PGAP re-annotation | type B diterpene cyclase |
| Revised (this work) | Type B diterpene cyclase. Pfam: SQHop_cyclase_C (PF13243.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50406
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Type B diterpene cyclase |
| EC (curated) |
EC 5.5.1.16
|
| Curated function | Catalyzes the formation of tuberculosinyl diphosphate from geranylgeranyl diphosphate (GGPP). It could also react with (14R/S)-14,15-oxidoGGPP to generate 3alpha- and 3beta-hydroxytuberculosinyl diphosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| eggNOG description | Squalene--hopene cyclase |
| Orthologous group | COG1657 |
| EC number |
EC 5.5.1.16
|
| KEGG orthology |
K17811
|
| Gene Ontology (61) |
GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0006629, GO:0006644, GO:0006720, GO:0006721, GO:0006793, GO:0006796, GO:0006950, GO:0007154 +49 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) pseudogene candidate
| pN/pS | 1.165 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 15 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 10.08% of strains (14632) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
SQHop_cyclase_C | PF13243.13 | 9.5e-08 | 338–421 | Squalene-hopene cyclase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3378c (diterpene synthase), high confidence from genomic context alone (score 938 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3378c |
diterpene synthase | 991 | 938 ctx | neighborhood:882 database:500 textmining:872 |
Rv1814 erg3 |
membrane-bound C-5 sterol desaturase | 879 | 842 | experimental:785 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 937 | 801 ctx | neighborhood:801 textmining:697 |
Rv2293c hyp |
hypothetical protein | 737 | 723 ctx | cooccurence:712 |
Rv3383c idsB |
polyprenyl synthetase IdsB | 925 | 567 | textmining:836 |
Rv1004c |
membrane protein | 561 | 561 ctx | cooccurence:561 |
Rv3347c PPE55 |
PPE family protein PPE55 | 551 | 551 ctx | cooccurence:551 |
Rv3468c |
dTDP-glucose 4,6-dehydratase | 572 | 548 | |
Rv0355c PPE8 |
PPE family protein PPE8 | 548 | 548 ctx | cooccurence:548 |
Rv0304c PPE5 |
PPE family protein PPE5 | 542 | 542 ctx | cooccurence:542 |
Rv1753c PPE24 |
PPE family protein PPE24 | 539 | 539 ctx | cooccurence:539 |
Rv3350c PPE56 |
PPE family protein PPE56 | 538 | 538 ctx | cooccurence:538 |
Rv1745c idi |
isopentenyl-diphosphate delta-isomerase | 604 | 532 | coexpression:440 |
Rv1917c PPE34 |
PPE family protein PPE34 | 532 | 532 ctx | cooccurence:532 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 530 | 531 ctx | cooccurence:530 |
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: type B diterpene cyclase
- MTBC0 PGAP product: type B diterpene cyclase
- Pfam (hmmscan --cut_ga): SQHop_cyclase_C PF13243.13 (E=1e-07)
- (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_217894.1)
- Domains: Pfam-A via hmmscan --cut_ga — SQHop_cyclase_C (PF13243.13)
- 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
COG1657 - Curated reference: UniProt O50406 (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 —
77 functional partner(s); context anchor
Rv3378c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003592|Rv3377c| METFRTLLAKAALGNGISSTAYDTAWVAKLGQLDDELSDLALNWLCERQLPDGSWGAEFPFCYEDRLLSTLAAMISLTSNKHRRRRAAQVEKGLLALKNLTSGAFEGPQLDIKDATVGFELIAPTLMAEAARLGLAICHEESILGELVGVREQKLRKLGGSKINKHITAAFSVELAGQDGVGMLDVDNLQETNGSVKYSPSASAYFALHVKPGDKRALAYISSIIQAGDGGAPAFYQAEIFEIVWSLWNLSRTDIDLSDPEIVRTYLPYLDHVEQHWVRGRGVGWTGNSTLEDCDTTSVAYDVLSKFGRSPDIGAVLQFEDADWFRTYFHEVGPSISTNVHVLGALKQAGYDKCHPRVRKVLEFIRSSKEPGRFCWRDKWHRSAYYTTAHLICAASNYDDALCSDAIGWILNTQRPDGSWGFFDGQATAEETAYCIQALAHWQRHSGTSLSAQISRAGGWLSQHCEPPYAPLWIAKTLYCSATVVKAAILSALRLVDESNQ