Rv0613c Family assigned · medium auto-curated

H37Rv Rv0613c · MTBC0 mtbc0_000645 · 855 aa · 710500–713067 (-) · RefSeq NP_215127.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationSEC-C domain-containing protein
Revised (this work)SEC-C domain-containing protein. Pfam: SEC-C (PF02810.22).

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

Curated reference (UniProt)

UniProt I6Y897 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionSEC-C motif
Orthologous groupCOG3012

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 0.861 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 14 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (381) · 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
SEC-CPF02810.22 7.0e-09449–466 SEC-C motif

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

Closest characterised functional partner: iniB (isoniazid inducible protein IniB), high confidence from genomic context alone (score 775 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0341 iniB isoniazid inducible protein IniB 774 775 ctx cooccurence:773
Rv1004c membrane protein 789 773 ctx cooccurence:770
Rv0304c PPE5 PPE family protein PPE5 772 773 ctx cooccurence:772
Rv3350c PPE56 PPE family protein PPE56 772 772 ctx cooccurence:772
Rv0355c PPE8 PPE family protein PPE8 772 772 ctx cooccurence:772
Rv3347c PPE55 PPE family protein PPE55 772 772 ctx cooccurence:772
Rv2209 integral membrane protein 771 772 ctx cooccurence:771
Rv1917c PPE34 PPE family protein PPE34 771 772 ctx cooccurence:771
Rv3343c PPE54 PPE family protein PPE54 770 770 ctx cooccurence:770
Rv3879c espK ESX-1 secretion-associated protein EspK 769 769 ctx cooccurence:769
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 768 768 ctx cooccurence:768
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 767 767 ctx cooccurence:767
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 767 767 ctx cooccurence:767
Rv2954c hyp hypothetical protein 764 764 ctx cooccurence:762
Rv3864 espE ESX-1 secretion-associated protein EspE 762 762 ctx cooccurence:762

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: hypothetical protein
  • MTBC0 PGAP product: SEC-C domain-containing protein
  • Pfam (hmmscan --cut_ga): SEC-C PF02810.22 (E=7e-09)
  • (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_215127.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SEC-C (PF02810.22)
  • 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 COG3012
  • Curated reference: UniProt I6Y897 (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 — 113 functional partner(s); context anchor iniB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000645|Rv0613c|
MAEAFDATQAVARILAEHGPLSEDDIARRLLDSGVADPDAVLRALRLETEWPARQLVDDRWVWLPTLLAGRVFTHRLGADEAVHDMLGVTPDLDPITTLCEHEEYGRLADGSAARIVLAGYDEELLERRGIPDEAIDPGGALLLEPGTLATLGAAAGDLVGVRLTAAGLVLERIGTAGADTSVGARLAELVDPDEPAFFPAAVWTACVDDPAAFTEPVAPLREILDQHGLTHEDDWLAPGGFNFDAWRFENRCELLAFRHDLDPNDAVALYTLIKLHETMSLLLEATDPDELPRDVLATAAETATETGSDSLVDLLGDIGAALADPLLAELLVAETVGTDSGGAAALGLLTEMLEPKVPRAARVAVRWLRAVALDRIGDVEAAERELLAAESMDTEWPLPLLDLARIASDRGDAERGLALLRRAGTEPDHPLVRLLERHRAQPRRDLGRNEACWCGSGRKYKKCHLGREALPLAERVDWLYAKASQHALSGDWTGLLAEVSYERFRYADSDDEDALAAALADPLVLDAVLFEGGAFAEFLEVRGSLLPDDERLLAEQWLLVERSVFEVEHVQPGEGVIVRDVRTGDTHEVHERAASRQLRAGQLICARPVPAGDTMVFFGGIEPVALHERAVLIELLDDEPDPVTLVAQLSRRFAPPTLVNTEGDSLAICEASVRVDDPAGIQGALDGVYDRVDGEEPPRWIEHVTNDGMLRVRATLVLDGDTLRVETNSEPRMDRVLATLTRLDPAMTVLDDDRRPLRNTREAAALAEQMPVTGAGAPDPDSPELAAALEEFIRDYETSWLDQPIPALDGHTPRQAADDPTRRADLIKLLDTFPAGAGARGGMDADRLRTALGL