rip Resolved · high auto-curated
H37Rv Rv2869c · MTBC0 mtbc0_003051 ·
404 aa · 3201214–3202428 (-) ·
RefSeq NP_217385.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | zinc metalloprotease |
|---|---|
| MTBC0 PGAP re-annotation | zinc metalloprotease Rip |
| Revised (this work) | Zinc metalloprotease Rip. Pfam: Peptidase_M50 (PF02163.29), PDZ_6 (PF17820.8). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHS3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Zinc metalloprotease Rip1 |
| EC (curated) |
EC 3.4.24.-
|
| Curated function | A probable intramembrane site-2 protease (S2P) that cleaves type-2 transmembrane proteins within their membrane-spanning domains. Cleaves PbpB (PBP3, FtsI) near 'Ala-102' and 'Ala-103' in response to oxidative stress; cleavage is inhibited by Wag31-PbpB interaction. Probably also cleaves anti-sigma factors RskA, RslA and RsmA but not RsdA..; FUNCTION: Regulated intramembrane proteolysis (RIP) occurs when an extracytoplasmic signal (possibly oxidative stress) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The membrane-spanning regulatory substrat. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | rip1 |
| eggNOG description | peptidase |
| Orthologous group | COG0750 |
| KEGG orthology |
K11749
|
| KEGG pathways |
map02024, map04112
|
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
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 | 0.706 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 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 |
|---|---|---|---|---|
Peptidase_M50 | PF02163.29 | 3.3e-55 | 10–374 | Peptidase family M50 |
PDZ_6 | PF17820.8 | 2.3e-08 | 157–201 | PDZ domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dxr (1-deoxy-D-xylulose 5-phosphate reductoisomerase), high confidence from genomic context alone (score 934 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 953 | 934 ctx | neighborhood:882 coexpression:464 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 816 | 817 ctx | neighborhood:808 |
Rv2867c |
GCN5-like N-acetyltransferase | 805 | 804 ctx | neighborhood:795 |
Rv2881c cdsA |
phosphatidate cytidylyltransferase | 700 | 699 | coexpression:648 |
Rv2873 mpt83 |
cell surface lipoprotein | 692 | 693 ctx | neighborhood:693 |
Rv2361c uppS |
decaprenyl diphosphate synthase | 665 | 651 | coexpression:603 |
Rv3859c gltB |
glutamate synthase large subunit | 817 | 630 ctx | neighborhood:544 textmining:527 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase | 637 | 622 | coexpression:608 |
Rv1087A |
Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT | 632 | 617 | coexpression:602 |
Rv2903c lepB |
signal peptidase | 610 | 574 | coexpression:412 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 584 | 557 | coexpression:458 |
Rv2864c |
penicillin-binding lipoprotein | 579 | 554 ctx | neighborhood:528 |
Rv2871 vapB43 |
antitoxin VapB43 | 549 | 549 ctx | neighborhood:549 |
Rv2872 vapC43 |
ribonuclease VapC43 | 542 | 542 ctx | neighborhood:542 |
Rv2158c murE |
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase | 552 | 535 ctx | cooccurence:507 |
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: zinc metalloprotease
- MTBC0 PGAP product: zinc metalloprotease Rip
- Pfam (hmmscan --cut_ga): Peptidase_M50 PF02163.29 (E=3e-55), PDZ_6 PF17820.8 (E=2e-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_217385.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M50 (PF02163.29), PDZ_6 (PF17820.8)
- 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
COG0750 - Curated reference: UniProt P9WHS3 (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 —
64 functional partner(s); context anchor
dxr - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003051|Rv2869c|rip MMFVTGIVLFALAILISVALHECGHMWVARRTGMKVRRYFVGFGPTLWSTRRGETEYGVKAVPLGGFCDIAGMTPVEELDPDERDRAMYKQATWKRVAVLFAGPGMNLAICLVLIYAIALVWGLPNLHPPTRAVIGETGCVAQEVSQGKLEQCTGPGPAALAGIRSGDVVVKVGDTPVSSFDEMAAAVRKSHGSVPIVVERDGTAIVTYVDIESTQRWIPNGQGGELQPATVGAIGVGAARVGPVRYGVFSAMPATFAFTGDLTVEVGKALAALPTKVGALVRAIGGGQRDPQTPISVVGASIIGGDTVDHGLWVAFWFFLAQLNLILAAINLLPLLPFDGGHIAVAVFERIRNMVRSARGKVAAAPVNYLKLLPATYVVLVLVVGYMLLTVTADLVNPIRLFQ