arsA Family assigned · medium auto-curated

H37Rv Rv2684 · MTBC0 mtbc0_002858 · 429 aa · 3023029–3024318 (+) · RefSeq NP_217200.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)arsenic-transport integral membrane protein ArsA
MTBC0 PGAP re-annotationArsB/NhaD family transporter
Revised (this work)ArsB/NhaD family transporter. Pfam: ArsB (PF02040.21), CitMHS (PF03600.23), Na_sulph_symp (PF00939.26).

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

Curated reference (UniProt)

UniProt P9WPD9 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized transporter Rv2684

UniProt still lists this protein as Uncharacterized transporter Rv2684; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namearsA
eggNOG descriptiontransport of arsenical compounds across the membrane (export) arsenic resistance by an export mechanism. responsible for the translocation of the substrate across the membrane
Orthologous groupCOG1055
KEGG orthology K03893

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 0.649 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (242) · 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
ArsBPF02040.21 3.1e-195–422 Arsenical pump membrane protein
CitMHSPF03600.23 2.3e-8513–367 Citrate transporter
Na_sulph_sympPF00939.26 3.1e-08230–421 Sodium:sulfate symporter transmembrane region

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

Closest characterised functional partner: arsB1 (arsenic-transport integral membrane protein ArsB), medium confidence from genomic context alone (score 636 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2683 hyp hypothetical protein 950 950 ctx neighborhood:801 cooccurence:723
Rv2685 arsB1 arsenic-transport integral membrane protein ArsB 637 636 ctx neighborhood:577
Rv2682c dxs1 1-deoxy-D-xylulose 5-phosphate synthase 543 543 ctx neighborhood:542
Rv0053 rpsF 30S ribosomal protein S6 411 412 coexpression:410
Rv2643 arsC arsenic-transport integral membrane protein ArsC 405 161
Rv0125 pepA serine protease PepA 572 51 textmining:568
Rv1607 chaA ionic transporter integral membrane protein ChaA 461 51 textmining:456
Rv0527 ccdA cytochrome C-type biogenesis protein CcdA 438 45 textmining:436
Rv2608 PPE42 PPE family protein PPE42 445 44 textmining:444

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: arsenic-transport integral membrane protein ArsA
  • MTBC0 PGAP product: ArsB/NhaD family transporter
  • Pfam (hmmscan --cut_ga): ArsB PF02040.21 (E=3e-19), CitMHS PF03600.23 (E=2e-85), Na_sulph_symp PF00939.26 (E=3e-08)
  • (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_217200.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ArsB (PF02040.21), CitMHS (PF03600.23), Na_sulph_symp (PF00939.26)
  • 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 COG1055
  • Curated reference: UniProt P9WPD9 (SwissProt, reviewed; Inferred from homology)
  • 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 — 9 functional partner(s); context anchor arsB1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002858|Rv2684|arsA
MSVVAVTIFVAAYVLIASDRVNKTMVALTGAAAVVVLPVITSHDIFYSHDTGIDWDVIFLLVGMMIIVGVLRQTGVFEYTAIWAAKRARGSPLRIMILLVLVSALASALLDNVTTVLLIAPVTLLVCDRLNINTTSFLMAEVFASNIGGAATLVGDPPNIIVASRAGLTFNDFMLHLTPLVVIVLIALIAVLPRLFGSITVEADRIADVMALDEGEAIRDRGLLVKCGAVLVLVFAAFVAHPVLHIQPSLVALLGAGMLIVVSGLTRSEYLSSVEWDTLLFFAGLFIMVGALVKTGVVNDLARAATQLTGGNIVATAFLILGVSAPISGIIDNIPYVATMTPLVAELVAVMGGQPSTDTPWWALALGADFGGNLTAIGASANVVMLGIARRAGAPISFWEFTRKGAVVTAVSIALAAIYLWLRYFVLLH