mce4F Family assigned · medium auto-curated
H37Rv Rv3494c · MTBC0 mtbc0_003709 ·
564 aa · 3936257–3937951 (-) ·
RefSeq NP_218011.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce4 |
|---|---|
| MTBC0 PGAP re-annotation | virulence factor Mce family protein |
| Revised (this work) | Virulence factor Mce family protein. Pfam: MlaD (PF02470.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YC95
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mce-family protein Mce4F |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce4F |
| 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 | 1.073 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 | 5.4e-19 | 39–114 | MlaD protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mce4D (Mce family protein Mce4D), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3496c mce4D |
Mce family protein Mce4D | 998 | 994 ctx | neighborhood:879 cooccurence:769 coexpression:806 textmining:833 |
Rv3497c mce4C |
Mce family protein Mce4C | 999 | 993 ctx | neighborhood:879 cooccurence:766 coexpression:770 textmining:887 |
Rv3495c lprN |
Mce family lipoprotein LprN | 994 | 992 ctx | neighborhood:879 cooccurence:766 coexpression:730 |
Rv3498c mce4B |
Mce family protein Mce4B | 997 | 977 ctx | neighborhood:879 cooccurence:761 textmining:882 |
Rv3500c yrbE4B |
integral membrane protein | 995 | 977 ctx | neighborhood:856 cooccurence:736 textmining:815 |
Rv3492c |
Mce associated protein | 974 | 974 ctx | neighborhood:881 cooccurence:723 |
Rv3501c yrbE4A |
integral membrane protein | 993 | 967 ctx | neighborhood:813 cooccurence:704 textmining:807 |
Rv3499c mce4A |
Mce family protein Mce4A | 960 | 918 ctx | neighborhood:879 textmining:540 |
Rv3493c |
Mce associated protein | 905 | 905 ctx | neighborhood:881 |
Rv1965 yrbE3B |
integral membrane protein | 857 | 852 ctx | cooccurence:732 |
Rv0168 yrbE1B |
membrane protein | 850 | 845 ctx | cooccurence:710 |
Rv0588 yrbE2B hyp |
hypothetical protein | 848 | 842 ctx | cooccurence:714 |
Rv0167 yrbE1A |
membrane protein | 832 | 829 ctx | cooccurence:673 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 891 | 826 ctx | cooccurence:636 experimental:431 textmining:400 |
Rv0587 yrbE2A hyp |
hypothetical protein | 827 | 824 ctx | cooccurence:672 |
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 Mce4
- MTBC0 PGAP product: virulence factor Mce family protein
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=5e-19)
- (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_218011.1)
- Domains: Pfam-A via hmmscan --cut_ga — MlaD (PF02470.26)
- 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 I6YC95 (TrEMBL, unreviewed; 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 —
71 functional partner(s); context anchor
mce4D - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003709|Rv3494c|mce4F MIDRLAKIQLSIFAVITVITLSVMAIFYLRLPATFGIGTYGVSADFVAGGGLYKNANVTYRGVAVGRVESVGLNPNGVTAHMRLNSGTAIPSNVTATVRSVSAIGEQYIDLVPPENPSSTKLRNGFRIQRQNTRIGQDVADLLRQAETLLGSLGDTRLRELLHEAFIATNGAGPELARLIESARLLVDEANANYPQVSQLIDQAGPFLQAQIRAGGDIKSLADGLARFTWQLRAADPRLRDTLADAPDAIDEANTAFSGIRPSFPALAASLANLGRVGVIYHKSIEQLLVVFPALFAAIITSAGGVPQDEGAKLDFKIDLHDPPPCMTGFLPPPLVRSPADESVREIPRDMYCKTAQNDPSTVRGARNYPCQEFPGKRAPTVQLCRDPRGYVPVGTNPWRGPPIPYGTEVTDGRNILPPNKFPYIPPGADPDPGVPIVGPPPPGQVAGPGPAPHQPAQPAPPPNDNGPPPPFTSWMPPGYPPEPPQVPYPATIPPPPPPEGTGPPPGPAPGPQPQASGPAYTIYDQLSGAFADPAGGTGIFAPGMTGASSAENWVDLMRDPRQL