yrbE4B Family assigned · medium auto-curated

H37Rv Rv3500c · MTBC0 mtbc0_003715 · 280 aa · 3943802–3944644 (-) · RefSeq NP_218017.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane protein
MTBC0 PGAP re-annotationABC transporter permease
Revised (this work)ABC transporter permease. Pfam: MlaE (PF02405.22).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt I6Y3P5 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved integral membrane protein YrbE4B. Possible ABC transporter

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred nameyrbE4B
eggNOG descriptionABC-type transport system involved in resistance to organic solvents, permease component
Orthologous groupCOG0767
KEGG orthology K02066
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 0.122 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 2 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
MlaEPF02405.22 7.8e-5463–267 Permease MlaE

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

Closest characterised functional partner: mkl (ABC transporter ATP-binding protein), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0655 mkl ABC transporter ATP-binding protein 990 987 ctx cooccurence:774 coexpression:457 experimental:505 database:800
Rv3499c mce4A Mce family protein Mce4A 995 984 ctx neighborhood:859 cooccurence:768 textmining:737
Rv3497c mce4C Mce family protein Mce4C 991 982 ctx neighborhood:859 cooccurence:773 textmining:543
Rv3498c mce4B Mce family protein Mce4B 993 981 ctx neighborhood:859 cooccurence:773 textmining:665
Rv3496c mce4D Mce family protein Mce4D 991 981 ctx neighborhood:859 cooccurence:773 textmining:539
Rv3495c lprN Mce family lipoprotein LprN 986 981 ctx neighborhood:859 cooccurence:770
Rv3494c mce4F Mce family protein Mce4 995 977 ctx neighborhood:856 cooccurence:736 textmining:815
Rv3501c yrbE4A integral membrane protein 960 936 ctx neighborhood:833 textmining:407
Rv3492c Mce associated protein 917 917 ctx neighborhood:856 cooccurence:440
Rv0170 mce1B Mce family protein Mce1B 882 878 ctx cooccurence:773
Rv1971 mce3F Mce family protein Mce3F 902 875 ctx cooccurence:772
Rv0173 lprK Mce family lipoprotein LprK 902 874 ctx cooccurence:770
Rv0172 mce1D Mce family protein Mce1D 878 874 ctx cooccurence:766
Rv0590 mce2B Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( 908 872 ctx cooccurence:773
Rv0592 mce2D Mce family protein Mce2D 908 872 ctx cooccurence:771

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: integral membrane protein
  • MTBC0 PGAP product: ABC transporter permease
  • Pfam (hmmscan --cut_ga): MlaE PF02405.22 (E=8e-54)
  • (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_218017.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MlaE (PF02405.22)
  • 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 COG0767
  • Curated reference: UniProt I6Y3P5 (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 — 49 functional partner(s); context anchor mkl
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003715|Rv3500c|yrbE4B
MSYDVTIRFRRFFSRLQRPVDNFGEQALFYGETMRYVPNAITRYRKETVRLVAEMTLGAGALVMIGGTVGVAAFLTLASGGVIAVQGYSSLGDIGIEALTGFLSAFLNVRVVAPVIAGIALAATIGAGATAQLGAMRVSEEIDAVECMAVHSVSYLVSTRLIAGLVAIIPLYSLSVLAAFFAARFTTVFVNGQSAGLYDHYFNTFLIPSDLLWSFMQAIAMSIAVMLVHTYYGYNASGGSVGVGVAVGQAVRTSLIVVVVITLFISLAVYGASGNFNLSG