mce4A Family assigned · medium auto-curated
H37Rv Rv3499c · MTBC0 - ·
400 aa · 3917998–3919200 (-) ·
RefSeq YP_177977.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Mce family protein Mce4A |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Mce family protein Mce4A. 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 |
I6YC99
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mce-family protein Mce4A |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mce4A |
| 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 | 0.116 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 | 6.8e-17 | 40–118 | MlaD protein |
Mce4_CUP1 | PF11887.14 | 9.5e-52 | 122–340 | Cholesterol uptake porter CUP1 of Mce4, putative |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mce4B (Mce family protein Mce4B), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3498c mce4B |
Mce family protein Mce4B | 996 | 993 ctx | neighborhood:882 cooccurence:773 coexpression:761 textmining:579 |
Rv3500c yrbE4B |
integral membrane protein | 995 | 984 ctx | neighborhood:859 cooccurence:768 textmining:737 |
Rv3497c mce4C |
Mce family protein Mce4C | 995 | 979 ctx | neighborhood:881 cooccurence:774 textmining:776 |
Rv3496c mce4D |
Mce family protein Mce4D | 987 | 978 ctx | neighborhood:881 cooccurence:774 textmining:472 |
Rv3495c lprN |
Mce family lipoprotein LprN | 978 | 973 ctx | neighborhood:881 cooccurence:774 |
Rv3492c |
Mce associated protein | 975 | 971 ctx | neighborhood:879 cooccurence:762 |
Rv3501c yrbE4A |
integral membrane protein | 983 | 952 ctx | neighborhood:669 cooccurence:752 textmining:662 |
Rv3494c mce4F |
Mce family protein Mce4 | 960 | 918 ctx | neighborhood:879 textmining:540 |
Rv3493c |
Mce associated protein | 882 | 883 ctx | neighborhood:879 |
Rv0168 yrbE1B |
membrane protein | 907 | 867 ctx | cooccurence:761 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 930 | 865 ctx | cooccurence:718 experimental:431 textmining:507 |
Rv0588 yrbE2B hyp |
hypothetical protein | 892 | 865 ctx | cooccurence:760 |
Rv1965 yrbE3B |
integral membrane protein | 874 | 862 ctx | cooccurence:755 |
Rv0167 yrbE1A |
membrane protein | 892 | 859 ctx | cooccurence:741 |
Rv0587 yrbE2A hyp |
hypothetical protein | 886 | 851 ctx | cooccurence:735 |
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 Mce4A
- Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=7e-17), Mce4_CUP1 PF11887.14 (E=1e-51)
- (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_177977.1)
- 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 I6YC99 (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 —
88 functional partner(s); context anchor
mce4B - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3499c|mce4A MSGGGSRRTSVRVAAALLAGLMVGSAVLTYLSYTAAFTSTDTVTVSSPRAGLVMEKGAKVKYRGIQVGKVTDISYSGNQARLKLAIDSGEMGFIPSNATVRIAGNTIFGAKSVEFIPPKTPSPKPLSPNAHVAASQVQLEVNTLFQSLIDLLHKIDPLETNATLSALSEGLRGHGDDLGALLSGLNTLTRQANPKLPALQEDFRKAAVVANVYADAAGDLNTVFDNLPTINKTIVDQKDNLNDTLLATIGLSNNAYETLAPAEQNFIDAINRLRAPLKVTSDYSPVFGCLFKGIARGVKEFAPLIGVRKAGLFTSSSFVLGAPSYTYPESLPIVNASGGPNCRGLPDIPTKQTGGSFYRAPFLVTDNALIPYQPFTELQVDAPSTLQFLFNGAFAERDDF