ltp2 Resolved · high auto-curated
H37Rv Rv3540c · MTBC0 mtbc0_003757 ·
386 aa · 4003176–4004336 (-) ·
RefSeq NP_218057.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipid transfer protein |
|---|---|
| MTBC0 PGAP re-annotation | lipid-transfer protein |
| Revised (this work) | Lipid-transfer protein. Pfam: Thiolase_N (PF00108.30), Thiolase_C_1 (PF22691.3). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y3T7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA lyase |
| EC (curated) |
EC 4.1.3.-
|
| Curated function | Involved in cholesterol side chain degradation. When associated with the ChsH1/ChsH2 hydratase, catalyzes the retroaldol cleavage of 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA) produced by the hydratase, forming androst-4-ene-3,17-dione and propionyl-CoA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | ltp2 |
| eggNOG description | lipid-transfer protein |
| Orthologous group | COG0183 |
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 | 0.208 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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 |
|---|---|---|---|---|
Thiolase_N | PF00108.30 | 1.1e-06 | 8–227 | Thiolase, N-terminal domain |
Thiolase_C_1 | PF22691.3 | 8.6e-29 | 271–378 | Thiolase C-terminal domain-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE29 (acyl-CoA dehydrogenase FadE29), high confidence from genomic context alone (score 980 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3542c chsH2 hyp |
hypothetical protein | 999 | 999 ctx | neighborhood:882 cooccurence:761 coexpression:866 experimental:508 database:500 |
Rv3541c chsH1 hyp |
hypothetical protein | 999 | 998 ctx | neighborhood:882 cooccurence:730 coexpression:857 database:500 textmining:809 |
Rv3543c fadE29 |
acyl-CoA dehydrogenase FadE29 | 998 | 980 ctx | neighborhood:881 cooccurence:602 coexpression:577 textmining:907 |
Rv0860 fadB |
fatty oxidation protein FadB | 969 | 966 | coexpression:697 experimental:804 database:447 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 995 | 962 ctx | neighborhood:881 cooccurence:476 textmining:878 |
Rv3521 hyp |
hypothetical protein | 916 | 895 ctx | cooccurence:706 coexpression:424 experimental:415 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 907 | 877 ctx | cooccurence:526 database:447 |
Rv3545c cyp125 |
steroid C26-monooxygenase | 980 | 865 ctx | neighborhood:836 textmining:865 |
Rv3562 fadE31 |
acyl-CoA dehydrogenase FadE31 | 843 | 834 ctx | cooccurence:716 |
Rv3560c fadE30 |
acyl-CoA dehydrogenase FadE30 | 915 | 826 ctx | cooccurence:701 textmining:535 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 848 | 815 ctx | cooccurence:546 database:500 |
Rv3551 |
CoA-transferase subunit alpha | 846 | 805 ctx | cooccurence:753 |
Rv3552 |
CoA-transferase subunit beta | 813 | 805 ctx | cooccurence:750 |
Rv3516 echA19 |
enoyl-CoA hydratase EchA19 | 859 | 785 | database:447 |
Rv3573c fadE34 |
acyl-CoA dehydrogenase FadE34 | 924 | 783 ctx | cooccurence:628 textmining:668 |
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: lipid transfer protein
- MTBC0 PGAP product: lipid-transfer protein
- Pfam (hmmscan --cut_ga): Thiolase_N PF00108.30 (E=1e-06), Thiolase_C_1 PF22691.3 (E=9e-29)
- (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_218057.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thiolase_N (PF00108.30), Thiolase_C_1 (PF22691.3)
- 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
COG0183 - Curated reference: UniProt I6Y3T7 (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 —
124 functional partner(s); context anchor
fadE29 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003757|Rv3540c|ltp2 MLSGQAAIVGIGATDFSKNSGRSELRLAAEAVLDALADAGLSPTDVDGLTTFTMDTNTEIAVARAAGIGELTFFSKIHYGGGAACATVQHAAMAVATGVADVVVAYRAFNERSGMRFGQVQTRLTENADSTGVDNSFSYPHGLSTPAAQVAMIARRYMHLSGATSRDFGAVSVADRKHAANNPKAYFYGKPITIEDHQNSRWIAEPLRLLDCCQETDGAVAIVVTSAARARDLKQRPVVIEAAAQGCSPDQYTMVSYYRPELDGLPEMGLVGRQLWAQSGLTPADVQTAVLYDHFTPFTLIQLEELGFCGKGEAKDFIADGAIEVGGRLPINTHGGQLGEAYIHGMNGIAEGVRQLRGTSVNPVAGVEHVLVTAGTGVPTSGLILG