Rv2366c Family assigned · medium auto-curated

H37Rv Rv2366c · MTBC0 mtbc0_002518 · 435 aa · 2671253–2672560 (-) · RefSeq NP_216882.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationhemolysin family protein
Revised (this work)Hemolysin family protein. Pfam: CNNM (PF01595.26), CBS (PF00571.34), CorC_HlyC (PF03471.23).

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

Curated reference (UniProt)

UniProt P9WFP1 SwissProt · reviewed · Evidence at protein level
UniProt nameUPF0053 protein Rv2366c

UniProt still lists this protein as UPF0053 protein Rv2366c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namecorC
eggNOG descriptionCBS domain
Orthologous groupCOG1253
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 1.78 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 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
CNNMPF01595.26 5.2e-359–185 Cyclin M transmembrane N-terminal domain
CBSPF00571.34 5.1e-07269–323 CBS domain
CorC_HlyCPF03471.23 7.6e-12341–400 Transporter associated domain

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

Closest characterised functional partner: ybeY (endoribonuclease), high confidence from genomic context alone (score 988 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2367c ybeY endoribonuclease 988 988 ctx neighborhood:882 coexpression:887
Rv2365c hyp hypothetical protein 982 983 ctx neighborhood:882 coexpression:860
Rv2368c phoH1 phosphate starvation-inducible protein PhoH 976 976 ctx neighborhood:881 coexpression:806
Rv2364c era GTPase Era 966 966 ctx neighborhood:791 coexpression:844
Rv3608c folP1 dihydropteroate synthase 793 793 coexpression:793
Rv2369c hyp hypothetical protein 775 774 ctx neighborhood:773
Rv2370c hyp hypothetical protein 774 773 ctx neighborhood:773
Rv2373c dnaJ2 chaperone protein DnaJ 689 690 ctx neighborhood:544
Rv2372c rsmE rRNA small subunit methyltransferase E 548 548 ctx neighborhood:544
Rv2374c hrcA heat-inducible transcription repressor HrcA 535 536 ctx neighborhood:529
Rv2371 PE_PGRS40 PE-PGRS family protein PE_PGRS40 497 497 ctx neighborhood:497
Rv3455c truA tRNA pseudouridine synthase A 454 455 ctx cooccurence:428
Rv2553c mltG membrane protein 436 433 coexpression:415
Rv2725c hflX GTP-binding protein HflX 401 402
Rv0352 dnaJ1 chaperone protein DnaJ 401 401

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: hemolysin family protein
  • Pfam (hmmscan --cut_ga): CNNM PF01595.26 (E=5e-35), CBS PF00571.34 (E=5e-07), CorC_HlyC PF03471.23 (E=8e-12)
  • (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_216882.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CNNM (PF01595.26), CBS (PF00571.34), CorC_HlyC (PF03471.23)
  • 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 COG1253
  • Curated reference: UniProt P9WFP1 (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 — 16 functional partner(s); context anchor ybeY
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002518|Rv2366c|
MTGYYQLLGSIVLIGLGGLFAAIDAAISTVSPARVDELVRDQRPGAGSLRKVMADRPRYVNLVVLLRTSCEITATALLVVFIRYHFSMVWGLYLAAGIMVLASFVVVGVGPRTLGRQNAYSISLATALPLRLISWLLMPISRLLVLLGNALTPGRGFRNGPFASEIELREVVDLAQQRGVVAADERRMIESVFELGDTPAREVMVPRTEMIWIESDKTAGQAMTLAVRSGHSRIPVIGENVDDIVGVVYLKDLVEQTFCSTNGGRETTVARVMRPAVFVPDSKPLDALLREMQRDRNHMALLVDEYGAIAGLVSIEDVLEEIVGEIADEYDQAETAPVEDLGDKRFRVSARLPIEDVGELYGVEFDDDLDVDTVGGLLALELGRVPLPGAEVISHGLRLHAEGGTDHRGRVRIGTVLLSPAEPDGADDEEADHPG