Rv2645 Still unknown · low
H37Rv Rv2645 · MTBC0 mtbc0_002820 ·
143 aa · 2993684–2994115 (+) ·
RefSeq NP_217161.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Immunodominant T-cell antigen encoded in region-of-difference RD13 (present in M. tuberculosis, absent from BCG and M. bovis); a cell-mediated-immunity-based diagnostic/vaccine antigen. Despite this immunological characterisation, its molecular/biochemical function remains unknown (verdict kept 'dark'). |
Curated reference (UniProt)
| UniProt |
P9WL51
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2645 |
UniProt still lists this protein as Uncharacterized protein Rv2645; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.353 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2646 (integrase), high confidence from genomic context alone (score 953 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) |
|---|---|---|---|---|
Rv2646 |
integrase | 952 | 953 ctx | neighborhood:774 coexpression:799 |
Rv2647 hyp |
hypothetical protein | 553 | 553 ctx | neighborhood:529 |
Rv2661c hyp |
hypothetical protein | 871 | 55 | textmining:870 |
Rv1573 |
phage protein | 630 | 55 | textmining:625 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 804 | 47 | textmining:803 |
Rv2738c hyp |
hypothetical protein | 810 | 46 | textmining:810 |
Rv0310c hyp |
hypothetical protein | 808 | 46 | textmining:807 |
Rv2290 lppO |
lipoprotein LppO | 652 | 46 | textmining:651 |
Rv1255c |
HTH-type transcriptional regulator | 803 | 45 | textmining:803 |
Rv2650c |
prophage protein | 816 | 44 | textmining:816 |
Rv2659c |
prophage integrase | 660 | 44 | textmining:659 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 654 | 44 | textmining:653 |
Rv2291 sseB |
thiosulfate sulfurtransferase SseB | 631 | 44 | textmining:630 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 660 | 42 | textmining:660 |
Rv3669 |
transmembrane protein | 816 | 41 | textmining:816 |
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
- RD13 immunodominant T-cell antigen; M.tb-specific; CMI diagnostic agent (Luo 2015, PMID 26318635)
- BCG::Rv2645 enhances protective immunity (Luo 2018, PMID 29681409)
- 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_217161.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt P9WL51 (SwissProt, reviewed; 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)
- 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
Rv2646 - Primary literature: Luo W, Qu ZL, Xie Y, Xiang J, Zhang XL (2015). Identification of a novel immunodominant antigen Rv2645 from RD13 with potential as a cell-mediated immunity-based TB diagnostic agent J Infect 71(5):534-43. doi:10.1016/j.jinf.2015.07.011 PMID:26318635
- Primary literature: Luo W, Qu Z, Zhang L, Xie Y, Luo F, Tan Y, Pan Q, Zhang XL (2018). Recombinant BCG::Rv2645 elicits enhanced protective immunity compared to BCG in vivo with induced ISGylation-related genes and Th1 and Th17 responses Vaccine 36(21):2998-3009. doi:10.1016/j.vaccine.2018.04.025 PMID:29681409
Ancestral MTBC0 protein sequence
>mtbc0_002820|Rv2645| MTTTPRQPLFCAHADTNGDPGRCACGQQLADVGPATPPPPWCEPGTEPIWEQLTERYGGVTICQWTRYFPAGDPVAADVWIAADDRVVDGRVLRTQPAIHYTEPPVLGIGPAAARRLAAELLNAADTLDDGRRQLDDLGEHRR