mycP4 Resolved · high auto-curated
H37Rv Rv3449 · MTBC0 mtbc0_003668 ·
455 aa · 3895637–3897004 (+) ·
RefSeq NP_217966.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane-anchored mycosin |
|---|---|
| MTBC0 PGAP re-annotation | type VII secretion system ESX-4 serine protease mycosin MycP4 |
| Revised (this work) | Type VII secretion system ESX-4 serine protease mycosin MycP4. Pfam: Peptidase_S8 (PF00082.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YC58
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Mycosin-4 |
| EC (curated) |
EC 3.4.21.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | mycP4 |
| eggNOG description | Belongs to the peptidase S8 family |
| Orthologous group | COG1404 |
| KEGG orthology |
K14743
|
| Gene Ontology (2) |
GO:0005575, GO:0005576
|
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 | 0.256 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 4 missense, 2 nonsense, 0 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.83% of strains (1204) · 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 |
|---|---|---|---|---|
Peptidase_S8 | PF00082.28 | 9.8e-33 | 89–376 | Subtilase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccD4 (ESX-4 secretion system protein EccD4), high confidence from genomic context alone (score 987 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3448 eccD4 |
ESX-4 secretion system protein EccD4 | 995 | 987 ctx | neighborhood:882 coexpression:850 textmining:645 |
Rv3447c eccC4 |
ESX-4 secretion system protein EccC4 | 967 | 965 ctx | neighborhood:778 coexpression:807 |
Rv3446c hyp |
hypothetical protein | 962 | 960 ctx | neighborhood:708 coexpression:852 |
Rv0022c whiB5 |
transcriptional regulator WhiB5 | 801 | 801 | coexpression:801 |
Rv3444c esxT |
ESAT-6 like protein EsxT | 809 | 778 ctx | neighborhood:720 |
Rv3196 hyp |
hypothetical protein | 771 | 771 | coexpression:771 |
Rv3445c esxU |
ESAT-6 like protein EsxU | 900 | 766 ctx | neighborhood:733 textmining:592 |
Rv2488c |
LuxR family transcriptional regulator | 762 | 754 | coexpression:742 |
Rv3903c cpnT hyp |
hypothetical protein | 761 | 751 | coexpression:744 |
Rv0117 oxyS |
oxidative stress response regulatory protein OxyS | 755 | 745 | coexpression:744 |
Rv1190 hyp |
hypothetical protein | 740 | 737 | coexpression:735 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 745 | 736 | coexpression:736 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 745 | 736 | coexpression:735 |
Rv3082c virS |
HTH-type transcriptional regulator VirS | 737 | 736 | coexpression:731 |
Rv2891 hyp |
hypothetical protein | 744 | 735 | coexpression:735 |
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: membrane-anchored mycosin
- MTBC0 PGAP product: type VII secretion system ESX-4 serine protease mycosin MycP4
- Pfam (hmmscan --cut_ga): Peptidase_S8 PF00082.28 (E=1e-32)
- (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_217966.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S8 (PF00082.28)
- 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
COG1404 - Curated reference: UniProt I6YC58 (SwissProt, reviewed; Evidence at transcript 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 —
70 functional partner(s); context anchor
eccD4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003668|Rv3449|mycP4 MTTSRTLRLLVVSALATLSGLGTPVAHAVSPPPIDERWLPESALPAPPRPTVQREVCTEVTAESGRAFGRAERSAQLADLDQVWRLTRGAGQRVAVIDTGVARHRRLPKVVAGGDYVFTGDGTADCDAHGTLVAGIIAAAPDAQSDNFSGVAPDVTLISIRQSSSKFAPVGDPSSTGVGDVDTMAKAVRTAADLGASVINISSIACVPAAAAPDDRALGAALAYAVDVKNAVIVAAAGNTGGAAQCPPQAPGVTRDSVTVAVSPAWYDDYVLTVGSVNAQGEPSAFTLAGPWVDVAATGEAVTSLSPFGDGTVNRLGGQHGSIPISGTSYAAPVVSGLAALIRARFPTLTARQVMQRIESTAHHPPAGWDPLVGNGTVDALAAVSSDSIPQAGTATSDPAPVAVPVPRRSTPGPSDRRALHTAFAGAAICLLALMATLATASRRLRPGRNGIAGD