Rv2508c Resolved · high auto-curated

H37Rv Rv2508c · MTBC0 mtbc0_002670 · 445 aa · 2846146–2847483 (-) · RefSeq NP_217024.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane protein
MTBC0 PGAP re-annotationMFS transporter
Revised (this work)MFS transporter. Pfam: MFS_1 (PF07690.22), ATG22 (PF11700.15).

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

Curated reference (UniProt)

UniProt O06171 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved integral membrane leucine and alanine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionMajor facilitator superfamily
Orthologous groupCOG2270
KEGG orthology K06902
KEGG pathways map04138

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 3.492 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 9 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
MFS_1PF07690.22 3.0e-1635–396 Major Facilitator Superfamily
ATG22PF11700.15 3.5e-24149–434 Vacuole effluxer Atg22 like

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

Closest characterised functional partner: cmrA (short-chain type dehydrogenase/reductase), high confidence from genomic context alone (score 784 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2509 cmrA short-chain type dehydrogenase/reductase 784 784 ctx neighborhood:783
Rv0317c glpQ2 glycerophosphoryl diester phosphodiesterase GlpQ 401 402

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: integral membrane protein
  • MTBC0 PGAP product: MFS transporter
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=3e-16), ATG22 PF11700.15 (E=3e-24)
  • (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_217024.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22), ATG22 (PF11700.15)
  • 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 COG2270
  • Curated reference: UniProt O06171 (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 — 2 functional partner(s); context anchor cmrA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002670|Rv2508c|
MNNPGSRAGTLLHFRVVAWAMWDCGSTGLNAIVTTFVFSVYLTSAVGQGLPGGTSPASWLGRAGAVAGLTIGVLAPVVGVWVESPHRRRVALSVLTGTAVALTCAMFLIRDDPRYLWAGLVLLAATAASSDLSSVPYNAMLRQLSTPSTAGRISGFGWASGYVGSVALLLVIYLGFMSGSGSQRGLLQLPVANGLNVRMAMLVAAAWLALLGLPLLLVAHRLPDSGAASHPSTGLLGGYRKLWTEISAEWRRDRNLVYFLVASAIFRDGLAAIFAFGAVLGVNAYGLTQADVLIFGAAASVVAAVGAVLGGFVDHRIGSKPVIVGSLAAIIAAALTLLTLSGPTAFWACGLLLCVFIGPAQSSARALLLHMAQHGKEGVAFGLYTMTGRAVSFLGPWLFSVFVDVFHTVRAGLGGVCLVLTTGLLLMLRVQVSRHGGALTTAQSS