dppA Family assigned · medium auto-curated

H37Rv Rv3666c · MTBC0 mtbc0_003884 · 541 aa · 4129289–4130914 (-) · RefSeq NP_218183.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)dipeptide ABC transporter substrate-binding lipoprotein DppA
MTBC0 PGAP re-annotationABC transporter substrate-binding protein
Revised (this work)ABC transporter substrate-binding protein. Pfam: SBP_bac_5 (PF00496.28).

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

Curated reference (UniProt)

UniProt I6X811 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable periplasmic dipeptide-binding lipoprotein DppA

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namedppA
eggNOG descriptionBacterial extracellular solute-binding proteins, family 5 Middle
Orthologous groupCOG4166
KEGG orthology K02035, K15580
KEGG pathways map01501, map02010, map02024
KEGG modules M00239, M00439

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 0.666 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (241) · clonal

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
SBP_bac_5PF00496.28 5.6e-5277–462 Bacterial extracellular solute-binding proteins, family 5 Middle

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

Closest characterised functional partner: dppB (dipeptide ABC transporter permease DppB), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3665c dppB dipeptide ABC transporter permease DppB 998 998 ctx neighborhood:882 cooccurence:772 coexpression:475 database:900
Rv3664c dppC dipeptide ABC transporter permease DppC 998 997 ctx neighborhood:807 cooccurence:768 coexpression:425 database:900 textmining:665
Rv3663c dppD dipeptide ABC transporter ATP-binding protein DppD 998 996 ctx neighborhood:807 cooccurence:677 database:900 textmining:562
Rv3662c hyp hypothetical protein 864 808 ctx neighborhood:807
Rv1283c oppB oligopeptide ABC transporter permease OppB 881 778 ctx cooccurence:550 coexpression:470 textmining:487
Rv1282c oppC oligopeptide ABC transporter permease OppC 798 771 ctx cooccurence:575 coexpression:416
Rv0783c emrB multidrug resistance protein EmrB 751 751 coexpression:751
Rv2326c ABC transporter ATP-binding protein 705 666
Rv3667 acs acetyl-CoAsynthetase 563 563 ctx neighborhood:544
Rv1281c oppD oligopeptide ABC transporter ATP-binding protein OppD 621 465
Rv1280c oppA oligopeptide ABC transporter substrate-binding lipoprotein OppA 742 445 textmining:555
Rv0928 pstS3 phosphate ABC transporter substrate-binding lipoprotein PstS 425 388
Rv1244 lpqZ lipoprotein LpqZ 524 365
Rv0934 pstS1 phosphate ABC transporter substrate-binding lipoprotein PstS 453 364
Rv3759c proX glycine betaine/carnitine/choline/L-proline ABC transporter substrate-binding lipoprotein ProX 401 364

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: dipeptide ABC transporter substrate-binding lipoprotein DppA
  • MTBC0 PGAP product: ABC transporter substrate-binding protein
  • Pfam (hmmscan --cut_ga): SBP_bac_5 PF00496.28 (E=6e-52)
  • (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_218183.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SBP_bac_5 (PF00496.28)
  • 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 COG4166
  • Curated reference: UniProt I6X811 (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 — 17 functional partner(s); context anchor dppB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003884|Rv3666c|dppA
MVRRMRAALAALATGLLVLAPVAGCGGGVLSPDVVLVNGGEPPNPLIPTGTNDSNGGRIIDRLFAGLMSYDAVGKPSLEVAQSIESADNVNYRITVKPGWKFTDGSPVTAHSFVDAWNYGALSTNAQLQQHFFSPIEGFDDVAGAPGDKSRTTMSGLRVVNDLEFTVRLKAPTIDFTLRLGHSSFYPLPDSAFRDMAAFGRNPIGNGPYKLADGPAGPAWEHNVRIDLVPNPDYHGNRKPRNKGLRFEFYANLDTAYADLLSGNLDVLDTIPPSALTVYQRDLGDHATSGPAAINQTLDTPLRLPHFGGEEGRLRRLALSAAINRPQICQQIFAGTRSPARDFTARSLPGFDPNLPGNEVLDYDPQRARRLWAQADAISPWSGRYAIAYNADAGHRDWVDAVANSIKNVLGIDAVAAPQPTFAGFRTQITNRAIDSAFRAGWQGDYPSMIEFLAPLFTAGAGSNDVGYINPEFDAALAAAEAAPTLTESHELVNDAQRILFHDMPVVPLWDYISVVGWSSQVSNVTVTWNGLPDYENIVKA