Rv2253 Family assigned · medium
H37Rv Rv2253 · MTBC0 mtbc0_002395 ·
167 aa · 2554144–2554647 (+) ·
RefSeq NP_216769.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Membrane protein with a PknI-sensor-domain-like extracytoplasmic sensor fold; distinct from PknI/Rv2914c (fold-paralogue safeguard). Same sensor fold as Rv3491. |
Curated reference (UniProt)
| UniProt |
O53527
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BFCU |
|---|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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)
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 84.5 (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 |
|---|---|---|---|---|
5xlm-assembly1_A |
1.00 | 0.69 | 4.7e-07 sig | 5xlm-assembly1_A Monomer form of M.tuberculosis PknI sensor domain |
5xlm-assembly2_B |
1.00 | 0.63 | 2.0e-06 sig | 5xlm-assembly2_B Monomer form of M.tuberculosis PknI sensor domain |
5xll-assembly1_A |
1.00 | 0.64 | 5.5e-05 sig | 5xll-assembly1_A Dimer form of M. tuberculosis PknI sensor domain |
2cwz-assembly2_D |
0.21 | 0.42 | 4.4e-01 | 2cwz-assembly2_D Crystal structure of the Thermus thermophilus hypothetical protein TTHA0967, a thioesterase superfamily member |
2m07-assembly1_A |
0.21 | 0.35 | 5.5e-01 | 2m07-assembly1_A NMR structure of OmpX in DPC micelles |
5vj8-assembly1_A |
0.21 | 0.34 | 4.6e-01 | 5vj8-assembly1_A Backbone structure of the Yersinia pestis outer membrane protein Ail in phospholipid bilayer nanodisc |
1q9g-assembly1_A |
0.20 | 0.32 | 2.2e-01 | 1q9g-assembly1_A NMR STRUCTURE OF THE OUTER MEMBRANE PROTEIN OMPX IN DHPC MICELLES |
5hqw-assembly1_A |
0.16 | 0.35 | 3.0e-01 | 5hqw-assembly1_A Crystal structure of a trans-AT PKS dehydratase domain of C0ZGQ6 from Brevibacillus brevis |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dagK (diacylglycerol kinase), high confidence from genomic context alone (score 799 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) |
|---|---|---|---|---|
Rv2252 dagK |
diacylglycerol kinase | 799 | 799 ctx | neighborhood:796 |
Rv2249c glpD1 |
glycerol-3-phosphate dehydrogenase | 711 | 711 ctx | neighborhood:710 |
Rv2251 |
flavoprotein | 613 | 614 ctx | neighborhood:611 |
Rv2250A |
Possible flavoprotein; Rv2250A, len: 139 aa. Conserved hypothetical protein, possibly flavoprotein. Similar to N-terminus of SCF91.28c|AL132 | 613 | 613 ctx | neighborhood:611 |
Rv2250c |
HTH-type transcriptional regulator | 596 | 597 ctx | neighborhood:594 |
Rv0063 |
oxidoreductase | 871 | 55 | textmining:870 |
Rv3705c hyp |
hypothetical protein | 871 | 53 | textmining:870 |
Rv1804c hyp |
hypothetical protein | 870 | 47 | textmining:870 |
Rv0603 hyp |
hypothetical protein | 870 | 47 | textmining:870 |
Rv0519c |
membrane protein | 811 | 47 | textmining:810 |
Rv1810 hyp |
hypothetical protein | 514 | 47 | textmining:511 |
Rv2903c lepB |
signal peptidase | 809 | 45 | textmining:809 |
Rv0203 hyp |
hypothetical protein | 543 | 44 | textmining:542 |
Rv1271c hyp |
hypothetical protein | 870 | 41 | textmining:870 |
Rv1352 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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
- Foldseek vs AFDB-SwissProt: PknI sensor domain, TM 0.64, E 1e-9 (PknI = Rv2914c, not this locus)
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
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_216769.1)
- 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
2BFCU - Curated reference: UniProt O53527 (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 84.5, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
16 functional partner(s); context anchor
dagK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002395|Rv2253| MSGHRKKAMLALAAASLAATLAPNAVAAAEPSWNGQYLVTLSANAKTGTSMAANRPEYPHKANYTFSSRCASDVCIATVVDAPPPKNEFIPRPIEYTWNGTQWVREISWQWDCLLPDGTIEYAPAKSITAYTPGQYGILTGVFHTDIASGTCKGNVDMPVSAKPIVG