mce4C Family assigned · medium auto-curated
H37Rv Rv3497c · MTBC0 mtbc0_003712 ·
357 aa · 3940465–3941538 (-) ·
RefSeq NP_218014.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce4C |
|---|---|
| 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 |
I6YGB1
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mce-family protein Mce4C |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce4C |
| 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 | 0.875 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 | 1.9e-18 | 44–118 | MlaD protein |
Mce4_CUP1 | PF11887.14 | 3.6e-10 | 125–310 | Cholesterol uptake porter CUP1 of Mce4, putative |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lprN (Mce family lipoprotein LprN), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3495c lprN |
Mce family lipoprotein LprN | 996 | 994 ctx | neighborhood:882 cooccurence:774 coexpression:785 textmining:512 |
Rv3494c mce4F |
Mce family protein Mce4 | 999 | 993 ctx | neighborhood:879 cooccurence:766 coexpression:770 textmining:887 |
Rv3498c mce4B |
Mce family protein Mce4B | 991 | 987 ctx | neighborhood:881 coexpression:857 |
Rv3496c mce4D |
Mce family protein Mce4D | 990 | 983 ctx | neighborhood:881 coexpression:805 textmining:447 |
Rv3500c yrbE4B |
integral membrane protein | 991 | 982 ctx | neighborhood:859 cooccurence:773 textmining:543 |
Rv3499c mce4A |
Mce family protein Mce4A | 995 | 979 ctx | neighborhood:881 cooccurence:774 textmining:776 |
Rv3501c yrbE4A |
integral membrane protein | 985 | 975 ctx | neighborhood:815 cooccurence:771 textmining:445 |
Rv3492c |
Mce associated protein | 989 | 970 ctx | neighborhood:879 cooccurence:708 textmining:657 |
Rv3493c |
Mce associated protein | 901 | 902 ctx | neighborhood:879 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 895 | 891 ctx | cooccurence:767 experimental:431 |
Rv1964 yrbE3A |
integral membrane protein | 883 | 881 ctx | cooccurence:768 |
Rv0167 yrbE1A |
membrane protein | 881 | 879 ctx | cooccurence:770 |
Rv0168 yrbE1B |
membrane protein | 885 | 878 ctx | cooccurence:772 |
Rv1965 yrbE3B |
integral membrane protein | 882 | 875 ctx | cooccurence:772 |
Rv0588 yrbE2B hyp |
hypothetical protein | 879 | 875 ctx | cooccurence:772 |
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 Mce4C
- MTBC0 PGAP product: virulence factor Mce family protein
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=2e-18), Mce4_CUP1 PF11887.14 (E=4e-10)
- (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_218014.1)
- 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 I6YGB1 (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 —
39 functional partner(s); context anchor
lprN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003712|Rv3497c|mce4C MLNRKPSSKHERDPLRTGIFGLVLVICVVLIAFGYSGLPFWPQGKTYDAYFTDAGGITPGNSVYVSGLKVGAVSAVSLAGNSAKVTFSVDRSIVVGDQSLAAIRTDTILGERSIAVSPAGSGKSTTIPLSRTTTPYTLNGVLQDLGRNANDLNRPQFEQALNVFTQALHDATPQVRGAVDGLTSLSRALNRRDEALQGLLAHAKSVTSVLSERAEQVNKLVEDGNQLFAALDARRAALSALISGIDDVAAQISGFVADNRKEFGPALSKLNLVLANLNERRDYITEALKRLPTYATTLGEVVGSGPGFNVNVYSVLPGPLVATVFDLVFQPGKLPDSLADYLRGFIQERWIIRPKSP