mce1A Family assigned · medium auto-curated

H37Rv Rv0169 · MTBC0 - · 454 aa · 198534–199898 (+) · RefSeq YP_177701.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Mce family protein Mce1A
MTBC0 PGAP re-annotation
Revised (this work)Mce family protein Mce1A. 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 Q79FZ9 TrEMBL · unreviewed · Evidence at protein level
UniProt nameMce-family protein Mce1A

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namemce1A
eggNOG descriptionVirulence factor Mce family protein
Orthologous groupCOG1463
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 0.925 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 13 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)

PfamAccessioni-EvalueResiduesDescription
MlaDPF02470.26 1.1e-1344–125 MlaD protein
Mce4_CUP1PF11887.14 1.2e-75131–329 Cholesterol uptake porter CUP1 of Mce4, putative

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: yrbE1A (membrane protein), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0167 yrbE1A membrane protein 999 997 ctx neighborhood:882 cooccurence:729 coexpression:881 textmining:811
Rv0168 yrbE1B membrane protein 999 995 ctx neighborhood:799 cooccurence:757 coexpression:868 textmining:824
Rv0170 mce1B Mce family protein Mce1B 998 993 ctx neighborhood:794 cooccurence:772 coexpression:860 textmining:851
Rv0171 mce1C Mce family protein Mce1C 998 993 ctx neighborhood:790 cooccurence:774 coexpression:861 textmining:761
Rv0172 mce1D Mce family protein Mce1D 998 993 ctx neighborhood:784 cooccurence:774 coexpression:860 textmining:826
Rv0173 lprK Mce family lipoprotein LprK 997 991 ctx neighborhood:783 cooccurence:774 coexpression:836 textmining:717
Rv0174 mce1F Mce family protein Mce1F 998 990 ctx neighborhood:785 cooccurence:774 coexpression:805 textmining:828
Rv0655 mkl ABC transporter ATP-binding protein 964 888 ctx cooccurence:692 experimental:431 textmining:699
Rv0166 fadD5 fatty-acid--CoA ligase FadD5 976 886 ctx neighborhood:459 coexpression:798 textmining:804
Rv3500c yrbE4B integral membrane protein 911 869 ctx cooccurence:759
Rv1965 yrbE3B integral membrane protein 901 869 ctx cooccurence:747
Rv0588 yrbE2B hyp hypothetical protein 892 862 ctx cooccurence:754
Rv3501c yrbE4A integral membrane protein 911 854 ctx cooccurence:732 textmining:414
Rv0587 yrbE2A hyp hypothetical protein 908 842 ctx cooccurence:717 textmining:444
Rv1964 yrbE3A integral membrane protein 895 839 ctx cooccurence:699

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 Mce1A
  • Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=1e-13), Mce4_CUP1 PF11887.14 (E=1e-75)
  • (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_177701.1)
  • 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 Q79FZ9 (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 — 79 functional partner(s); context anchor yrbE1A
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0169|mce1A
MTTPGKLNKARVPPYKTAGLGLVLVFALVVALVYLQFRGEFTPKTQLTMLSARAGLVMDPGSKVTYNGVEIGRVDTISEVTRDGESAAKFILDVDPRYIHLIPANVNADIKATTVFGGKYVSLTTPKNPTKRRITPKDVIDVRSVTTEINTLFQTLTSIAEKVDPVKLNLTLSAAAEALTGLGDKFGESIVNANTVLDDLNSRMPQSRHDIQQLAALGDVYADAAPDLFDFLDSSVTTARTINAQQAELDSALLAAAGFGNTTADVFDRGGPYLQRGVADLVPTATLLDTYSPELFCTIRNFYDADPLAKAASGGGNGYSLRTNSEILSGIGISLLSPLALATNGAAIGIGLVAGLIAPPLAVAANLAGALPGIVGGAPNPYTYPENLPRVNARGGPGGAPGCWQPITRDLWPAPYLVMDTGASLAPYNHMEVGSPYAVEYVWGRQVGDNTINP