lipJ Family assigned · medium auto-curated
H37Rv Rv1900c · MTBC0 mtbc0_002015 ·
462 aa · 2164355–2165743 (-) ·
RefSeq NP_216416.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lignin peroxidase LipJ |
|---|---|
| MTBC0 PGAP re-annotation | adenylate/guanylate cyclase domain-containing protein |
| Revised (this work) | Adenylate/guanylate cyclase domain-containing protein. Pfam: Abhydrolase_1 (PF00561.27), Guanylate_cyc (PF00211.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07732
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional lipase/adenylate cyclase LipJ [Includes: Lipase |
| EC (curated) |
EC 3.1.1.-, EC 4.6.1.1
|
| Curated function | May play a role in cell wall modulation. The N-terminal domain exhibits lipolytic activity. In vitro, hydrolyzes various p-nitrophenyl (pNP) esters. pNP-decanoate (C10) is the best substrate, followed by pNP-octonate (C8), pNP-laurate (C12) and pNP-butyrate (C4). Exhibits lower activity with pNP-acetate (C2), pNP-myristate (C14) and pNP-palmitate (C16). Can also use tributyrin. The C-terminal domain catalyzes the biosynthesis of cyclic AMP (cAMP) from ATP. It has a guanylyl cyclase side-activity, corresponding to 7% of the adenylate cyclase activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismT Signal transduction mechanisms
|
|---|---|
| Preferred name | lipJ |
| eggNOG description | PFAM Adenylate and Guanylate cyclase catalytic domain |
| Orthologous group | COG2114 |
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 | 1.747 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 10 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.50% of strains (727) · 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 |
|---|---|---|---|---|
Abhydrolase_1 | PF00561.27 | 2.5e-08 | 63–158 | alpha/beta hydrolase fold |
Guanylate_cyc | PF00211.26 | 1.2e-11 | 296–445 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lppD (lipoprotein LppD), high confidence from genomic context alone (score 788 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1899c lppD |
lipoprotein LppD | 789 | 788 ctx | neighborhood:780 |
Rv1901 cinA |
competence damage-inducible protein CinA | 692 | 693 ctx | neighborhood:686 |
Rv1363c |
membrane protein | 646 | 633 | |
Rv1359 |
transcriptional regulator | 603 | 603 ctx | cooccurence:603 |
Rv2048c pks12 |
polyketide synthase | 637 | 593 | experimental:455 |
Rv0199 |
membrane protein | 601 | 586 | |
Rv3492c |
Mce associated protein | 600 | 584 | |
Rv0200 |
transmembrane protein | 600 | 584 | |
Rv0178 |
Mce associated membrane protein | 598 | 583 | |
Rv1972 |
Mce associated membrane protein | 598 | 582 | |
Rv2390c hyp |
hypothetical protein | 597 | 582 | |
Rv1362c |
membrane protein | 597 | 582 | |
Rv1973 |
Mce associated membrane protein | 597 | 582 | |
Rv0177 |
Mce associated protein | 597 | 582 | |
Rv1902c nanT |
sialic acid-transport integral membrane protein NanT | 545 | 545 ctx | neighborhood:541 |
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: lignin peroxidase LipJ
- MTBC0 PGAP product: adenylate/guanylate cyclase domain-containing protein
- Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=2e-08), Guanylate_cyc PF00211.26 (E=1e-11)
- (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_216416.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Guanylate_cyc (PF00211.26)
- 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
COG2114 - Curated reference: UniProt O07732 (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 —
61 functional partner(s); context anchor
lppD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002015|Rv1900c|lipJ MAQAPHIHRTRYAKCGDMDIAYQVLGDGPTDLLVLPGPFVPIDSIDDEPSLYRFHRRLASFSRVIRLDHRGVGLSSRLAAITTLGPKFWAQDAIAVMDAVGCEQATIFAPSFHAMNGLVLAADYPERVRSLIVVNGSARPLWAPDYPVGAQVRRADPFLTVALEPDAVERGFDVLSIVAPTVAGDDVFRAWWDLAGNRAGPPSMARAVSKVIAEADVRDVLGHIEAPTLILHRVGSTYIPVGHGRYLAEHIAGSRLVELPGTDTLYWVGDTGPMLDEIEEFITGVRGGADAERMLATIMFTDIVGSTQHAAALGDDRWRDLLDNHDTIVCHEIQRFGGREVNTAGDGFVATFTSPSAAIACADDIVDAVAALGIEVRIGIHAGEVEVRDASHGTDVAGVAVHIGARVCALAGPSEVLVSSTVRDIVAGSRHRFAERGEQELKGVPGRWRLCVLMRDDATRTR