marP Resolved · high auto-curated
H37Rv Rv3671c · MTBC0 mtbc0_003890 ·
397 aa · 4136152–4137345 (-) ·
RefSeq NP_218188.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine protease |
|---|---|
| MTBC0 PGAP re-annotation | acid resistance serine protease MarP |
| Revised (this work) | Acid resistance serine protease MarP. Pfam: Colicin_V (PF02674.23), Trypsin_2 (PF13365.13), Trypsin (PF00089.33). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHR9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine protease Rv3671c |
| EC (curated) |
EC 3.4.21.-
|
| Curated function | Required for M.tuberculosis resistance to oxidative stress in addition to its role in resistance to acid, which is essential for virulence. It protects M.tuberculosis against phagolysosomal concentrations of acid and maintains its intrabacterial pH when phagocytosed by IFN-gamma-activated macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | cvpA |
| eggNOG description | Colicin V production protein |
| Orthologous group | COG0265 |
| Gene Ontology (23) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0009268, GO:0009405, GO:0009628, GO:0010447, GO:0016020 +11 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 | 0.673 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 7 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 |
|---|---|---|---|---|
Colicin_V | PF02674.23 | 1.3e-13 | 7–149 | Colicin V production protein |
Trypsin_2 | PF13365.13 | 2.9e-27 | 220–357 | Trypsin-like peptidase domain |
Trypsin | PF00089.33 | 4.0e-12 | 221–363 | Trypsin |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nth (endonuclease III), high confidence from genomic context alone (score 793 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3672c hyp |
hypothetical protein | 930 | 929 ctx | neighborhood:816 database:530 |
Rv2115c mpa |
proteasome-associated ATPase | 824 | 813 | experimental:551 database:594 |
Rv3674c nth |
endonuclease III | 797 | 793 ctx | neighborhood:758 |
Rv0175 |
Mce associated membrane protein | 783 | 783 | coexpression:783 |
Rv3696c glpK |
glycerol kinase | 767 | 753 | experimental:402 database:589 |
Rv1334 mec |
[CysO | 708 | 698 | database:576 |
Rv3675 |
membrane protein | 742 | 697 ctx | neighborhood:697 |
Rv3673c |
membrane-anchored thioredoxin-like protein | 717 | 668 ctx | neighborhood:614 |
Rv3676 crp |
cAMP receptor protein | 691 | 665 ctx | neighborhood:655 |
Rv2109c prcA |
proteasome subunit alpha | 639 | 622 | database:562 |
Rv0415 thiO |
thiamine biosynthesis oxidoreductase ThiO | 627 | 622 | database:549 |
Rv1905c aao |
D-amino acid oxidase | 626 | 621 | database:549 |
Rv2110c prcB |
proteasome subunit beta | 700 | 620 | database:562 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 615 | 615 | database:556 |
Rv2555c alaS |
alanine--tRNA ligase | 626 | 614 | database:586 |
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: serine protease
- MTBC0 PGAP product: acid resistance serine protease MarP
- Pfam (hmmscan --cut_ga): Colicin_V PF02674.23 (E=1e-13), Trypsin_2 PF13365.13 (E=3e-27), Trypsin PF00089.33 (E=4e-12)
- (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_218188.1)
- Domains: Pfam-A via hmmscan --cut_ga — Colicin_V (PF02674.23), Trypsin_2 (PF13365.13), Trypsin (PF00089.33)
- 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
COG0265 - Curated reference: UniProt P9WHR9 (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 —
234 functional partner(s); context anchor
nth - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003890|Rv3671c|marP MTPSQWLDIAVLAVAFIAAISGWRAGALGSMLSFGGVLLGATAGVLLAPHIVSQISAPRAKLFAALFLILALVVVGEVAGVVLGRAVRGAIRNRPIRLIDSVIGVGVQLVVVLTAAWLLAMPLTQSKEQPELAAAVKGSRVLARVNEAAPTWLKTVPKRLSALLNTSGLPAVLEPFSRTPVIPVASPDPALVNNPVVAATEPSVVKIRSLAPRCQKVLEGTGFVISPDRVMTNAHVVAGSNNVTVYAGDKPFEATVVSYDPSVDVAILAVPHLPPPPLVFAAEPAKTGADVVVLGYPGGGNFTATPARIREAIRLSGPDIYGDPEPVTRDVYTIRADVEQGDSGGPLIDLNGQVLGVVFGAAVDDAETGFVLTAGEVAGQLAKIGATQPVGTGACVS