proX Family assigned · medium auto-curated

H37Rv Rv3759c · MTBC0 mtbc0_003983 · 315 aa · 4228547–4229494 (-) · RefSeq NP_218276.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX
MTBC0 PGAP re-annotationglycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding protein ProX
Revised (this work)Glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding protein ProX. Pfam: OpuAC (PF04069.18).

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

Curated reference (UniProt)

UniProt O69725 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible osmoprotectant

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameproX
eggNOG descriptionGlycine betaine
Orthologous groupCOG1732
KEGG orthology K05845
KEGG pathways map02010
KEGG modules M00209

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 0.605 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 10 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
OpuACPF04069.18 9.5e-5241–305 Substrate binding domain of ABC-type glycine betaine transport system

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

Closest characterised functional partner: proZ (glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3756c proZ glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ 999 999 ctx neighborhood:881 fusion:511 cooccurence:774 coexpression:527 database:800 textmining:580
Rv3758c proV glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV 999 999 ctx neighborhood:882 cooccurence:769 coexpression:775 database:800 textmining:692
Rv3757c proW glycine betaine/carnitine/choline/L-proline ABC transporter permease ProW 999 998 ctx neighborhood:882 cooccurence:774 coexpression:536 database:800 textmining:711
Rv3755c hyp hypothetical protein 903 903 ctx neighborhood:881
Rv1244 lpqZ lipoprotein LpqZ 789 789 ctx cooccurence:684
Rv3760 membrane protein 771 771 ctx neighborhood:768
Rv1234 transmembrane protein 739 740 coexpression:706
Rv2060 integral membrane protein 434 435
Rv3470c ilvB2 acetolactate synthase large subunit 420 420 coexpression:417
Rv0888 spmT hyp hypothetical protein 409 409 coexpression:409
Rv0932c pstS2 phosphate ABC transporter substrate-binding lipoprotein PstS 527 383
Rv0928 pstS3 phosphate ABC transporter substrate-binding lipoprotein PstS 408 380
Rv0934 pstS1 phosphate ABC transporter substrate-binding lipoprotein PstS 456 376
Rv3666c dppA dipeptide ABC transporter substrate-binding lipoprotein DppA 401 364
Rv1280c oppA oligopeptide ABC transporter substrate-binding lipoprotein OppA 541 363

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: glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX
  • MTBC0 PGAP product: glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding protein ProX
  • Pfam (hmmscan --cut_ga): OpuAC PF04069.18 (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 NP_218276.1)
  • Domains: Pfam-A via hmmscan --cut_ga — OpuAC (PF04069.18)
  • 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 COG1732
  • Curated reference: UniProt O69725 (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 — 33 functional partner(s); context anchor proZ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003983|Rv3759c|proX
MRMLRRLRRATVAAAVWLATVCLVASCANADPLGSATGSVKSIVVGSGDFPESQVIAEIYAQVLQANGFDVGRRLGIGSRETYIPALKDHSIDLVPEYIGNLLLYFQPDATVTMLDAVELELYKRLPGDLSILTPSPASDTDTVTVTAATAARWNLKTIADLAPHSADVKFAAPSAFQTRPSGLPGLRHKYSLDIAPGNFVTINDGGGAVTVRALVEGTATAANLFSTSAAIPQNHLVVLEDPEHNFLAGNIVPLVNSRKKSDHLKDVLDAVSAKLTTAGLAELNAAVSGNSGVDPDQAARKWVRDNGFDHPVRQ