lipA Resolved · high auto-curated
H37Rv Rv2218 · MTBC0 mtbc0_002354 ·
311 aa · 2511430–2512365 (+) ·
RefSeq NP_216734.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoyl synthase |
|---|---|
| MTBC0 PGAP re-annotation | lipoyl synthase |
| Revised (this work) | Lipoyl synthase. Pfam: LIAS_N (PF16881.11), Radical_SAM (PF04055.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK91
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipoyl synthase |
| EC (curated) |
EC 2.8.1.8
|
| Curated function | Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | lipA |
| eggNOG description | Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives |
| Orthologous group | COG0320 |
| EC number |
EC 2.8.1.8
|
| KEGG orthology |
K03644
|
| KEGG pathways |
map00785, map01100
|
| Gene Ontology (64) |
GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006464, GO:0006629, GO:0006631, GO:0006633, GO:0006732 +52 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 | 0.089 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 1 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 |
|---|---|---|---|---|
LIAS_N | PF16881.11 | 8.8e-09 | 18–60 | N-terminal domain of lipoyl synthase of Radical_SAM family |
Radical_SAM | PF04055.28 | 6.5e-19 | 78–233 | Radical SAM superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipB (octanoyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2217 lipB |
octanoyltransferase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:762 database:900 textmining:892 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 949 | 921 ctx | neighborhood:808 cooccurence:591 |
Rv1826 gcvH |
glycine cleavage system protein H | 939 | 921 | database:844 |
Rv2219 |
transmembrane protein | 846 | 847 ctx | neighborhood:843 |
Rv2216 |
epimerase family protein | 839 | 810 ctx | neighborhood:808 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 797 | 623 ctx | cooccurence:590 textmining:486 |
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 573 | 540 ctx | cooccurence:490 |
Rv1449c tkt |
transketolase | 515 | 515 | coexpression:451 |
Rv1832 gcvB |
glycine dehydrogenase | 634 | 484 | |
Rv2535c pepQ |
cytoplasmic peptidase PepQ | 447 | 448 | database:424 |
Rv2089c pepE |
dipeptidase PepE | 443 | 443 | database:424 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 469 | 427 | |
Rv2440c obg |
GTPase Obg | 438 | 413 | |
Rv2214c ephD |
oxidoreductase EphD | 436 | 408 ctx | neighborhood:400 |
Rv2211c gcvT |
aminomethyltransferase | 470 | 406 |
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: lipoyl synthase
- MTBC0 PGAP product: lipoyl synthase
- Pfam (hmmscan --cut_ga): LIAS_N PF16881.11 (E=9e-09), Radical_SAM PF04055.28 (E=7e-19)
- (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_216734.1)
- Domains: Pfam-A via hmmscan --cut_ga — LIAS_N (PF16881.11), Radical_SAM (PF04055.28)
- 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
COG0320 - Curated reference: UniProt P9WK91 (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 —
34 functional partner(s); context anchor
lipB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002354|Rv2218|lipA MSVAAEGRRLLRLEVRNAQTPIERKPPWIKTRARIGPEYTELKNLVRREGLHTVCEEAGCPNIFECWEDREATFLIGGDQCTRRCDFCQIDTGKPAELDRDEPRRVADSVRTMGLRYATVTGVARDDLPDGGAWLYAATVRAIKELNPSTGVELLIPDFNGEPTRLAEVFESGPEVLAHNVETVPRIFKRIRPAFTYRRSLGVLTAARDAGLVTKSNLILGLGETSDEVRTALGDLRDAGCDIVTITQYLRPSARHHPVERWVKPEEFVQFARFAEGLGFAGVLAGPLVRSSYRAGRLYEQARNSRALASR