lppF Resolved · high auto-curated
H37Rv Rv1921c · MTBC0 mtbc0_002035 ·
423 aa · 2191640–2192911 (-) ·
RefSeq NP_216437.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppF |
|---|---|
| MTBC0 PGAP re-annotation | haloacid dehalogenase-like hydrolase |
| Revised (this work) | Haloacid dehalogenase-like hydrolase. Pfam: Hydrolase (PF00702.33), HAD (PF12710.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53963
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | phosphoserine phosphatase |
| EC (curated) |
EC 3.1.3.3
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | lppF |
| eggNOG description | haloacid dehalogenase-like hydrolase |
| Orthologous group | COG0560 |
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 | 1.602 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 10 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 |
|---|---|---|---|---|
Hydrolase | PF00702.33 | 1.8e-06 | 70–265 | haloacid dehalogenase-like hydrolase |
HAD | PF12710.14 | 4.3e-07 | 222–339 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2319c (universal stress protein), medium confidence from genomic context alone (score 531 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1443c hyp |
hypothetical protein | 674 | 674 ctx | cooccurence:674 |
Rv3594 hyp |
hypothetical protein | 623 | 624 ctx | cooccurence:617 |
Rv1978 hyp |
hypothetical protein | 619 | 620 ctx | cooccurence:562 |
Rv1288 hyp |
hypothetical protein | 601 | 602 ctx | cooccurence:533 |
Rv1605 hisF |
imidazole glycerol phosphate synthase subunit HisF | 607 | 581 | coexpression:567 |
Rv2319c |
universal stress protein | 531 | 531 ctx | cooccurence:529 |
Rv1602 hisH |
imidazole glycerol phosphate synthase subunit HisH | 537 | 517 | coexpression:501 |
Rv3882c eccE1 |
ESX-1 secretion system protein EccE1 | 509 | 509 ctx | cooccurence:509 |
Rv2608 PPE42 |
PPE family protein PPE42 | 508 | 508 ctx | cooccurence:501 |
Rv1603 hisA |
1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase | 526 | 504 | coexpression:487 |
Rv1682 hyp |
hypothetical protein | 495 | 495 ctx | cooccurence:492 |
Rv1606 hisI |
phosphoribosyl-AMP cyclohydrolase | 520 | 488 | coexpression:471 |
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 522 | 484 | coexpression:467 |
Rv3879c espK |
ESX-1 secretion-associated protein EspK | 460 | 461 ctx | cooccurence:460 |
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 451 | 452 |
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: lipoprotein LppF
- MTBC0 PGAP product: haloacid dehalogenase-like hydrolase
- Pfam (hmmscan --cut_ga): Hydrolase PF00702.33 (E=2e-06), HAD PF12710.14 (E=4e-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_216437.1)
- Domains: Pfam-A via hmmscan --cut_ga — Hydrolase (PF00702.33), HAD (PF12710.14)
- 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
COG0560 - Curated reference: UniProt O53963 (TrEMBL, unreviewed; Inferred from homology)
- 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
Rv2319c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002035|Rv1921c|lppF MVRLIPSLLAMATVLGGVIGCSAHQPPTPASGCRQLDAFLKWHHGVREFLQSAIDANSRCTGTADGSARKVAIFDWDNTVVKNDIGYATNYYMLQHSLVLQPANQDWHAASRYLTDAAANALSVACGKVVPAGKPLPTGSNALCANEILSLLDGETTTGQPAFVGNNVRRLAGPYAWSNALSAGYTAEELAGFADQAKKQNLAADVGATQQVGTQQVDGYIRVYPQMKDLIGTLQAHGIDTWVVSASPEPIVKVWAGEVGLDDQHVVGVRSVADQSGKLTAHLVGCGGVRDGDDSVMTYLDGKRCWANQVIFGVTGPQAFNQLAADRRQVLAAGDSNSDATFVGDATVVSLVINRNQDDLMCRAYDGLFTRGGKWAINPMFIDPLPQHAPYVCGEAFINPDGSKQPVLRNDGTPIPDQVDSVF