mmcO Resolved · high auto-curated
H37Rv Rv0846c · MTBC0 mtbc0_000901 ·
504 aa · 945831–947345 (-) ·
RefSeq NP_215361.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidase |
|---|---|
| MTBC0 PGAP re-annotation | multicopper oxidase MmcO |
| Revised (this work) | Multicopper oxidase MmcO. Pfam: Cu-oxidase_3 (PF07732.22), Cu-oxidase (PF00394.29), Cu-oxidase_2 (PF07731.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6WZK7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Multicopper oxidase MmcO |
| EC (curated) |
EC 1.16.3.1
|
| Curated function | Required for copper resistance. In vitro, oxidizes organic substrates and Fe(2+). May act in vivo by oxidation of toxic periplasmic Cu(+). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mco |
| eggNOG description | PFAM multicopper oxidase |
| Orthologous group | COG2132 |
| Gene Ontology (7) |
GO:0005575, GO:0005623, GO:0030288, GO:0030313, GO:0031975, GO:0042597, GO:0044464
|
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 | 2.719 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.49% of strains (714) · 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 |
|---|---|---|---|---|
Cu-oxidase_3 | PF07732.22 | 6.5e-26 | 83–182 | Multicopper oxidase |
Cu-oxidase | PF00394.29 | 1.1e-23 | 190–347 | Multicopper oxidase |
Cu-oxidase_2 | PF07731.21 | 4.4e-29 | 389–500 | Multicopper oxidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpqS (lipoprotein LpqS), high confidence from genomic context alone (score 853 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1485 hemZ |
ferrochelatase | 925 | 914 | database:900 |
Rv1876 bfrA |
bacterioferritin BfrA | 919 | 911 | database:900 |
Rv0849 |
MFS-type transporter | 946 | 907 | coexpression:843 textmining:455 |
Rv3841 bfrB |
bacterioferritin BfrB | 918 | 906 | database:900 |
Rv0848 cysK2 |
cysteine synthase CysK | 951 | 901 | coexpression:846 textmining:534 |
Rv0850 |
Rv0850, (MTV043.43), len: 110 aa. Putative transposase (fragment), similar in part to others e.g. Q45144|Q4514 transposable element IS31831 | 919 | 863 | coexpression:800 textmining:433 |
Rv0847 lpqS |
lipoprotein LpqS | 980 | 853 ctx | neighborhood:772 textmining:870 |
Rv2963 |
integral membrane protein | 973 | 803 | coexpression:770 textmining:870 |
Rv3529c hyp |
hypothetical protein | 625 | 602 | database:592 |
Rv2267c stf3 hyp |
hypothetical protein | 624 | 601 | database:592 |
Rv0526 |
thioredoxin | 649 | 598 | coexpression:435 |
Rv1691 hyp |
hypothetical protein | 619 | 596 | database:592 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 587 | 579 | database:556 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA | 585 | 576 | database:556 |
Rv0435c |
ATPase | 585 | 576 | database:556 |
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: oxidase
- MTBC0 PGAP product: multicopper oxidase MmcO
- Pfam (hmmscan --cut_ga): Cu-oxidase_3 PF07732.22 (E=6e-26), Cu-oxidase PF00394.29 (E=1e-23), Cu-oxidase_2 PF07731.21 (E=4e-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_215361.1)
- Domains: Pfam-A via hmmscan --cut_ga — Cu-oxidase_3 (PF07732.22), Cu-oxidase (PF00394.29), Cu-oxidase_2 (PF07731.21)
- 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
COG2132 - Curated reference: UniProt I6WZK7 (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 —
60 functional partner(s); context anchor
lpqS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000901|Rv0846c|mmcO MPELATSGNAFDKRRFSRRGFLGAGIASGFALAACASKPTASGAAGMTAAIDAAEAARPHSGRTVTATLTPQPARIDLGGPIVSTLTYGNTIPGPLIRATVGDEIVVSVTNRLGDPTSVHWHGIALRNDMDGTEPATANIGPGGDFTYRFSVPDPGTYWAHPHVGLQGDHGLYLPVVVDDPTEPGHYDAEWIIILDDWTDGIGKSPQQLYGELTDPNKPTMQNTTGMPEGEGVDSNLLGGDGGDIAYPYYLINGRIPVAATSFKAKPGQRIRIRIINSAADTAFRIALAGHSMTVTHTDGYPVIPTEVDALLIGMAERYDVMVTAAGGVFPLVALAEGKNALARALLSTGAGSPPDPQFRPDELNWRVGTVEMFTAATTANLGRPEPTHDLPVTLGGTMAKYDWTINGEPYSTTNPLHVRLGQRPTLMFDNTTMMYHPIHLHGHTFQMIKADGSPGARKDTVIVLPKQKMRAVLVADNPGVWVMHCHNNYHQVAGMATRLDYIL