proV Family assigned · medium auto-curated

H37Rv Rv3758c · MTBC0 mtbc0_003982 · 376 aa · 4227408–4228538 (-) · RefSeq NP_218275.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV
MTBC0 PGAP re-annotationglycine betaine/L-proline ABC transporter ATP-binding protein ProV
Revised (this work)Glycine betaine/L-proline ABC transporter ATP-binding protein ProV. Pfam: ABC_tran (PF00005.34).

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

Curated reference (UniProt)

UniProt O69724 TrEMBL · unreviewed · Evidence at protein level
UniProt nameABC-type quaternary amine transporter
EC (curated) EC 7.6.2.9

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameproV
eggNOG descriptionABC transporter
Orthologous groupCOG1125
KEGG orthology K05847
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 0.898 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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
ABC_tranPF00005.34 1.9e-3219–163 ABC transporter

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 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3756c proZ glycine betaine/carnitine/choline/L-proline ABC transporter permease ProZ 999 1000 ctx neighborhood:881 cooccurence:772 coexpression:869 database:900 textmining:699
Rv3757c proW glycine betaine/carnitine/choline/L-proline ABC transporter permease ProW 999 1000 ctx neighborhood:882 cooccurence:773 coexpression:954 database:900 textmining:829
Rv3759c proX glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX 999 999 ctx neighborhood:882 cooccurence:769 coexpression:775 database:800 textmining:692
Rv1244 lpqZ lipoprotein LpqZ 902 889 ctx cooccurence:500 coexpression:726
Rv3755c hyp hypothetical protein 888 888 ctx neighborhood:881
Rv3760 membrane protein 775 775 ctx neighborhood:768
Rv2936 drrA daunorubicin ABC transporter ATP-binding protein DrrA 678 678 ctx fusion:641
Rv3336c trpS tryptophan--tRNA ligase 510 510 coexpression:494
Rv2688c antibiotic ABC transporter ATP-binding protein 408 408
Rv0204c transmembrane protein 431 406 coexpression:406
Rv0585c integral membrane protein 431 406 coexpression:406
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 663 77 textmining:650
Rv3534c hsaF 4-hydroxy-2-oxovalerate aldolase 529 76 textmining:512
Rv2391 sirA sulfite reductase 530 51 textmining:526
Rv2072c cobL precorrin-6Y C(5,15)-methyltransferase 658 44 textmining:657

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 ATP-binding protein ProV
  • MTBC0 PGAP product: glycine betaine/L-proline ABC transporter ATP-binding protein ProV
  • Pfam (hmmscan --cut_ga): ABC_tran PF00005.34 (E=2e-32)
  • (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_218275.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ABC_tran (PF00005.34)
  • 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 COG1125
  • Curated reference: UniProt O69724 (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 proZ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003982|Rv3758c|proV
MICFDDVSKVYAHGATAVDRLTLEVPNGMLTVFVGPSGCGKTTALRMINRMVDPTSGTITVDGTDVSTVNAVKLRLGIGYVIQNAGLMPHQRVIDNVATVPVLKGQPRRAARKAGYEVLERVGLDPKVATRYPAQLSGGEQQRVGVARALAADPPILLMDEPFSAVDPVVRHELQNEILRLQAELHKTIVFVTHDIDEALKLADLVAVFAPGGALAQYDETARLLSSPANDFVSKFIGLGRGYRWLQLFDAAGLPVRDIEQVSVNGLSDARDRQVRDGWVLVVDGAGAPLGWIDADGRRRHRGGAALSDAMTVGGSVFRPNGNLSQALDAALSSPSGVGVAVDGGGKVIGGILAADVLAEFQKGKKAGGGAKPCTT