Rv2360c Still unknown · low

H37Rv Rv2360c · MTBC0 mtbc0_002512 · 142 aa · 2666343–2666771 (-) · RefSeq NP_216876.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical; function unknown. Structure-based hint rejected: non-transferable fold (Deinococcus DR_1245 chaperone); function unknown.

Curated reference (UniProt)

UniProt O05838 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)

Orthologous group2CA90

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 0.092 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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)

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 82.8 (confident). 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
4h5b-assembly1_A 0.99 0.52 1.6e-02 4h5b-assembly1_A Crystal Structure of DR_1245 from Deinococcus radiodurans
3ule-assembly1_D 0.23 0.26 1.0e-01 3ule-assembly1_D Structure of Bos taurus Arp2/3 complex with bound inhibitor CK-869 and ATP
4usi-assembly1_A 0.21 0.34 3.2e-01 4usi-assembly1_A Nitrogen regulatory protein PII from Chlamydomonas reinhardtii in complex with MgATP and 2-oxoglutarate
1fr5-assembly1_A 0.21 0.34 3.5e-01 1fr5-assembly1_A PHAGE FR CAPSIDS WITH A FOUR RESIDUE DELETION IN THE COAT PROTEIN FG LOOP
6dec-assembly1_D 0.21 0.29 2.4e-01 6dec-assembly1_D Crystal structure of Bos taurus Arp2/3 complex binding with C-terminus of Homo sapiens SPIN90
6yw7-assembly1_D 0.16 0.23 1.6e-01 6yw7-assembly1_D Cryo-EM structure of the ARP2/3 1A5C isoform complex.
1hwu-assembly3_B 0.14 0.39 1.1e+00 1hwu-assembly3_B STRUCTURE OF PII PROTEIN FROM HERBASPIRILLUM SEROPEDICAE
6ser-assembly1_A 0.12 0.29 3.0e-01 6ser-assembly1_A Crystal structure of human STARD10

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

Closest characterised functional partner: uppS (decaprenyl diphosphate synthase), high confidence from genomic context alone (score 904 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2361c uppS decaprenyl diphosphate synthase 937 904 ctx neighborhood:882
Rv2362c recO DNA repair protein RecO 902 887 ctx neighborhood:882
Rv2363 amiA2 amidase 786 786 ctx neighborhood:786
Rv0556 transmembrane protein 768 768 ctx cooccurence:761
Rv3212 hyp hypothetical protein 767 767 ctx cooccurence:764
Rv0497 transmembrane protein 766 767 ctx cooccurence:766
Rv2732c transmembrane protein 762 762 ctx cooccurence:761
Rv1486c hyp hypothetical protein 760 760 ctx cooccurence:758
Rv1109c hyp hypothetical protein 758 758 ctx cooccurence:757
Rv0383c ttfA hyp hypothetical protein 752 752 ctx cooccurence:752
Rv0863 hyp hypothetical protein 750 751 ctx cooccurence:749
Rv0475 hbhA heparin binding hemagglutinin HbhA 750 750 ctx cooccurence:750
Rv2138 lppL lipoprotein LppL 741 742 ctx cooccurence:740
Rv0775 hyp hypothetical protein 737 737 ctx cooccurence:734
Rv2091c membrane protein 735 735 ctx cooccurence:734

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

  • Structural Foldseek hit not propagated -- non-transferable fold (Deinococcus DR_1245 chaperone); function unknown
  • Reviewed against literature (extended structural cross-check, 2026-06-02)

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_216876.1)
  • 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 2CA90
  • Curated reference: UniProt O05838 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 82.8, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 95 functional partner(s); context anchor uppS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002512|Rv2360c|
MPSLPDRLASILRDVLPAEEEPDGALTVRHDGTFASLRVVSIAEDLELVSLTQILAWDLPLTKRLTEQVAKQARDINFGSVSLREKVSEKAARRSSGRPASNTADVMLRYNFPGTGLTDDALRTLILLVLETGATIRSALVG