Rv2256c Still unknown · low auto-curated
H37Rv Rv2256c · MTBC0 - ·
177 aa · 2529341–2529874 (-) ·
RefSeq NP_216772.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF3145. Function unknown. Foldseek best (non-significant) hit: 6bwo-assembly1_A LarC2, the C-terminal domain of a cyclometallase invo (prob 0.77, TM 0.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O53530
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF3145 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3145) |
| Orthologous group | 299E4 |
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 | 0.115 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF3145 | PF11343.14 | 3.8e-68 | 21–174 | Protein of unknown function (DUF3145) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 79.7 (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 |
|---|---|---|---|---|
6bwo-assembly1_A |
0.77 | 0.32 | 3.3e-03 sig | 6bwo-assembly1_A LarC2, the C-terminal domain of a cyclometallase involved in the synthesis of the NPN cofactor of lactate racemase, apo form |
2cz4-assembly1_C |
0.60 | 0.62 | 5.7e-01 | 2cz4-assembly1_C Crystal structure of a putative PII-like signaling protein (TTHA0516) from Thermus thermophilus HB8 |
7r2y-assembly1_A |
0.60 | 0.60 | 3.9e-01 | 7r2y-assembly1_A Carbon regulatory PII-like protein SbtB from Synechocystis sp. 6803 in complex with ATP resulting from short ATP soak, conflicting T-loop and C-loop with partial occupancy |
3ab2-assembly1_A |
0.57 | 0.49 | 1.6e-01 | 3ab2-assembly1_A Crystal structure of aspartate kinase from Corynebacterium glutamicum in complex with threonine |
3ab2-assembly3_L |
0.51 | 0.46 | 1.2e-01 | 3ab2-assembly3_L Crystal structure of aspartate kinase from Corynebacterium glutamicum in complex with threonine |
2cz4-assembly1_B |
0.41 | 0.60 | 1.0e+00 | 2cz4-assembly1_B Crystal structure of a putative PII-like signaling protein (TTHA0516) from Thermus thermophilus HB8 |
3ab2-assembly2_E |
0.41 | 0.41 | 1.0e-01 | 3ab2-assembly2_E Crystal structure of aspartate kinase from Corynebacterium glutamicum in complex with threonine |
2nzc-assembly1_C |
0.38 | 0.66 | 1.6e+00 | 2nzc-assembly1_C The structure of uncharacterized protein TM1266 from Thermotoga maritima. |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2146c (transmembrane protein), high confidence from genomic context alone (score 774 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) |
|---|---|---|---|---|
Rv2146c |
transmembrane protein | 773 | 774 ctx | cooccurence:763 |
Rv2257c hyp |
hypothetical protein | 759 | 760 ctx | neighborhood:759 |
Rv2699c hyp |
hypothetical protein | 751 | 752 ctx | cooccurence:750 |
Rv2680 hyp |
hypothetical protein | 743 | 733 ctx | cooccurence:728 |
Rv2413c hyp |
hypothetical protein | 706 | 706 ctx | cooccurence:705 |
Rv2033c hyp |
hypothetical protein | 704 | 705 ctx | cooccurence:702 |
Rv1830 |
HTH-type transcriptional regulator | 693 | 694 ctx | cooccurence:689 |
Rv2050 rbpA |
RNA polymerase-binding protein RbpA | 692 | 693 ctx | cooccurence:689 |
Rv3258c hyp |
hypothetical protein | 698 | 687 ctx | cooccurence:670 |
Rv0004 hyp |
hypothetical protein | 686 | 686 ctx | cooccurence:685 |
Rv1423 whiA |
transcriptional regulator WhiA | 683 | 683 ctx | cooccurence:681 |
Rv1087A |
Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT | 683 | 683 ctx | cooccurence:683 |
Rv3683 hyp |
hypothetical protein | 680 | 681 ctx | cooccurence:679 |
Rv2917 hyp |
hypothetical protein | 654 | 654 ctx | cooccurence:654 |
Rv2260 hyp |
hypothetical protein | 645 | 645 ctx | neighborhood:644 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF3145 PF11343.14 (E=4e-68)
- Foldseek best: 6bwo-assembly1_A LarC2, the C-terminal domain of a cyclometallase involved in th (prob 0.77, E=3e-03, TM=0.32)
- (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_216772.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3145 (PF11343.14)
- 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
299E4 - Curated reference: UniProt O53530 (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 79.7, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
47 functional partner(s); context anchor
Rv2146c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2256c| MEPKEQQMRASNQFADVTSGVVYIHASPAAVCPHVEWALSSTLQAKANLVWTPQPALPPQLRAVTNWVGPVGTGARLANALRSWSVLRFEVTEDPSPGVDGQRFSHTPQLGLWSGAMSANGDIMVGEMRLRAMMAQGADTLAAELDSVLGTAWDQALEVYRDGGDAGEVTWLSRGVG