mce3A Family assigned · medium auto-curated
H37Rv Rv1966 · MTBC0 - ·
425 aa · 2209327–2210604 (+) ·
RefSeq YP_177852.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce3A |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Mce family protein Mce3A. 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
L7N698
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Mce-family protein Mce3A |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce3A |
| 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 | 2.106 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 | 2.7e-15 | 41–120 | MlaD protein |
Mce4_CUP1 | PF11887.14 | 8.9e-80 | 127–346 | 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 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1965 yrbE3B |
integral membrane protein | 998 | 995 ctx | neighborhood:785 cooccurence:757 coexpression:881 textmining:659 |
Rv1964 yrbE3A |
integral membrane protein | 997 | 994 ctx | neighborhood:782 cooccurence:690 coexpression:878 textmining:602 |
Rv1970 lprM |
Mce family lipoprotein LprM | 998 | 993 ctx | neighborhood:783 cooccurence:774 coexpression:860 textmining:824 |
Rv1968 mce3C |
Mce family protein Mce3C | 997 | 993 ctx | neighborhood:787 cooccurence:774 coexpression:860 textmining:687 |
Rv1969 mce3D |
Mce family protein Mce3D | 997 | 993 ctx | neighborhood:784 cooccurence:774 coexpression:859 textmining:687 |
Rv1971 mce3F |
Mce family protein Mce3F | 995 | 993 ctx | neighborhood:787 cooccurence:774 coexpression:860 textmining:443 |
Rv1967 mce3B |
Mce family protein Mce3B | 997 | 992 ctx | neighborhood:781 cooccurence:772 coexpression:860 textmining:673 |
Rv1972 |
Mce associated membrane protein | 993 | 987 ctx | neighborhood:714 cooccurence:767 coexpression:820 textmining:547 |
Rv1973 |
Mce associated membrane protein | 986 | 982 ctx | neighborhood:715 cooccurence:737 coexpression:785 |
Rv1974 |
membrane protein | 946 | 856 ctx | neighborhood:691 coexpression:553 textmining:644 |
Rv0168 yrbE1B |
membrane protein | 903 | 854 ctx | cooccurence:736 |
Rv3500c yrbE4B |
integral membrane protein | 866 | 854 ctx | cooccurence:740 |
Rv0588 yrbE2B hyp |
hypothetical protein | 889 | 853 ctx | cooccurence:732 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 895 | 847 ctx | cooccurence:684 experimental:431 |
Rv3501c yrbE4A |
integral membrane protein | 844 | 841 ctx | cooccurence:710 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): Mce family protein Mce3A
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=3e-15), Mce4_CUP1 PF11887.14 (E=9e-80)
- (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 YP_177852.1)
- 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 L7N698 (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 —
58 functional partner(s); context anchor
yrbE3B - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1966|mce3A MRRGPGRHRLHDAWWTLILFAVIGVAVLVTAVSFTGSLRSTVPVTLAADRSGLVMDSGAKVMMRGVQVGRVAQIGRIEWAQNGASLRLEIDPDQIRYIPANVEAQISATTAFGAKFVDLVMPQNPSRARLSAGAVLHSKNVSTEINTVFENVVDLLNMIDPLKLNAVLTAVADAVRGQGERIGQATTDLNEVLEALNARGDTIGGNWRSLKNFTDTYDAAAQDILTILNAASTTSATVVNHSTQLDALLLNAIGLSNAGTNLLGSSRDNLVGAADILAPTTSLLFKYNPEYTCFLQGAKWYLDNGGYAAWGGADGRTLQLDVALLFGNDPYVYPDNLPVVAAKGGPGGRPGCGPLPDATHNFPVRQLVTNTGWGTGLDIRPNPGIGHPCWANYFPVTRAVPEPPSIRQCIPGPAIGPNPAAGEQP