Rv1128c Family assigned · medium
H37Rv Rv1128c · MTBC0 - ·
451 aa · 1251617–1252972 (-) ·
RefSeq NP_215644.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | HNH-family endonuclease / nuclease (modification-dependent restriction-endonuclease or nuclease effector of a defense system); COG defense category V RefSeq leaves this locus uncharacterised. |
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 |
P9WM57
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized protein Rv1128c |
UniProt still lists this protein as Uncharacterized protein Rv1128c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | Domain of unknown function (DUF222) |
| Orthologous group | COG1403 |
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0030312, GO:0040007, GO:0044464, GO:0071944
|
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) pseudogene candidate
| pN/pS | 0.47 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 25.76% of strains (37410) · clonal |
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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 8.0e-119 | 37–360 | Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prpR (transcriptional regulator), medium confidence from genomic context alone (score 546 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) |
|---|---|---|---|---|
Rv0336 hyp |
hypothetical protein | 949 | 749 ctx | cooccurence:747 textmining:808 |
Rv0515 hyp |
hypothetical protein | 918 | 749 ctx | cooccurence:747 textmining:689 |
Rv3776 hyp |
hypothetical protein | 753 | 697 ctx | cooccurence:693 |
Rv2100 hyp |
hypothetical protein | 936 | 686 ctx | cooccurence:681 textmining:805 |
Rv1765c hyp |
hypothetical protein | 661 | 661 ctx | cooccurence:659 |
Rv2015c hyp |
hypothetical protein | 642 | 642 ctx | cooccurence:640 |
Rv3074 hyp |
hypothetical protein | 692 | 627 ctx | cooccurence:615 |
Rv1378c hyp |
hypothetical protein | 777 | 626 ctx | cooccurence:620 textmining:430 |
Rv1129c prpR |
transcriptional regulator | 549 | 546 ctx | neighborhood:534 |
Rv1303 hyp |
hypothetical protein | 536 | 536 ctx | cooccurence:536 |
Rv0756c hyp |
hypothetical protein | 506 | 506 ctx | cooccurence:502 |
Rv0185 hyp |
hypothetical protein | 455 | 455 ctx | cooccurence:431 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 448 | 448 ctx | neighborhood:440 |
Rv1125 hyp |
hypothetical protein | 445 | 446 ctx | cooccurence:444 |
Rv1126c hyp |
hypothetical protein | 445 | 445 ctx | neighborhood:438 |
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
- HHpred (significant): ~25 concordant hits all HNH endonucleases/restriction enzymes/defense nucleases 88-96% (HNH-MDRE 6YKF 95.8%, McrA 5mC-restriction, SAVED/CBASS effectors, CRISPR HNH Cas9/IscB); corroborated by eggNOG COG_cat V (defense)
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated function.
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_215644.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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
COG1403 - Curated reference: UniProt P9WM57 (SwissProt, reviewed; Inferred from homology)
- 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 —
24 functional partner(s); context anchor
prpR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1128c| MCSTREEITEAFASLATALSRVLGLTFDALTTPERLALLEHCETARRQLPSVEHTLINQIGEQSTEEELGGKLGLTLADRLRITRSEAKRRVAEAADLGQRRALTGEPLPPLLTATAKAQRHGLIGDGHVEVIRAFVHRLPSWVDLKTLEKAERDLAKQATQYRPDQLAKLAARIMDCLNPDGDYTDEDRARRRGLTLGKQDVDGMSRLSGYVTPELRATIEAVWAKLAAPGMCNPEQKAPCVNGAPSKEQARRDTRSCPQRNHDALNAELRSLLTSGNLGQHNGLPASIIVTTTLKDLEAAAGAGLTGGGTILPISDVIRLARHANHYLAIFDRGKALALYHTKRLASPAQRIMLYAKDSGCSAPGCDVPGYYCEVHHVTPYAQCRNTDVNDLTLGCGGHHPLAERGWTTRKNAHGDTEWLPPPHLDHGQPRVNTFHHPEKLLADDEGDP