Rv3737 Family assigned · medium auto-curated

H37Rv Rv3737 · MTBC0 mtbc0_003962 · 529 aa · 4211820–4213409 (+) · RefSeq NP_218254.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationthreonine/serine exporter family protein
Revised (this work)Threonine/serine exporter family protein. Pfam: ThrE (PF06738.19), ThrE_2 (PF12821.14).

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

Curated reference (UniProt)

UniProt O69704 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable threonine/serine exporter
Curated functionCatalyzes the export of L-threonine and L-serine from the cell to the extracellular environment (By similarity). Export is dependent on the proton motive force (By similarity). Required for in vitro growth and survival of bacteria inside macrophages. Increased expression is associated with low-level amikacin (AMK) resistance.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionThreonine/Serine exporter, ThrE
Orthologous groupCOG2966

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 0.572 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 9 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (202) · 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
ThrEPF06738.19 1.3e-6350–287 Putative threonine/serine exporter
ThrE_2PF12821.14 8.2e-11323–446 Threonine/Serine exporter, ThrE

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

Closest characterised functional partner: Rv3736 (AraC/XylS family transcriptional regulator), high confidence from genomic context alone (score 805 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3736 AraC/XylS family transcriptional regulator 973 805 ctx neighborhood:801 textmining:870
Rv3882c eccE1 ESX-1 secretion system protein EccE1 668 668 ctx cooccurence:668
Rv3735 hyp hypothetical protein 647 647 ctx neighborhood:646
Rv3877 eccD1 ESX-1 secretion system protein EccD1 602 603 ctx cooccurence:600
Rv1407 fmu 16S rRNA m5C967 methyltransferase 568 568 ctx neighborhood:544
Rv1832 gcvB glycine dehydrogenase 567 567 ctx neighborhood:544
Rv0014c pknB serine/threonine-protein kinase PknB 550 550 ctx neighborhood:544
Rv0931c pknD serine/threonine-protein kinase PknD 549 550 ctx neighborhood:544
Rv0901 arfC membrane protein 546 547 ctx cooccurence:544
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 545 545 ctx neighborhood:544
Rv0658c integral membrane protein 544 544 ctx cooccurence:541
Rv2416c eis enhanced intracellular survival protein 540 541 ctx cooccurence:475
Rv2124c metH methionine synthase 539 539 ctx neighborhood:539
Rv1226c transmembrane protein 482 482 ctx cooccurence:463
Rv3875 esxA ESAT-6 protein EsxA 469 470 ctx cooccurence:467

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: transmembrane protein
  • MTBC0 PGAP product: threonine/serine exporter family protein
  • Pfam (hmmscan --cut_ga): ThrE PF06738.19 (E=1e-63), ThrE_2 PF12821.14 (E=8e-11)
  • (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_218254.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ThrE (PF06738.19), ThrE_2 (PF12821.14)
  • 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 COG2966
  • Curated reference: UniProt O69704 (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 — 33 functional partner(s); context anchor Rv3736
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003962|Rv3737|
MDQDRSDNTALRRGLRIALRGRRDPLPVAGRRSRTSGGIGDLHTRKVLDLTIRLAEVMLSSGSGTADVVATAQDVAQAYQLTDCVVDITVTTIIVSALATTDTPPVTIMRSVRTRSTDYSRLAELDRLVQRITSGGVAVDQAHEAMDELTERPHPYPRWLATAGAAGFALGVAMLLGGTWLTCVLAAVTSGVIDRLGRLLNRIGTPLFFQRVFGAGIATLVAVAAYLIAGQDPTALVATGIVVLLSGMTLVGSMQDAVTGYMLTALARLGDALFLTAGIVVGILISLRGVTNAGIQIELHVDATTTLATPGMPLPILVAVSGAALSGVCLTIASYAPLRSVATAGLSAGLAELVLIGLGAAGFGRVVATWTAAIGVGFLATLISIRRQAPALVTATAGIMPMLPGLAVFRAVFAFAVNDTPDGGLTQLLEAAATALALGSGVVLGEFLASPLRYGAGRIGDLFRIEGPPGLRRAVGRVVRLQPAKSQQPTGTGGQRWRSVALEPTTADDVDAGYRGDWPATCTSATEVR