Rv2683 Family assigned · medium auto-curated

H37Rv Rv2683 · MTBC0 - · 165 aa · 3000112–3000609 (+) · RefSeq NP_217199.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains CBS (PF00571.34) 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.

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 I6X540 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionCBS domain
Orthologous groupCOG0517

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 1.413 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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
CBSPF00571.34 5.0e-05116–162 CBS domain

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

Closest characterised functional partner: arsA (arsenic-transport integral membrane protein ArsA), high confidence from genomic context alone (score 950 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2684 arsA arsenic-transport integral membrane protein ArsA 950 950 ctx neighborhood:801 cooccurence:723
Rv2685 arsB1 arsenic-transport integral membrane protein ArsB 898 899 ctx neighborhood:606 cooccurence:728
Rv3396c guaA GMP synthase 906 799 coexpression:649 textmining:554
Rv2299c htpG chaperone protein HtpG 757 725 database:659
Rv1733c transmembrane protein 695 696 ctx cooccurence:695
Rv2682c dxs1 1-deoxy-D-xylulose 5-phosphate synthase 644 645 ctx neighborhood:645
Rv0018c pstP phosphoserine/threonine phosphatase PstP 654 637 database:626
Rv3887c eccD2 ESX-2 secretion system protein EccD 585 585 ctx cooccurence:584
Rv0462 lpdC dihydrolipoamide dehydrogenase 583 583 experimental:409
Rv3303c lpdA NAD(P)H quinone reductase LpdA 582 582 experimental:409
Rv2855 mtr mycothione reductase 581 582 experimental:409
Rv0794c oxidoreductase 581 581 experimental:409
Rv2713 sthA pyridine nucleotide transhydrogenase 581 581 experimental:409
Rv2390c hyp hypothetical protein 572 572 ctx cooccurence:476
Rv0853c pdc alpha-keto-acid decarboxylase 512 512 coexpression:453

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): CBS PF00571.34 (E=5e-05)
  • (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_217199.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CBS (PF00571.34)
  • 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 COG0517
  • Curated reference: UniProt I6X540 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 48 functional partner(s); context anchor arsA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2683|
MKVNIDPTAPTFATYRRDMRAEQMAEDYPVVSIDSDALDAARMLAEHRLPGLLVTAGAGKQYAVLPASQVVRFIVPRYVQDDPLLAGVLNESTADRCAERLSGKKVRDVLPDHLVEVPPANADDTIIEVAAVMARLRSPLLAVVKDGSLLGVVTASRLLAAALKT