Rv2018 Family assigned · medium auto-curated
H37Rv Rv2018 · MTBC0 mtbc0_002148 ·
239 aa · 2288893–2289612 (+) ·
RefSeq NP_216534.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF433 domain-containing protein |
| Revised (this work) | DUF433 domain-containing protein. Pfam: HTH_66 (PF21321.4), DUF433 (PF04255.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53464
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative antitoxin VapB45 |
| Curated function | Possibly the antitoxin component of a type II toxin-antitoxin (TA) system. Its cognate toxin is VapC45. |
UniProt still lists this protein as Putative antitoxin VapB45; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF433) |
| Orthologous group | COG2442 |
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 | 0.139 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HTH_66 | PF21321.4 | 9.5e-31 | 14–96 | Putative DNA-binding HTH domain |
DUF433 | PF04255.21 | 3.9e-10 | 183–234 | Protein of unknown function (DUF433) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB49 (antitoxin VapB45), medium confidence from genomic context alone (score 552 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) |
|---|---|---|---|---|
Rv2019 vapC45 hyp |
hypothetical protein | 890 | 803 ctx | neighborhood:802 textmining:464 |
Rv3181c vapB49 |
antitoxin VapB45 | 785 | 552 ctx | cooccurence:551 textmining:540 |
Rv0582 vapC26 |
ribonuclease VapC26 | 546 | 547 ctx | cooccurence:545 |
Rv0960 vapC9 |
ribonuclease VapC9 | 534 | 523 ctx | cooccurence:522 |
Rv2231A vapC16 |
ribonuclease VapC16 | 517 | 516 ctx | cooccurence:516 |
Rv0617 vapC29 |
ribonuclease VapC29 | 505 | 506 ctx | cooccurence:502 |
Rv3320c vapC44 |
ribonuclease VapC44 | 502 | 502 ctx | cooccurence:500 |
Rv2494 vapC38 |
ribonuclease VapC38 | 510 | 497 ctx | cooccurence:492 |
Rv2735c hyp |
hypothetical protein | 488 | 489 ctx | cooccurence:488 |
Rv3098A |
PemK-like protein | 488 | 488 ctx | cooccurence:488 |
Rv2530c vapC39 |
ribonuclease VapC39 | 482 | 482 ctx | cooccurence:480 |
Rv2016 hyp |
hypothetical protein | 470 | 470 ctx | neighborhood:443 |
Rv2017 |
transcriptional regulator | 688 | 469 ctx | neighborhood:456 textmining:438 |
Rv1004c |
membrane protein | 466 | 467 ctx | cooccurence:464 |
Rv0304c PPE5 |
PPE family protein PPE5 | 459 | 460 ctx | cooccurence:457 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: DUF433 domain-containing protein
- Pfam (hmmscan --cut_ga): HTH_66 PF21321.4 (E=1e-30), DUF433 PF04255.21 (E=4e-10)
- (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_216534.1)
- Domains: Pfam-A via hmmscan --cut_ga — HTH_66 (PF21321.4), DUF433 (PF04255.21)
- 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
COG2442 - Curated reference: UniProt O53464 (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 —
49 functional partner(s); context anchor
vapB49 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002148|Rv2018| MAGDQELELRFDVPLYTLAEASRYLVVPRATLATWADGYERRPANAPAVQGQPIITALPHPTGSHARLPFVGIAEAYVLNAFRRAGVPMQRIRPSLDWLIKNVGPHALASQDLCTDGAEVLWRFAERSGEGSPDDLVVRGLIVPRSGQYVFKEIVEHYLQQISFADDNLASMIRLPQYGDANVVLDPRRGYGQPVFDGSGVRVADVLGPLRAGATFQAVADDYGVTPDQLRDALDAIAA