Rv3835 Family assigned · medium auto-curated

H37Rv Rv3835 · MTBC0 mtbc0_004064 · 449 aa · 4333157–4334506 (+) · RefSeq NP_218352.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationseptum formation family protein
Revised (this work)Septum formation family protein. Pfam: Septum_form (PF13845.12).

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

Curated reference (UniProt)

UniProt P9WKW5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized membrane protein Rv3835
Curated functionMay play a role in septum formation.

UniProt still lists this protein as Uncharacterized membrane protein Rv3835; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionSeptum formation
Orthologous group2BXNT
Gene Ontology (9) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 1.766 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.33% of strains (472) · 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
Septum_formPF13845.12 2.2e-7998–322 Septum formation

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

Closest characterised functional partner: serS (serine--tRNA ligase), high confidence from genomic context alone (score 776 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3836 hyp hypothetical protein 885 885 ctx neighborhood:882
Rv3909 hyp hypothetical protein 776 776 ctx cooccurence:774
Rv3834c serS serine--tRNA ligase 775 776 ctx neighborhood:775
Rv2843 hyp hypothetical protein 772 773 ctx cooccurence:772
Rv2164c hyp hypothetical protein 923 770 ctx cooccurence:766 textmining:680
Rv1024 membrane protein 767 768 ctx cooccurence:761
Rv1111c hyp hypothetical protein 766 766 ctx cooccurence:756
Rv0538 membrane protein 752 753 ctx cooccurence:749
Rv2709 transmembrane protein 749 749 ctx cooccurence:741
Rv3494c mce4F Mce family protein Mce4 749 749 ctx cooccurence:744
Rv0339c iniR transcriptional regulator 745 746 ctx cooccurence:739
Rv3658c transmembrane protein 725 725 ctx cooccurence:722
Rv0007 membrane protein 722 722 ctx cooccurence:719
Rv2264c hyp hypothetical protein 726 716 ctx cooccurence:712
Rv2732c transmembrane protein 707 708 ctx cooccurence:706

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: septum formation family protein
  • Pfam (hmmscan --cut_ga): Septum_form PF13845.12 (E=2e-79)
  • (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_218352.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Septum_form (PF13845.12)
  • 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 2BXNT
  • Curated reference: UniProt P9WKW5 (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 — 97 functional partner(s); context anchor serS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004064|Rv3835|
MLDAPEQDPVDPGDPASPPHGEAEQPLPGPRWPRALRASATRRALLLTALGGLLIAGLVTAIPAVGRAPERLAGYIASNPVPSTGAKINASFNRVASGDCLMWPDGTPESAAIVSCADEHRFEVAESIDMRTFPGMEYGQNAAPPSPARIQQISEEQCEAAVRRYLGTKFDPNSKFTISMLWPGDRAWRQAGERRMLCGLQSPGPNNQQLAFKGKVADIDQSKVWPAGTCLGIDATTNQPIDVPVDCAAPHAMEVSGTVNLAERFPDALPSEPEQDGFIKDACTRMTDAYLAPLKLRTTTLTLIYPTLTLPSWSAGSRVVACSIGATLGNGGWATLVNSAKGALLINGQPPVPPPDIPEERLNLPPIPLQLPTPRPAPPAQQLPSTPPGTQHLPAQQPVVTPTRPPESHAPASAAPAETQPPPPDAGAPPATQSPEATPPGPAEPAPAG