Rv1815 Family assigned · low

H37Rv Rv1815 · MTBC0 mtbc0_001927 · 221 aa · 2075539–2076204 (+) · RefSeq NP_216331.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Protease-like fold (L5 protease, PDB 5MRT); putative peptidase.

Curated reference (UniProt)

UniProt P9WLR9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1815

UniProt still lists this protein as Uncharacterized protein Rv1815; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group29WEC
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005618, GO:0005623, 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 0.26 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 0.33% of strains (479) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 95.4 (very high). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
5mrt-assembly1_A 1.00 0.71 3.3e-08 sig 5mrt-assembly1_A Crystal structure of L5 protease Lysobacter sp. XL1
5mrt-assembly2_B 1.00 0.70 3.0e-08 sig 5mrt-assembly2_B Crystal structure of L5 protease Lysobacter sp. XL1
1gbi-assembly1_A 1.00 0.70 5.1e-08 sig 1gbi-assembly1_A ALPHA-LYTIC PROTEASE WITH MET 190 REPLACED BY ALA AND GLY 216 REPLACED BY LEU COMPLEX WITH METHOXYSUCCINYL-ALA-ALA-PRO-PHENYLALANINE BORONIC ACID
3urd-assembly1_A 1.00 0.70 5.7e-08 sig 3urd-assembly1_A T181A mutant of alpha-Lytic Protease
3lpr-assembly1_A 1.00 0.68 3.2e-08 sig 3lpr-assembly1_A STRUCTURAL BASIS FOR BROAD SPECIFICITY IN ALPHA-LYTIC PROTEASE MUTANTS
1hpg-assembly1_A 1.00 0.70 4.9e-08 sig 1hpg-assembly1_A A glutamic acid specific serine protease utilizes a novel histidine triad in substrate binding
5mrs-assembly2_B 1.00 0.68 4.1e-08 sig 5mrs-assembly2_B Crystal structure of L1 protease Lysobacter sp. XL1 in complex with AEBSF
1qrw-assembly1_A 1.00 0.67 4.1e-08 sig 1qrw-assembly1_A CRYSTAL STRUCTURE OF AN ALPHA-LYTIC PROTEASE MUTANT WITH ACCELERATED FOLDING KINETICS, R102H/G134S, PH 8

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

Closest characterised functional partner: Rv1816 (HTH-type transcriptional regulator), high confidence from genomic context alone (score 938 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1816 HTH-type transcriptional regulator 938 938 ctx neighborhood:700 coexpression:802
Rv1883c hyp hypothetical protein 798 798 coexpression:798
Rv1884c rpfC resuscitation-promoting factor RpfC 808 768 coexpression:765
Rv1814 erg3 membrane-bound C-5 sterol desaturase 745 745 ctx neighborhood:745
Rv3668c protease 510 42 textmining:510
Rv3036c TB22.2 hyp hypothetical protein 436 41 textmining:436

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

  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 5mrt-assembly1_A Crystal structure of L5 protease Lysobacter sp. XL1 (prob 1.00, E=3e-08, TM=0.71)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_216331.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 29WEC
  • Curated reference: UniProt P9WLR9 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 95.4, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 6 functional partner(s); context anchor Rv1816
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001927|Rv1815|
MVRLVPRAFAATVALLAAGFSPATASADPVLVFPGMEIRQDNHVCTLGYVDPALKIAFTAGHCRGGGAVTSRDYKVIGHLRAFRDNTPSGSTVATHELIADYEAIVLADDVTASNILPSGRALESRPGVVLHPGQAVCHFGVSTGETCGTVESVNNGWFTMSHGVLSEKGDSGGPVYLAPDGGPAQIVGIFNSVWGGFPAAVSWRSTSEQVHADLGVTPLA