Rv2044c Family assigned · low
H37Rv Rv2044c · MTBC0 - ·
105 aa · 2289282–2289599 (-) ·
RefSeq NP_216560.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polytopic integral membrane protein with 3 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
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 |
O53487
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | DUF2784 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of Unknown function (DUF2784) |
| Orthologous group | 2CNK3 |
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 6.00% of strains (8707) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF2784 | PF10861.14 | 2.4e-31 | 1–99 | Protein of Unknown function (DUF2784) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipT (carboxylesterase LipT), high confidence from genomic context alone (score 785 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) |
|---|---|---|---|---|
Rv2045c lipT |
carboxylesterase LipT | 785 | 785 ctx | neighborhood:782 |
Rv2042c hyp |
hypothetical protein | 958 | 692 ctx | neighborhood:690 textmining:870 |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 888 | 691 ctx | neighborhood:690 textmining:652 |
Rv2041c |
sugar ABC transporter substrate-binding lipoprotein | 578 | 577 ctx | neighborhood:571 |
Rv2039c |
sugar ABC transporter permease | 576 | 576 ctx | neighborhood:558 |
Rv2038c ugpC |
sugar ABC transporter ATP-binding protein | 569 | 569 ctx | neighborhood:558 |
Rv2040c |
sugar ABC transporter permease | 569 | 568 ctx | neighborhood:558 |
Rv2037c |
transmembrane protein | 555 | 555 ctx | neighborhood:550 |
Rv3397c phyA |
phytoene synthase | 544 | 545 ctx | neighborhood:544 |
Rv3091 hyp |
hypothetical protein | 511 | 511 ctx | cooccurence:511 |
Rv2046 lppI |
lipoprotein LppI | 483 | 482 ctx | neighborhood:480 |
Rv2695 hyp |
hypothetical protein | 410 | 411 ctx | cooccurence:407 |
Rv2307c hyp |
hypothetical protein | 409 | 410 | |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 512 | 41 | textmining:512 |
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
- DeepTMHMM: 3 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular 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_216560.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2784 (PF10861.14)
- 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
2CNK3 - Curated reference: UniProt O53487 (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 82.4, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
14 functional partner(s); context anchor
lipT - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2044c| MHFAFIAYVLAGGFLALRWRRTMWLHVPAVIWGIGIAAKRVDCPLTWVERWARTKAAMTPLSPDGFVAHYITGVIYPAGWVAAAQLVMFAIVAASWTLYLWLPRR