drrA Family assigned · medium auto-curated

H37Rv Rv2936 · MTBC0 mtbc0_003119 · 331 aa · 3293211–3294206 (+) · RefSeq NP_217452.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)daunorubicin ABC transporter ATP-binding protein DrrA
MTBC0 PGAP re-annotationdaunorubicin ABC transporter ATP-binding protein DrrA
Revised (this work)Daunorubicin ABC transporter ATP-binding protein DrrA. 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 P9WQL9 SwissProt · reviewed · Evidence at protein level
UniProt nameDoxorubicin resistance ATP-binding protein DrrA
EC (curated) EC 7.6.2.-
Curated functionPart of the ABC transporter complex DrrABC involved in doxorubicin resistance. Responsible for energy coupling to the transport system. Binds ATP.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
Preferred namedrrA
eggNOG descriptionABC transporter
Orthologous groupCOG1131
KEGG orthology K01990
KEGG modules M00254
Gene Ontology (46) GO:0000166, GO:0003674, GO:0005488, GO:0005524, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0006869, GO:0008144, GO:0008150 +34 more

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 0.689 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 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 3.4e-3025–169 ABC transporter

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

Closest characterised functional partner: drrB (daunorubicin ABC transporter permease DrrB), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2937 drrB daunorubicin ABC transporter permease DrrB 999 997 ctx neighborhood:881 cooccurence:728 coexpression:913 textmining:948
Rv2938 drrC daunorubicin ABC transporter permease DrrC 999 996 ctx neighborhood:836 cooccurence:764 coexpression:913 textmining:807
Rv2935 ppsE phthiocerol synthesis polyketide synthase type I PpsE 993 981 ctx neighborhood:867 coexpression:860 textmining:672
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 985 974 ctx neighborhood:874 coexpression:777 textmining:457
Rv2934 ppsD phthiocerol synthesis polyketide synthase type I PpsD 955 952 ctx neighborhood:760 coexpression:810
Rv2939 papA5 phthiocerol/phthiodiolone dimycocerosyl transferase 983 947 ctx neighborhood:668 coexpression:848 textmining:697
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 938 832 ctx neighborhood:786 textmining:648
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 813 797 ctx neighborhood:786
Rv2930 fadD26 fatty-acid--CoA ligase FadD26 897 784 ctx neighborhood:767 textmining:546
Rv3758c proV glycine betaine/carnitine/choline/L-proline ABC transporter ATP-binding protein ProV 678 678 ctx fusion:641
Rv0194 multidrug ABC transporter ATPase/permease 673 636 database:536
Rv1273c drug ABC transporter ATP-binding protein 648 632 database:536
Rv1272c drug ABC transporter ATP-binding protein 648 632 database:536
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 641 619 database:536
Rv1349 irtB iron ABC transporter ATP-binding protein/permease IrtB 634 618 database:536

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: daunorubicin ABC transporter ATP-binding protein DrrA
  • MTBC0 PGAP product: daunorubicin ABC transporter ATP-binding protein DrrA
  • Pfam (hmmscan --cut_ga): ABC_tran PF00005.34 (E=3e-30)
  • (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_217452.1)
  • 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 COG1131
  • Curated reference: UniProt P9WQL9 (SwissProt, reviewed; 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 — 44 functional partner(s); context anchor drrB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003119|Rv2936|drrA
MRNDDMAVVVNGVRKTYGKGKIVALDDVSFKVRRGEVIGLLGPNGAGKTTMVDILSTLTRPDAGSAIIAGYDVVSEPAGVRRSIMVTGQQVAVDDALSGEQNLVLFGRLWGLSKSAARKRAAELLEQFSLVHAGKRRVGTYSGGMRRRIDIACGLVVQPQVAFLDEPTTGLDPRSRQAIWDLVASFKKLGIATLLTTQYLEEADALSDRIILIDHGIIIAEGTANELKHRAGDTFCEIVPRDLKDLDAIVAALGSLLPEHHRAMLTPDSDRITMPAPDGIRMLVEAARRIDEARIELADIALRRPSLDDVFLAMTTDPTESLTHLVSGSAR