Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | DUF3060 domain-containing protein |
| Revised (this work) | Membrane protein (16.6 kDa) of the cell envelope implicated in host-cell invasion; a dimorphic antigen carrying a Beijing-genotype-specific Asn142Lys polymorphism with distinct antibody responses. Rv0679c-derived peptides bind A549/U937 cells and TLR2/TLR4 and inhibit bacillary entry, suggesting a role in invasion (Zhao 2017). Molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
I6WZ30
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | Conserved threonine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
| eggNOG description | Protein of unknown function (DUF3060) |
| Orthologous group | 295VX |
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 |
0.56 · relaxed/neutral
|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 3 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 |
DUF3060 | PF11259.14 |
9.1e-22 | 101–159 |
Protein of unknown function (DUF3060) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv0680c (transmembrane protein),
high confidence from genomic context alone
(score 970 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) |
Rv0680c |
transmembrane protein |
970 |
970 ctx |
neighborhood:882 coexpression:759 |
Rv0681 |
transcriptional regulator |
688 |
688 ctx |
neighborhood:679 |
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
- Membrane protein; invasion-inhibiting binding peptides; dimorphic Beijing N142K antigen (Zhao 2017, PMID 28506215)
- 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_215193.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3060 (PF11259.14)
- 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
295VX
- Curated reference: UniProt
I6WZ30
(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 88.3, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
2 functional partner(s); context anchor
Rv0680c
- Primary literature: Zhao J, Matsuba T, Zhang X, Leano S, Nakajima C, Chagan-Yasutan H, Telan EF, Suzuki Y, Hattori T (2017). Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study BMC Infect Dis 17(1):344.
doi:10.1186/s12879-017-2442-5 PMID:28506215
Ancestral MTBC0 protein sequence
>mtbc0_000718|Rv0679c|
MVEKPLRADRATHSRLATFALALAAAALPLAGCSSTANPPAATTTPATATTTTATSGPTAAPTVTTGESTTASIQIGDMLTYGSIGTTATLDCADGKSLNVAGSDNTLTVNGTCETVTVGGANNKIAFDRIDERLVVVGLDNTVTYKNGDPTIDNLGAGNRINKE
Spot an error? Suggest an improvement