Rv2843 Family assigned · low

H37Rv Rv2843 · MTBC0 mtbc0_003022 · 181 aa · 3170837–3171382 (+) · RefSeq NP_217359.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Small transmembrane protein, candidate subunit of the mycobacterial respiratory supercomplex (weak HHpred) RefSeq leaves this locus uncharacterised.

Curated reference (UniProt)

UniProt I6YAE2 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane alanine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2DYRJ

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 0 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 84.1 (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
8aav-assembly1_B 0.97 0.63 5.9e-01 8aav-assembly1_B Human heavy chain ferritin with introduced Cys residues modified with C10 ligand
8pp3-assembly1_B 0.94 0.63 8.1e-01 8pp3-assembly1_B Binary crystal structure of positively supercharged ferritin variant Ftn(pos) and crystal contact tuned negatively supercharged ferritin variant Ftn(neg)-m1 (Mg formate condition)
8pp3-assembly2_G 0.92 0.63 9.4e-01 8pp3-assembly2_G Binary crystal structure of positively supercharged ferritin variant Ftn(pos) and crystal contact tuned negatively supercharged ferritin variant Ftn(neg)-m1 (Mg formate condition)
8pp2-assembly1_D 0.91 0.57 5.9e-01 8pp2-assembly1_D Binary crystal structure of positively supercharged ferritin variant Ftn(pos) and native(K86Q) human heavy chain ferritin (Mg formate condition)
8pp2-assembly1_F 0.91 0.59 6.6e-01 8pp2-assembly1_F Binary crystal structure of positively supercharged ferritin variant Ftn(pos) and native(K86Q) human heavy chain ferritin (Mg formate condition)
6i9p-assembly1_A 0.91 0.59 8.1e-01 6i9p-assembly1_A Iron-free state of Rana catesbeiana H' ferritin variant H54N
8pp3-assembly2_I 0.89 0.63 1.2e+00 8pp3-assembly2_I Binary crystal structure of positively supercharged ferritin variant Ftn(pos) and crystal contact tuned negatively supercharged ferritin variant Ftn(neg)-m1 (Mg formate condition)
8pp5-assembly1_F 0.89 0.63 1.2e+00 8pp5-assembly1_F Unitary crystal structure of positively supercharged ferritin variant Ftn(pos)-m1 (Mg Formate condition)

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

Closest characterised functional partner: nusA (transcription termination/antitermination protein NusA), high confidence from genomic context alone (score 762 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2844 hyp hypothetical protein 913 913 ctx neighborhood:882
Rv3835 hyp hypothetical protein 772 773 ctx cooccurence:772
Rv3909 hyp hypothetical protein 770 770 ctx cooccurence:767
Rv2841c nusA transcription termination/antitermination protein NusA 762 762 ctx neighborhood:760
Rv2842c rimP ribosome maturation factor RimP 761 761 ctx neighborhood:760
Rv2164c hyp hypothetical protein 746 747 ctx cooccurence:743
Rv0538 membrane protein 743 744 ctx cooccurence:742
Rv1024 membrane protein 729 729 ctx cooccurence:725
Rv0007 membrane protein 719 720 ctx cooccurence:719
Rv1111c hyp hypothetical protein 708 709 ctx cooccurence:706
Rv1752 hyp hypothetical protein 697 698 ctx cooccurence:695
Rv0010c membrane protein 691 691 ctx cooccurence:691
Rv0339c iniR transcriptional regulator 683 684 ctx cooccurence:683
Rv1648 transmembrane protein 676 676 ctx cooccurence:675
Rv2739c transferase 664 665 ctx cooccurence:661

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

  • HHpred (Neff 7.28, weak, no significant E): best biological hit 7Q21_l Actinobacteria respiratory supercomplex 84% E1.8 (same complex as Rv0615/Rv1892); top hit a generic 4-helix-bundle of unknown function; DeepTMHMM TM; strong purifying
  • HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated function.

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_217359.1)
  • 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 2DYRJ
  • Curated reference: UniProt I6YAE2 (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 84.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 62 functional partner(s); context anchor nusA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003022|Rv2843|
MLRAAPVINRLTNRPISRRGVLAGGAALAALGVVSACGESAPKAPAVEELRSPLDQARHDGALAAAAATAIGIPPQVAAALTVVATQRTSHARALATEIARAAGKLVSATSETSSSSPSPTDPAAPPPAVSDVIDSLRTSAGEASRLVATTSGYRAGLLASIAASCTASYTVALVPSGPSI