Rv3655c Resolved · medium auto-curated
H37Rv Rv3655c · MTBC0 mtbc0_003873 ·
99 aa · 4118754–4119130 (-) ·
RefSeq NP_218172.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | apoptosis inhibitor |
| Revised (this work) | Apoptosis inhibitor. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69623
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Apoptosis inhibitor Rv3655c |
| Curated function | Effector protein that participates in the suppression of macrophage apoptosis by blocking the extrinsic pathway. Interferes with caspase-8 activation and binds to the host E3 ubiquitin-protein ligase RNF213, whose fusion partners have anti-apoptotic function. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2EGB2 |
|---|---|
| Gene Ontology (28) |
GO:0008150, GO:0010941, GO:0033668, GO:0035821, GO:0042981, GO:0043067, GO:0043069, GO:0044003, GO:0044068, GO:0044403, GO:0044419, GO:0044531 +16 more
|
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 | 0.1 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 95.96% of strains (139346) · reference-fixed |
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: Rv3658c (transmembrane protein), high confidence from genomic context alone (score 912 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) |
|---|---|---|---|---|
Rv3658c |
transmembrane protein | 921 | 912 ctx | neighborhood:793 coexpression:593 |
Rv3656c hyp |
hypothetical protein | 900 | 900 ctx | neighborhood:851 |
Rv3659c |
conjugal transfer protein | 903 | 897 ctx | neighborhood:795 coexpression:516 |
Rv3654c hyp |
hypothetical protein | 886 | 886 ctx | neighborhood:881 |
Rv3657c |
membrane protein | 889 | 877 ctx | neighborhood:741 coexpression:545 |
Rv1364c |
sigma factor regulatory protein | 809 | 809 | coexpression:806 |
Rv0990c hyp |
hypothetical protein | 751 | 728 | coexpression:706 |
Rv0412c glnX |
membrane protein | 570 | 570 ctx | cooccurence:570 |
Rv2446c |
integral membrane protein | 542 | 542 ctx | cooccurence:541 |
Rv3660c ssd hyp |
hypothetical protein | 540 | 528 ctx | neighborhood:521 |
Rv0948c |
chorismate mutase | 503 | 504 ctx | cooccurence:499 |
Rv0358 hyp |
hypothetical protein | 500 | 501 ctx | cooccurence:493 |
Rv1382 hyp |
hypothetical protein | 475 | 476 ctx | cooccurence:474 |
Rv1354c hyp |
hypothetical protein | 496 | 464 | coexpression:455 |
Rv1083 hyp |
hypothetical protein | 461 | 461 ctx | cooccurence:461 |
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: apoptosis inhibitor
- (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_218172.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
2EGB2 - Curated reference: UniProt O69623 (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 —
25 functional partner(s); context anchor
Rv3658c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003873|Rv3655c| MEAALAIATLVLVLVLCLAGVTAVSMQVRCIDAAREAARLAARGDVRSATDVARSIAPRAALVQVHRDGEFVVATVTAHSNLLPTLDIAARAISVAEPG