Rv3395c Family assigned · medium auto-curated

H37Rv Rv3395c · MTBC0 mtbc0_003607 · 204 aa · 3836461–3837075 (-) · RefSeq NP_217912.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Contains MT3502_N (PF27531.1), Rv3395c_C (PF27314.1) domain(s); putative function inferred from the domain architecture.

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

Curated reference (UniProt)

UniProt P9WKZ9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv3395c

UniProt still lists this protein as Uncharacterized protein Rv3395c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionComponent of the SOS system and an inhibitor of cell division. Accumulation of SulA causes rapid cessation of cell division and the appearance of long, non-septate filaments. In the presence of GTP, binds a polymerization-competent form of FtsZ in a 1 1 ratio, thus inhibiting FtsZ polymerization and therefore preventing it from participating in the assembly of the Z ring. This mechanism prevents the premature segregation of damaged DNA to daughter cells during cell division
Orthologous groupCOG4544
Gene Ontology (22) GO:0006139, GO:0006259, GO:0006281, GO:0006725, GO:0006807, GO:0006950, GO:0006974, GO:0008150, GO:0008152, GO:0009987, GO:0033554, GO:0034641 +10 more

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 1.232 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
MT3502_NPF27531.1 4.6e-3649–163 MT3502 N-terminal domain
Rv3395c_CPF27314.1 8.7e-19166–204 Rv3395c C-terminal domain

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

Closest characterised functional partner: dnaE2 (error-prone DNA polymerase), high confidence from genomic context alone (score 879 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3394c hyp hypothetical protein 999 998 ctx neighborhood:882 cooccurence:772 coexpression:936 textmining:661
Rv3370c dnaE2 error-prone DNA polymerase 958 879 ctx cooccurence:762 coexpression:432 textmining:671
Rv1537 dinX DNA polymerase IV 761 704 coexpression:693
Rv3056 dinP DNA polymerase IV 2 730 701 coexpression:690
Rv3395A membrane protein 948 617 ctx neighborhood:615 textmining:870
Rv3396c guaA GMP synthase 546 546 ctx neighborhood:544
Rv0513 transmembrane protein 507 507 ctx cooccurence:500
Rv1547 dnaE1 DNA polymerase III subunit alpha 522 444 coexpression:412
Rv1249c membrane protein 427 427 ctx cooccurence:409
Rv2560 hyp hypothetical protein 418 418 ctx cooccurence:418
Rv3196 hyp hypothetical protein 415 415 ctx cooccurence:413
Rv1696 recN DNA repair protein RecN 559 410 coexpression:410
Rv3776 hyp hypothetical protein 513 410
Rv2100 hyp hypothetical protein 879 409 textmining:804
Rv0784 hyp hypothetical protein 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: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Pfam (hmmscan --cut_ga): MT3502_N PF27531.1 (E=5e-36), Rv3395c_C PF27314.1 (E=9e-19)
  • (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_217912.2)
  • Domains: Pfam-A via hmmscan --cut_ga — MT3502_N (PF27531.1), Rv3395c_C (PF27314.1)
  • 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 COG4544
  • Curated reference: UniProt P9WKZ9 (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 — 29 functional partner(s); context anchor dnaE2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003607|Rv3395c|
MTVAFASDQRLENGAEQLESLRRQMALLSEKVSGGPSRSGDLVPAGPVSLPPGTVGVLSGARSLLLSMVASVTAAGGNAAIVGQPDIGLLAAVEMGADLSRLAVIPDPGTDPVEVAAVLIDGMDLVVLGLGGRRVTRARARAVVARARQKGCTLLVTDGDWQGVSTRLAARVCGYEITPALRGVPTPGLGRISGVRLQINGRGR