Rv3654c Family assigned · medium auto-curated
H37Rv Rv3654c · MTBC0 - ·
107 aa · 4094660–4094983 (-) ·
RefSeq NP_218171.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains Tad (PF13400.12) 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 |
O69622
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Apoptosis inhibitor Rv3654c |
| Curated function | Effector protein that participates in the suppression of macrophage apoptosis by blocking the extrinsic pathway. Recognizes the host polypyrimidine tract binding protein-associated splicing factor (PSF), which probably leads to its cleavage, diminishing the level of caspase-8 in macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | TIGRFAM helicase secretion neighborhood TadE-like protein |
| Orthologous group | 2DRBM |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Tad | PF13400.12 | 4.5e-08 | 1–43 | Putative Flp pilus-assembly TadE/G-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3659c (conjugal transfer protein), high confidence from genomic context alone (score 827 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) |
|---|---|---|---|---|
Rv3655c hyp |
hypothetical protein | 886 | 886 ctx | neighborhood:881 |
Rv3656c hyp |
hypothetical protein | 968 | 853 ctx | neighborhood:851 textmining:796 |
Rv3659c |
conjugal transfer protein | 964 | 827 ctx | neighborhood:824 textmining:803 |
Rv3658c |
transmembrane protein | 827 | 827 ctx | neighborhood:824 |
Rv3657c |
membrane protein | 962 | 824 ctx | neighborhood:813 textmining:796 |
Rv3660c ssd hyp |
hypothetical protein | 858 | 722 ctx | neighborhood:720 textmining:511 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 543 | 47 | textmining:541 |
Rv3364c hyp |
hypothetical protein | 659 | 45 | textmining:658 |
Rv1821 secA2 |
accessory Sec system translocase SecA2 | 433 | 45 | textmining:431 |
Rv3354 hyp |
hypothetical protein | 411 | 42 | textmining:411 |
Rv3236c |
integral membrane transport protein | 513 | 41 | textmining:513 |
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): Tad PF13400.12 (E=4e-08)
- (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_218171.2)
- Domains: Pfam-A via hmmscan --cut_ga — Tad (PF13400.12)
- 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
2DRBM - Curated reference: UniProt O69622 (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 —
11 functional partner(s); context anchor
Rv3659c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3654c| MLAVAMVAVLLCVTGAGAYLGSAVVARHRAQAAADLASLAAAARLPSGLAAACARATLVARAMRVEHAQCRVVDLDVVVTVEVAVAFAGVATATARAGPAKVPTTPG