mce3B Family assigned · medium auto-curated
H37Rv Rv1967 · MTBC0 mtbc0_002083 ·
342 aa · 2229718–2230746 (+) ·
RefSeq NP_216483.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce3B |
|---|---|
| MTBC0 PGAP re-annotation | virulence factor Mce family protein |
| Revised (this work) | Virulence factor Mce 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 |
O53968
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Mce-family protein Mce3B |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce3B |
| eggNOG description | Virulence factor Mce family 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 | 0.732 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 8 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 |
|---|---|---|---|---|
MlaD | PF02470.26 | 1.6e-19 | 38–114 | MlaD protein |
Mce4_CUP1 | PF11887.14 | 9.5e-29 | 120–333 | Cholesterol uptake porter CUP1 of Mce4, putative |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: yrbE3B (integral membrane protein), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1965 yrbE3B |
integral membrane protein | 996 | 996 ctx | neighborhood:785 cooccurence:773 coexpression:881 |
Rv1964 yrbE3A |
integral membrane protein | 995 | 995 ctx | neighborhood:785 cooccurence:767 coexpression:863 |
Rv1971 mce3F |
Mce family protein Mce3F | 996 | 993 ctx | neighborhood:795 cooccurence:774 coexpression:860 textmining:566 |
Rv1966 mce3A |
Mce family protein Mce3A | 997 | 992 ctx | neighborhood:781 cooccurence:772 coexpression:860 textmining:673 |
Rv1970 lprM |
Mce family lipoprotein LprM | 995 | 992 ctx | neighborhood:781 cooccurence:774 coexpression:860 textmining:464 |
Rv1972 |
Mce associated membrane protein | 984 | 985 ctx | neighborhood:729 cooccurence:712 coexpression:822 |
Rv1968 mce3C |
Mce family protein Mce3C | 986 | 979 ctx | neighborhood:795 coexpression:860 |
Rv1969 mce3D |
Mce family protein Mce3D | 983 | 977 ctx | neighborhood:781 coexpression:860 |
Rv1973 |
Mce associated membrane protein | 960 | 961 ctx | neighborhood:714 cooccurence:502 coexpression:746 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 890 | 885 ctx | cooccurence:764 experimental:431 |
Rv0588 yrbE2B hyp |
hypothetical protein | 881 | 878 ctx | cooccurence:771 |
Rv0168 yrbE1B |
membrane protein | 910 | 874 ctx | cooccurence:771 |
Rv0587 yrbE2A hyp |
hypothetical protein | 876 | 872 ctx | cooccurence:766 |
Rv3500c yrbE4B |
integral membrane protein | 876 | 872 ctx | cooccurence:772 |
Rv0167 yrbE1A |
membrane protein | 902 | 870 ctx | cooccurence:768 |
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 Mce3B
- MTBC0 PGAP product: virulence factor Mce family protein
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=2e-19), Mce4_CUP1 PF11887.14 (E=1e-28)
- (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_216483.1)
- 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 O53968 (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 —
42 functional partner(s); context anchor
yrbE3B - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002083|Rv1967|mce3B MRENLGGVVVRLGVFLAVCLLTAFLLIAVFGEVRFGDGKTYYAEFANVSNLRTGKLVRIAGVEVGKVTRISINPDATVRVQFTADNSVTLTRGTRAVIRYDNLFGDRYLALEEGAGGLAVLRPGHTIPLARTQPALDLDALIGGFKPLFRALNPEQVNALSEQLLHAFAGQGPTIGSLLAQSAAVTNTLADRDRLIGQVITNLNVVLGSLGAHTDRLDQAVTSLSALIHRLAQRKTDISNAVAYTNAAAGSVADLLSQARAPLAKVVRETDRVAGIAAADHDYLDNLLNTLPDKYQALVRQGMYGDFFAFYLCDVVLKVNGKGGQPVYIKLAGQDSGRCAPK