Rv0381c Still unknown · low auto-curated
H37Rv Rv0381c · MTBC0 mtbc0_000401 ·
302 aa · 460277–461185 (-) ·
RefSeq NP_214895.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 4j51-assembly2_B Cyrstal structure of protein tyrosine phosphatase Lyp (prob 0.33, TM 0.63). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53716
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipoprotein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 29ENA |
|---|
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 | 0.188 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 63.6 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
4j51-assembly2_B |
0.33 | 0.63 | 7.6e-01 | 4j51-assembly2_B Cyrstal structure of protein tyrosine phosphatase Lyp catalytic domain complex with small molecular inhibitor L75N04 |
2p6x-assembly1_A |
0.30 | 0.63 | 8.1e-01 | 2p6x-assembly1_A Crystal structure of human tyrosine phosphatase PTPN22 |
2p6x-assembly2_B |
0.25 | 0.62 | 1.1e+00 | 2p6x-assembly2_B Crystal structure of human tyrosine phosphatase PTPN22 |
3omh-assembly3_C |
0.23 | 0.62 | 1.3e+00 | 3omh-assembly3_C Crystal structure of PTPN22 in complex with SKAP-HOM pTyr75 peptide |
3brh-assembly1_A |
0.21 | 0.52 | 7.6e-01 | 3brh-assembly1_A Protein Tyrosine Phosphatase PTPN-22 (Lyp) bound to the mono-Phosphorylated Lck active site peptide |
4rh9-assembly1_A |
0.20 | 0.67 | 3.1e+00 | 4rh9-assembly1_A Crystal structure of PTPN3 (PTPH1) H812F, M883G mutant in complex with Eps15 pTyr849 peptide |
4rhg-assembly1_A |
0.20 | 0.67 | 3.1e+00 | 4rhg-assembly1_A Crystal structure of PTPN3 (PTPH1) D811E, C842S mutant in complex with Eps15 pTyr849 peptide |
1ygu-assembly1_A |
0.20 | 0.68 | 2.6e+00 | 1ygu-assembly1_A Crystal structure of the tandem phosphatase domains of RPTP CD45 with a pTyr peptide |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pyrE (orotate phosphoribosyltransferase), high confidence from genomic context alone (score 867 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0382c pyrE |
orotate phosphoribosyltransferase | 867 | 867 ctx | neighborhood:863 |
Rv0380c |
RNA methyltransferase | 775 | 776 ctx | neighborhood:776 |
Rv0383c ttfA hyp |
hypothetical protein | 773 | 774 ctx | neighborhood:774 |
Rv0384c clpB |
chaperone protein ClpB | 692 | 692 ctx | neighborhood:691 |
Rv0365c hyp |
hypothetical protein | 550 | 551 ctx | neighborhood:544 |
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: hypothetical protein
- MTBC0 PGAP product: hypothetical protein
- Foldseek best: 4j51-assembly2_B Cyrstal structure of protein tyrosine phosphatase Lyp catalytic (prob 0.33, E=8e-01, TM=0.63)
- (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_214895.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
29ENA - Curated reference: UniProt O53716 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 63.6, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
5 functional partner(s); context anchor
pyrE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000401|Rv0381c| MRILVAWATCGAVVLSGLTGCSGSSHSGRTYGAQSARTGESLAVLGWNMSVSNLRWSGDYVLIDVDASPTDPHAPHAKPEDIRFGLYGALAHPMESAALGSCGDAMAHVRDVVSPLSAPAGRLTGTVCLGPLKERSAVRGVYTYSPRDRIPGTAAAYPAAFPVGMLPTNQNDAGLVVKTTSVSAWRADGMQLGKPQLGDPVAFTGNGYMLLGLEVDAVPDRYRDDSAARGGPMMLLAAPTLPGRGLSPACATYGSSVLILPDALLDAVHISASLCTQGEINEALLYATVATVGTHAALWTSR