Rv2008c Family assigned · medium auto-curated
H37Rv Rv2008c · MTBC0 - ·
441 aa · 2256617–2257942 (-) ·
RefSeq NP_216524.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains AAA_14 (PF13173.13), DUF4143 (PF13635.13) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
P9WLM9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2008c |
UniProt still lists this protein as Uncharacterized protein Rv2008c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4143) |
| Orthologous group | COG1373 |
| KEGG orthology |
K07133
|
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 | 0.268 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
AAA_14 | PF13173.13 | 4.6e-18 | 72–187 | AAA domain |
DUF4143 | PF13635.13 | 1.3e-44 | 227–381 | Domain of unknown function (DUF4143) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapC15 (ribonuclease VapC15), high confidence from genomic context alone (score 724 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) |
|---|---|---|---|---|
Rv2010 vapC15 |
ribonuclease VapC15 | 723 | 724 ctx | neighborhood:600 |
Rv2009 vapB15 |
antitoxin VapB15 | 600 | 600 ctx | neighborhood:600 |
Rv2007c fdxA |
ferredoxin | 455 | 455 ctx | neighborhood:452 |
Rv0919 |
GCN5-like N-acetyltransferase | 433 | 434 ctx | cooccurence:430 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): AAA_14 PF13173.13 (E=5e-18), DUF4143 PF13635.13 (E=1e-44)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_216524.1)
- Domains: Pfam-A via hmmscan --cut_ga — AAA_14 (PF13173.13), DUF4143 (PF13635.13)
- 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
COG1373 - Curated reference: UniProt P9WLM9 (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 —
4 functional partner(s); context anchor
vapC15 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2008c| MDEIESLIGLRPTPLTWPVVIAGDFLGVWDPPPSLPGAANHEISAPTARISCMLIERRDAAARLRRALHRAPVVLLTGPRQAGKTTLSRLVGKSAPECTFDAENPVDATRLADPMLALSGLSGLITIDEAQRIPDLFPVLRVLVDRPVMPARFLILGSASPDLVGLASESLAGRVELVELSGLTVRDVGSSAADRLWLRGGLPPSFTARSNEDSAAWRDGYITTFLERDLAQLGVRIPAATMRRAWTMLAHYHGQLFSGAELARSLDVAQTTARRYLDALTDALVVRQLTPWFANIGKRQRRSPKIYIRDTGLLHRLLGIDDRLALERNPKLGASWEGFVLEQLAALLAPNPLYYWRTQQDAELDLYVELSGRPYGFEIKRTSTPSISRSMRSALVDLQLARLAIVYPGEHRFPLSDTVVAVPADQILTTGSVDELLALLK