lucA Resolved · high auto-curated
H37Rv Rv3723 · MTBC0 mtbc0_003948 ·
254 aa · 4192657–4193421 (+) ·
RefSeq NP_218240.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | lipid uptake coordinator LucA |
| Revised (this work) | Lipid uptake coordinator LucA. Pfam: LUCA (PF26307.1). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69690
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipid uptake coordinator A |
| Curated function | Required for the import of both fatty acids and cholesterol during growth in macrophages and in axenic culture. Facilitates the uptake of these lipids by stabilizing protein subunits of the Mce1 and Mce4 multi-subunit transporters, which transport fatty acids and cholesterol, respectively. Required for full virulence in vivo. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2AKY4 |
|---|---|
| Gene Ontology (12) |
GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0044425, GO:0044459, GO:0044464, GO:0071944
|
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 | 0.716 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 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 |
|---|---|---|---|---|
LUCA | PF26307.1 | 1.3e-68 | 3–137 | Lipid uptake coordinator A family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cut5b (Rv3724B, (MTV025.072), len: 187 aa. Probable cut5b,truncated cutinase, similar to C-terminal end of others e.g. Q9XB09|RVD2-RV1758 protein (), medium confidence from genomic context alone (score 468 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3722c hyp |
hypothetical protein | 510 | 510 ctx | neighborhood:507 |
Rv3724B cut5b |
Rv3724B, (MTV025.072), len: 187 aa. Probable cut5b,truncated cutinase, similar to C-terminal end of others e.g. Q9XB09|RVD2-RV1758 protein ( | 468 | 468 ctx | neighborhood:463 |
Rv3724A cut5a |
Rv3724A, (MTV025.072), len: 80 aa. Probable cut5a,truncated cutinase precursor, similar to N-terminal end of others e.g. Q9KK87 serine ester | 468 | 468 ctx | neighborhood:463 |
Rv2219 |
transmembrane protein | 442 | 55 | textmining:434 |
Rv0547c |
oxidoreductase | 861 | 50 | textmining:860 |
Rv1013 pks16 |
polyketide synthase | 439 | 50 | textmining:434 |
Rv3499c mce4A |
Mce family protein Mce4A | 650 | 47 | textmining:648 |
Rv1226c |
transmembrane protein | 436 | 47 | textmining:433 |
Rv0587 yrbE2A hyp |
hypothetical protein | 808 | 44 | textmining:808 |
Rv3445c esxU |
ESAT-6 like protein EsxU | 441 | 44 | textmining:440 |
Rv3234c tgs3 |
diacyglycerol O-acyltransferase | 435 | 44 | textmining:434 |
Rv1964 yrbE3A |
integral membrane protein | 403 | 44 | textmining:402 |
Rv3484 cpsA hyp |
hypothetical protein | 436 | 42 | textmining:436 |
Rv2308 hyp |
hypothetical protein | 860 | 41 | textmining:860 |
Rv1414 hyp |
hypothetical protein | 860 | 41 | textmining:860 |
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: transmembrane protein
- MTBC0 PGAP product: lipid uptake coordinator LucA
- Pfam (hmmscan --cut_ga): LUCA PF26307.1 (E=1e-68)
- (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_218240.1)
- Domains: Pfam-A via hmmscan --cut_ga — LUCA (PF26307.1)
- 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
2AKY4 - Curated reference: UniProt O69690 (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 —
17 functional partner(s); context anchor
cut5b - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003948|Rv3723|lucA MGRKVAVLWHASFSIGAGVLYFYFVLPRWPELMGDTGHSLGTGLRIATGALVGLAALPVVFTLLRTRKPELGTPQLALSMRIWSIMAHVLAGALIVGTAISEVWLSLDAAGQWLFGIYGAAAAIAVLGFFGFYLSFVAELPPPPPKPLKPKKPKQRRLRRKKTAKGDEAEPEAAEEAENTELAAQEDEEAVEAPPESIESPGGEPESATREAPAAETATAEEPRGGLRNRRPTGKTSHRRRRTRSGVQVAKVDE