Rv2348c Still unknown · low
H37Rv Rv2348c · MTBC0 mtbc0_002500 ·
108 aa · 2651404–2651730 (-) ·
RefSeq NP_216864.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | T-cell-stimulating antigen used (with EspC and EspF) in an ESAT-6-free IGRA; a non-synonymous variant (I101M) shows a genome-to-genome association with human PRDM15. Despite this immunological/genetic characterisation, its molecular function remains unknown (verdict kept 'dark'). |
Curated reference (UniProt)
| UniProt |
P95244
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BU0A |
|---|
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, 2 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxP (ESAT-6 like protein EsxP), medium confidence from genomic context alone (score 517 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) |
|---|---|---|---|---|
Rv2347c esxP |
ESAT-6 like protein EsxP | 597 | 517 ctx | neighborhood:494 |
Rv2352c PPE38 |
PPE family protein PPE38 | 751 | 514 | coexpression:514 textmining:510 |
Rv2349c plcC |
phospholipase C | 495 | 469 ctx | neighborhood:467 |
Rv2346c esxO |
ESAT-6 like protein EsxO | 491 | 430 ctx | neighborhood:403 |
Rv2350c plcB |
membrane-associated phospholipase B | 457 | 422 ctx | neighborhood:418 |
Rv2351c plcA |
membrane-associated phospholipase A | 475 | 258 | |
Rv3874 esxB |
ESAT-6-like protein EsxB | 433 | 85 | textmining:406 |
Rv3615c espC |
ESX-1 secretion-associated protein EspC | 497 | 82 | textmining:475 |
Rv3865 espF |
ESX-1 secretion-associated protein EspF | 449 | 63 | textmining:437 |
Rv2345 |
transmembrane protein | 804 | 47 | textmining:803 |
Rv2353c PPE39 |
PPE family protein PPE39 | 653 | 47 | textmining:651 |
Rv2248 hyp |
hypothetical protein | 547 | 44 | textmining:546 |
Rv0792c |
transcriptional regulator | 549 | 41 | textmining:549 |
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
- T-cell antigen; component of an ESAT-6-free IGRA with EspC/EspF (Ruhwald 2017, PMID 28387329)
- Variant I101M associated with human PRDM15 (genome-to-genome) (Xu 2025, PMID 40457403)
- Molecular function unknown - documented antigen context only
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216864.1)
- 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
2BU0A - Curated reference: UniProt P95244 (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 39.9, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
13 functional partner(s); context anchor
esxP - Primary literature: Ruhwald M, de Thurah L, Kuchaka D, Zaher MR, Salman AM, Abdel-Ghaffar AR, et al. (2017). Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6 Sci Rep 7:45969. doi:10.1038/srep45969 PMID:28387329
- Primary literature: Xu ZM, Zwyer M, Hiza H, Schmidiger S, Sasamalo M, Reinhard M, et al. (2025). Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania BMC Med Genomics 18(1):99. doi:10.1186/s12920-025-02164-x PMID:40457403
Ancestral MTBC0 protein sequence
>mtbc0_002500|Rv2348c| MLLPLGPPLPPDAVVAKRAESGMLGGLSVPLSWGVAVPPDDYDHWAPAPEDGADVDVQAAEGADAEAAAMDEWDEWQAWNEWVAENAEPRFEVPRSSSSVIPHSPAAG