Rv2033c Still unknown · low
H37Rv Rv2033c · MTBC0 mtbc0_002166 ·
280 aa · 2308853–2309695 (-) ·
RefSeq NP_216549.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3097 domain-containing protein |
| Revised (this work) | DUF3097; Foldseek best hit (OLD protein, TM 0.49) not conclusive. Function unknown. |
Curated reference (UniProt)
| UniProt |
O53477
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF3097 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3097) |
| Orthologous group | COG0613 |
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, 4 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 |
|---|---|---|---|---|
DUF3097_N | PF22845.3 | 2.8e-25 | 22–80 | DUF3097, N-terminal domain |
DUF3097_C | PF11296.15 | 2.1e-76 | 109–275 | DUF3097, C-terminal domain |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.5 (very high). 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 |
|---|---|---|---|---|
6nk8-assembly1_A-2 |
1.00 | 0.49 | 6.6e-04 sig | 6nk8-assembly1_A-2 C-terminal region of the Burkholderia pseudomallei OLD protein |
6nk8-assembly1_B-2 |
0.99 | 0.44 | 1.7e-03 sig | 6nk8-assembly1_B-2 C-terminal region of the Burkholderia pseudomallei OLD protein |
6zye-assembly1_E |
0.97 | 0.77 | 2.4e-01 | 6zye-assembly1_E YnaI in an open-like conformation |
6cer-assembly1_D |
0.89 | 0.44 | 1.1e-02 | 6cer-assembly1_D Human pyruvate dehydrogenase complex E1 component V138M mutation |
3ezx-assembly1_A |
0.84 | 0.50 | 3.4e-02 | 3ezx-assembly1_A Structure of Methanosarcina barkeri monomethylamine corrinoid protein |
6urt-assembly1_G |
0.77 | 0.76 | 9.5e-01 | 6urt-assembly1_G Extended Sensor Paddles with Bound Lipids Revealed in Mechanosensitive Channel YnaI |
5y4o-assembly1_A |
0.75 | 0.74 | 1.0e+00 | 5y4o-assembly1_A Cryo-EM structure of MscS channel, YnaI |
2coy-assembly1_A |
0.57 | 0.48 | 3.3e-01 | 2coy-assembly1_A Solution structure of the CAP-Gly domain in human Dynactin 1 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2034 (ArsR family HTH-type transcriptional repressor), medium confidence from genomic context alone (score 548 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) |
|---|---|---|---|---|
Rv2917 hyp |
hypothetical protein | 754 | 755 ctx | cooccurence:752 |
Rv2256c hyp |
hypothetical protein | 704 | 705 ctx | cooccurence:702 |
Rv2035 hyp |
hypothetical protein | 628 | 549 ctx | neighborhood:546 |
Rv2036 hyp |
hypothetical protein | 769 | 548 ctx | neighborhood:546 textmining:511 |
Rv2034 |
ArsR family HTH-type transcriptional repressor | 606 | 548 ctx | neighborhood:546 |
Rv3258c hyp |
hypothetical protein | 528 | 528 ctx | cooccurence:505 |
Rv1321 nucS |
endonuclease NucS | 497 | 498 ctx | cooccurence:495 |
Rv2680 hyp |
hypothetical protein | 474 | 475 ctx | cooccurence:467 |
Rv3260c whiB2 |
transcriptional regulator WhiB2 | 472 | 473 ctx | cooccurence:465 |
Rv1301 |
threonylcarbamoyl-AMP synthase | 440 | 440 | |
Rv1830 |
HTH-type transcriptional regulator | 431 | 432 ctx | cooccurence:427 |
Rv1087A |
Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT | 428 | 428 ctx | cooccurence:408 |
Rv2146c |
transmembrane protein | 426 | 426 ctx | cooccurence:424 |
Rv2711 ideR |
iron-dependent repressor and activator IdeR | 422 | 423 | |
Rv2745c clgR |
transcriptional regulator ClgR | 414 | 415 |
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
- MTBC0 PGAP product: DUF3097 domain-containing protein
- Pfam: DUF3097_N PF22845.3, DUF3097_C PF11296.15
- Foldseek best: 6nk8-assembly1_A-2 C-terminal region of the Burkholderia pseudomallei OLD protei (prob 1.00, E=7e-04, TM=0.49)
- (structure-only promotion reviewed by hand, 2026-06-01)
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_216549.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3097_N (PF22845.3), DUF3097_C (PF11296.15)
- 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
COG0613 - Curated reference: UniProt O53477 (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 95.5, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
25 functional partner(s); context anchor
Rv2034 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002166|Rv2033c| MLDRYGTDVLAAGGRRRPRSVEHPVELGMVVEDAETGYVGAVVRVEYGRIDLEDRYGKTRGFPLGPGYLLDGLPVILTAPRCAAAAGPRRTASGSVAVPGARARVARASRIYVEGRHDAELIAAVWGADLRIEGVVVEHLGGVDDLVEIVAKFRPGPRRRLGVLVDHLVAGSKEARIAEVVRRGPGGSDTLVVGHPYVDIWQAVKPQRVGLAAWPRVPRHIEWKHGVCDALGWPHADQADIAAAWRRIRSQVRDWTDLEPALIGRVEELIDFVTQPAGDE