Rv2100 Still unknown · low auto-curated

H37Rv Rv2100 · MTBC0 - · 550 aa · 2358389–2360041 (+) · RefSeq NP_216616.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WLJ3 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized protein Rv2100

UniProt still lists this protein as Uncharacterized protein Rv2100; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
eggNOG descriptionHNH endonuclease
Orthologous groupCOG1403
Gene Ontology (8) GO:0005575, 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 0.598 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 10 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (174) · 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
DUF222PF02720.23 3.2e-5366–321 Domain of unknown function (DUF222)

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

Closest characterised functional partner: PE_PGRS36 (PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub), medium confidence from genomic context alone (score 646 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3074 hyp hypothetical protein 927 800 coexpression:730 textmining:652
Rv3776 hyp hypothetical protein 801 800 coexpression:798
Rv1765c hyp hypothetical protein 771 771 ctx cooccurence:759
Rv2015c hyp hypothetical protein 769 770 ctx cooccurence:761
Rv0094c hyp hypothetical protein 732 733 ctx cooccurence:677
Rv1148c hyp hypothetical protein 942 717 ctx cooccurence:680 textmining:805
Rv3467 hyp hypothetical protein 706 707 ctx cooccurence:677
Rv1587c hyp hypothetical protein 703 704 ctx cooccurence:695
Rv1945 hyp hypothetical protein 939 701 ctx cooccurence:684 textmining:805
Rv1128c hyp hypothetical protein 936 686 ctx cooccurence:681 textmining:805
Rv1073 hyp hypothetical protein 651 651 ctx cooccurence:647
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 646 646 ctx neighborhood:505
Rv0756c hyp hypothetical protein 604 605 ctx cooccurence:599
Rv1157c hyp hypothetical protein 595 595 ctx cooccurence:593
Rv2721c hyp hypothetical protein 591 591 ctx cooccurence:591

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=3e-53)
  • (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_216616.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
  • 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 COG1403
  • Curated reference: UniProt P9WLJ3 (SwissProt, reviewed; Inferred from homology)
  • 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 — 56 functional partner(s); context anchor PE_PGRS36
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2100|
MAGALFEPSFAAAHPAGLLRRPVTRTVVLSVAATSIAHMFEISLPDPTELCRSDDGALVAAIEDCARVEAAASARRLSAIAELTGRRTGADQRADWACDFWDCAAAEVAAALTISHGKASGQMHLSLALNRLPQVAALFLAGHLGARLFSIIAWRTYLVRDPHALSLLDAALAEHAGAWGPLSAPKLEKAIDSWIDRYDPGALRRSRISARTRDLCIGDPDEDAGTAALWGRLYATDAAMLDRRLTEMAHGVCEDDPRTLAQRRADALGALAAGADHLACGCGKPDCPSGAGNDERAAGVVIHVVADASALDAQPDPHLSGDEPPSRPLTPETTLFEALTPDPEPDPPATHAPAELITTGGGVVPAPLLAELIRGGATISQVRHPGDLAAEPHYRPSAKLAEFVRMRDLTCRFPGCDVPAEFCDIDHSAPWPLGPTHPSNLKCACRKHHLLKTFWTGWRDVQLPDGTVIWTAPNGHTYTTHPGSRIFFPTWHTTTAELPQTSTAAVNVDARGLMMPRRRRTRAAELAHRINAERALNDAYMAERNKPPSF