mce2F Family assigned · medium auto-curated
H37Rv Rv0594 · MTBC0 mtbc0_000624 ·
516 aa · 696789–698339 (+) ·
RefSeq NP_215108.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce2F |
|---|---|
| MTBC0 PGAP re-annotation | MlaD family protein |
| Revised (this work) | MlaD family protein. Pfam: MlaD (PF02470.26), Mce4_CUP1 (PF11887.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07784
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Mce-family protein Mce2F |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce2F |
| eggNOG description | MlaD protein |
| Orthologous group | COG1463 |
| KEGG orthology |
K02067
|
| KEGG pathways |
map02010
|
| KEGG modules |
M00210, M00669, M00670
|
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 | 1.061 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 8 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (247) · 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 |
|---|---|---|---|---|
MlaD | PF02470.26 | 6.3e-17 | 39–112 | MlaD protein |
Mce4_CUP1 | PF11887.14 | 1.7e-08 | 125–284 | Cholesterol uptake porter CUP1 of Mce4, putative |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lprL (Mce family lipoprotein LprL), high confidence from genomic context alone (score 956 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0588 yrbE2B hyp |
hypothetical protein | 984 | 969 ctx | neighborhood:781 cooccurence:764 textmining:529 |
Rv0587 yrbE2A hyp |
hypothetical protein | 991 | 967 ctx | neighborhood:785 cooccurence:751 textmining:734 |
Rv0593 lprL |
Mce family lipoprotein LprL | 992 | 956 ctx | neighborhood:801 cooccurence:774 textmining:830 |
Rv0589 mce2A |
Mce family protein Mce2A | 982 | 948 ctx | neighborhood:780 cooccurence:774 textmining:674 |
Rv0590 mce2B |
Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( | 950 | 947 ctx | neighborhood:781 cooccurence:768 |
Rv3500c yrbE4B |
integral membrane protein | 873 | 869 ctx | cooccurence:766 |
Rv3501c yrbE4A |
integral membrane protein | 883 | 867 ctx | cooccurence:757 |
Rv0168 yrbE1B |
membrane protein | 872 | 867 ctx | cooccurence:764 |
Rv0592 mce2D |
Mce family protein Mce2D | 906 | 866 ctx | neighborhood:781 |
Rv0167 yrbE1A |
membrane protein | 882 | 865 ctx | cooccurence:755 |
Rv1965 yrbE3B |
integral membrane protein | 869 | 864 ctx | cooccurence:758 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 868 | 863 ctx | cooccurence:723 experimental:431 |
Rv0591 mce2C |
Mce family protein Mce2C | 912 | 853 ctx | neighborhood:785 textmining:426 |
Rv1964 yrbE3A |
integral membrane protein | 855 | 853 ctx | cooccurence:742 |
Rv0590A |
Mce-family related protein; Rv0590A, len: 84 aa. Probable continuation of mce2B|Rv0590. Can find no frameshift to account for this. Possible | 797 | 784 ctx | neighborhood:781 |
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: Mce family protein Mce2F
- MTBC0 PGAP product: MlaD family protein
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=6e-17), Mce4_CUP1 PF11887.14 (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_215108.1)
- Domains: Pfam-A via hmmscan --cut_ga — MlaD (PF02470.26), Mce4_CUP1 (PF11887.14)
- 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
COG1463 - Curated reference: UniProt O07784 (TrEMBL, unreviewed; Predicted)
- 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 —
57 functional partner(s); context anchor
lprL - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000624|Rv0594|mce2F MLTRAIKTQLVLLTVLAVIAVVVLGWYFLRIPSLVGIGRYTLYAELPRSGGLYRTANVTYRGITIGKVTGVEPTERGARATMSIDNGYQIPTDASANVHSVSAVGEQFVDLVSTRTSGPYLRHGQTITTTTVPSQIGPALDAANRGLAVLPKDRVASVLHEASEAVGGLGSSLNRLIEATQAIAHDVRGSLEDIDDIIERSAPIIDSQVNSGNEIARWAANLNTLAAQTAQTDPAVRSILANAAPTADQVNATFSDVRESLPQTLANLEVVIDMLKRYHNGVEQALVFLPQSGAIAQSVTTEFPGQAGLGVGGLALNQPPPCLTGFLPASEWRSPADTSTAPLPKGTYCRIPMDASNVVRGARNNPCVDVPGKRAATPRECRSNEAYVPGGTNPWYGDPNQMLSCPAPAARCDQPVKPGQVIPAPSVNNGINPLPADQLPGTPPPVNDPLQRPGSGTVQCNGQQPNPCVYTPSTFPTTIYDVQSGKVVAPDGVVYSVEASTHAGADGWKVMLAPTG