Rv2189c Still unknown · low
H37Rv Rv2189c · MTBC0 mtbc0_002324 ·
257 aa · 2477254–2478027 (-) ·
RefSeq NP_216705.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical; function unknown. Structure-based hint rejected: the real M1 alanyl-aminopeptidase PepN is Rv2467 (paralogue-of-fold). |
Curated reference (UniProt)
| UniProt |
O53523
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | DUF4157 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | aminopeptidase N |
| Orthologous group | COG0308 |
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) pseudogene candidate
| pN/pS | 0.092 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 11.00% of strains (15978) · 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)
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 89.1 (confident). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
4arf-assembly1_A |
1.00 | 0.49 | 4.0e-04 sig | 4arf-assembly1_A CRYSTAL STRUCTURE OF THE PEPTIDASE DOMAIN OF COLLAGENASE H FROM CLOSTRIDIUM HISTOLYTICUM IN COMPLEX WITH THE PEPTIDIC INHIBITOR ISOAMYLPHOSPHONYL-GLY-PRO-ALA AT 1.77 ANGSTROM RESOLUTION. |
4r5t-assembly1_A |
1.00 | 0.53 | 1.7e-03 sig | 4r5t-assembly1_A Structure of the m1 alanylaminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor |
8t83-assembly1_A |
1.00 | 0.52 | 1.6e-03 sig | 8t83-assembly1_A X-ray crystal structure of PfA-M1(M462K) |
6u7f-assembly2_B |
1.00 | 0.53 | 2.5e-03 sig | 6u7f-assembly2_B HCoV-229E RBD Class IV in complex with human APN |
6oiu-assembly4_D |
1.00 | 0.50 | 1.5e-03 sig | 6oiu-assembly4_D X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350) |
2y50-assembly1_A |
1.00 | 0.49 | 2.8e-03 sig | 2y50-assembly1_A Crystal Structure of Collagenase G from Clostridium histolyticum at 2. 80 Angstrom Resolution |
6oiu-assembly3_C |
1.00 | 0.51 | 4.7e-03 sig | 6oiu-assembly3_C X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350) |
4are-assembly1_A |
1.00 | 0.47 | 2.8e-03 sig | 4are-assembly1_A Crystal structure of the collagenase Unit of collagenase G from Clostridium histolyticum at 2.19 angstrom resolution. |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ripC (endopeptidase), high confidence from genomic context alone (score 791 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) |
|---|---|---|---|---|
Rv2190c ripC |
endopeptidase | 798 | 791 ctx | neighborhood:752 |
Rv2188c pimB |
alpha-(1-6)-phosphatidylinositol monomannoside mannosyltransferase | 779 | 780 ctx | neighborhood:775 |
Rv3446c hyp |
hypothetical protein | 677 | 657 ctx | cooccurence:599 |
Rv1362c |
membrane protein | 660 | 645 ctx | cooccurence:594 |
Rv0651 rplJ |
50S ribosomal protein L10 | 634 | 621 | database:546 |
Rv0513 |
transmembrane protein | 618 | 619 ctx | cooccurence:613 |
Rv1363c |
membrane protein | 625 | 608 ctx | cooccurence:552 |
Rv0250c hyp |
hypothetical protein | 606 | 607 ctx | cooccurence:603 |
Rv0703 rplW |
50S ribosomal protein L23 | 612 | 603 | database:546 |
Rv0715 rplX |
50S ribosomal protein L24 | 600 | 601 | database:546 |
Rv3339c icd1 |
isocitrate dehydrogenase | 626 | 590 | database:526 |
Rv3068c pgmA |
phosphoglucomutase PgmA | 611 | 588 | database:519 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 590 | 566 | database:486 |
Rv1972 |
Mce associated membrane protein | 583 | 564 ctx | cooccurence:503 |
Rv0174 mce1F |
Mce family protein Mce1F | 562 | 562 ctx | cooccurence:550 |
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
- Structural Foldseek hit not propagated -- the real M1 alanyl-aminopeptidase PepN is Rv2467 (paralogue-of-fold)
- Reviewed against literature (extended structural cross-check, 2026-06-02)
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_216705.1)
- 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
COG0308 - Curated reference: UniProt O53523 (TrEMBL, unreviewed; Predicted)
- 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 89.1, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
66 functional partner(s); context anchor
ripC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002324|Rv2189c| MRDGPAAPAQVVAPADGFVALRVADDRTVRLLSLGGAATDRLLSRIAAGIDAAVDEVVAFWGTDWSHDIFVVAAGSDEQFHAAAGGGLASQWADIAAITVVDRVDPARRTVVGQRIVFAPGAAHMSPAALRIVLGHELFHYAARADTALDAPRWLAEGVADFVARPKTPPPADAVSVALSLPSDTDLDTPGPQRSLAYDRAWWFARFVAAAYGTAKLRELYLATCGVGHFDLATAAHDVLGIDAAGLLARWQRWLMG