ripA Family assigned · medium auto-curated
H37Rv Rv1477 · MTBC0 mtbc0_001580 ·
472 aa · 1676795–1678213 (+) ·
RefSeq NP_215993.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | peptidoglycan endopeptidase RipA |
|---|---|
| MTBC0 PGAP re-annotation | NlpC/P60 family peptidoglycan endopeptidase RipA |
| Revised (this work) | NlpC/P60 family peptidoglycan endopeptidase RipA. Pfam: NLPC_P60 (PF00877.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53168
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptidoglycan endopeptidase RipA |
| EC (curated) |
EC 3.4.-.-
|
| Curated function | Peptidoglycan endopeptidase that cleaves the bond between D-glutamate and meso-diaminopimelate. Binds and degrades high-molecular weight peptidoglycan from a number of Actinobacteria; activity is increased in the presence of RpfB and inhibited by PBP1A (ponA1). Required for normal separation of daughter cells after cell division and for cell wall integrity. Required for host cell invasion and intracellular survival in host macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | rpfI |
| eggNOG description | NLP P60 protein |
| Orthologous group | COG0791 |
| KEGG orthology |
K21473, K21474
|
| Gene Ontology (16) |
GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0008150, GO:0008745, GO:0016787, GO:0016810, GO:0016811, GO:0030312 +4 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 | 0.137 · 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 |
|---|---|---|---|---|
NLPC_P60 | PF00877.26 | 2.9e-29 | 355–469 | NlpC/P60 family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ripB (peptidoglycan endopeptidase RipB), high confidence from genomic context alone (score 983 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1478 ripB |
peptidoglycan endopeptidase RipB | 984 | 983 ctx | neighborhood:874 coexpression:864 |
Rv3810 pirG |
cell surface protein | 843 | 843 | coexpression:801 |
Rv1566c ripD hyp |
hypothetical protein | 848 | 834 | coexpression:807 |
Rv2721c hyp |
hypothetical protein | 837 | 831 | coexpression:804 |
Rv0040c mtc28 hyp |
hypothetical protein | 810 | 800 | coexpression:800 |
Rv2154c ftsW |
lipid II flippase FtsW | 840 | 791 | coexpression:791 |
Rv0312 hyp |
hypothetical protein | 790 | 782 | coexpression:778 |
Rv1157c hyp |
hypothetical protein | 830 | 776 | coexpression:769 |
Rv3414c sigD |
ECF RNA polymerase sigma factor SigD | 774 | 774 | coexpression:770 |
Rv1497 lipL |
esterase LipL | 763 | 753 | coexpression:745 |
Rv1480 hyp |
hypothetical protein | 587 | 587 ctx | neighborhood:576 |
Rv1481 |
membrane protein | 805 | 585 ctx | neighborhood:566 textmining:549 |
Rv1158c hyp |
hypothetical protein | 580 | 580 | coexpression:580 |
Rv2525c hyp |
hypothetical protein | 604 | 576 | coexpression:562 |
Rv3102c ftsE |
cell division ATP-binding protein FtsE | 691 | 568 | coexpression:424 |
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: peptidoglycan endopeptidase RipA
- MTBC0 PGAP product: NlpC/P60 family peptidoglycan endopeptidase RipA
- Pfam (hmmscan --cut_ga): NLPC_P60 PF00877.26 (E=3e-29)
- (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_215993.1)
- Domains: Pfam-A via hmmscan --cut_ga — NLPC_P60 (PF00877.26)
- 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
COG0791 - Curated reference: UniProt O53168 (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
ripB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001580|Rv1477|ripA MRRNRRGSPARPAARFVRPAIPSALSVALLVCTPGLATADPQTDTIAALIADVAKANQRLQDLSDEVQAEQESVNKAMVDVETARDNAAAAEDDLEVSQRAVKDANAAIAAAQHRFDTFAAATYMNGPSVSYLSASSPDEIIATVTAAKTLSASSQAVMANLQRARTERVNTESAARLAKQKADKAAADAKASQDAAVAALTETRRKFDEQREEVQRLAAERDAAQARLQAARLVAWSSEGGQGAPPFRMWDPGSGPAGGRAWDGLWDPTLPMIPSANIPGDPIAVVNQVLGISATSAQVTANMGRKFLEQLGILQPTDTGITNAPAGSAQGRIPRVYGRQASEYVIRRGMSQIGVPYSWGGGNAAGPSKGIDSGAGTVGFDCSGLVLYSFAGVGIKLPHYSGSQYNLGRKIPSSQMRRGDVIFYGPNGSQHVTIYLGNGQMLEAPDVGLKVRVAPVRTAGMTPYVVRYIEY