proZ Family assigned · medium auto-curated

H37Rv Rv3756c · MTBC0 mtbc0_003980 · 239 aa · 4226015–4226734 (-) · RefSeq NP_218273.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ
MTBC0 PGAP re-annotationglycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ
Revised (this work)Glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ. Pfam: BPD_transp_1 (PF00528.28).

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

Curated reference (UniProt)

UniProt O69722 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible osmoprotectant

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred nameproZ
eggNOG descriptioninner membrane component
Orthologous groupCOG1174
KEGG orthology K05846
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 0.136 · 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)

PfamAccessioni-EvalueResiduesDescription
BPD_transp_1PF00528.28 3.5e-1645–207 Binding-protein-dependent transport system inner membrane component

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

Closest characterised functional partner: proV (glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3758c proV glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV 999 1000 ctx neighborhood:881 cooccurence:772 coexpression:869 database:900 textmining:699
Rv3759c proX glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX 999 999 ctx neighborhood:881 fusion:511 cooccurence:774 coexpression:527 database:800 textmining:580
Rv3757c proW glycine betaine/carnitine/choline/L-proline ABC transporter permease ProW 998 998 ctx neighborhood:881 coexpression:805 database:900
Rv3755c hyp hypothetical protein 883 883 ctx neighborhood:881
Rv3760 membrane protein 769 769 ctx neighborhood:768
Rv1244 lpqZ lipoprotein LpqZ 783 762 ctx cooccurence:469 coexpression:516
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 448 73 textmining:430
Rv0191 MFS-type transporter 661 64 textmining:653
Rv0404 fadD30 long-chain-fatty-acid--AMP ligase FadD30 439 53 textmining:432
Rv1667c Rv1667c, (MTV047.03c), len: 217 aa. Probable second part of macrolide-transport ATP-binding protein ABC transporter (see citation below), wi 659 51 textmining:656
Rv3008 hyp hypothetical protein 809 44 textmining:809
Rv0323c hyp hypothetical protein 631 44 textmining:630
Rv2080 lppJ lipoprotein LppJ 517 44 textmining:516
Rv0565c monooxygenase 512 44 textmining:511
Rv3601c panD aspartate 1-decarboxylase 438 44 textmining:437

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 permease ProZ
  • MTBC0 PGAP product: glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ
  • Pfam (hmmscan --cut_ga): BPD_transp_1 PF00528.28 (E=4e-16)
  • (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_218273.1)
  • Domains: Pfam-A via hmmscan --cut_ga — BPD_transp_1 (PF00528.28)
  • 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 COG1174
  • Curated reference: UniProt O69722 (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 — 16 functional partner(s); context anchor proV
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003980|Rv3756c|proZ
MNFLQQALSYLLTASNWTGPVGLAVRTCEHLEYTAVAVAASALIAVPVGLLIGHTGRGTLLVVGAVNGLRALPTLGVLLLGVLLFGLGLGPPLVALMLLGIPSLLASTYAGIASVDPLVVDAARAMGMTESQVLLRVEVPNALPLMLGGLRSATLQVVATATVAAYASLGGLGGYLIDGIKERRFHIALVGAMMVAALALTLDGLLALAGWVSVPGTGRMRKLAAVVDKPAAGGGHALR