Rv2473 Still unknown · low auto-curated

H37Rv Rv2473 · MTBC0 mtbc0_002635 · 238 aa · 2799816–2800532 (+) · RefSeq NP_216989.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 5xsj-assembly1_L XylFII-LytSN complex (prob 0.97, TM 0.45).

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

Curated reference (UniProt)

UniProt O53200 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible alanine and proline rich membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2ATIH

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 0.94 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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 83.1 (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
5xsj-assembly1_L 0.97 0.45 8.7e-02 5xsj-assembly1_L XylFII-LytSN complex
1y4c-assembly1_A 0.97 0.56 2.7e-01 1y4c-assembly1_A Designed Helical Protein fusion MBP
5jsn-assembly2_D 0.54 0.43 6.7e-01 5jsn-assembly2_D Bcl2-inhibitor complex
8eup-assembly1_b 0.41 0.50 1.9e+00 8eup-assembly1_b Ytm1 associated 60S nascent ribosome State 1A
1xzp-assembly1_A 0.35 0.55 2.1e+00 1xzp-assembly1_A Structure of the GTP-binding protein TrmE from Thermotoga maritima
7xgf-assembly2_D 0.33 0.40 1.4e+00 7xgf-assembly2_D Crystal structure of BCL-xL in complex with computationally designed inhibitor protein
8eja-assembly1_B 0.28 0.40 1.3e+00 8eja-assembly1_B Computational design of potent and selective inhibitors of Bak and Bax
3fyq-assembly1_A 0.20 0.36 1.4e+00 3fyq-assembly1_A Structure of Drosophila melanogaster talin IBS2 domain (residues 1981-2168)

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

Closest characterised functional partner: aglA (alpha-glucosidase AglA), medium confidence from genomic context alone (score 586 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2472 hyp hypothetical protein 786 786 ctx neighborhood:781
Rv2471 aglA alpha-glucosidase AglA 585 586 ctx neighborhood:586
Rv2470 glbO hemoglobin GlbO 577 578 ctx neighborhood:578
Rv2469c hyp hypothetical protein 412 413 ctx neighborhood:407

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

  • Legacy H37Rv annotation: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 5xsj-assembly1_L XylFII-LytSN complex (prob 0.97, E=9e-02, TM=0.45)
  • (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_216989.1)
  • 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 2ATIH
  • Curated reference: UniProt O53200 (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 83.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 4 functional partner(s); context anchor aglA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002635|Rv2473|
MAPTSSSVASELLMPWPSAAASGVVGWRTTATASQRYHRPMSDTPFAEPYPEQRPPWGVPPPGWDGSSRPAPSTTPRSPGRWSLVAALALAVVSLGVGIVGWFHRQPHDKPSPAPSAPTFTSQQISDAKENVCAAHRIVRQAAVLNTNQANPVPGDPTGDLAVAANARLALYSGGDYLLRRLTAEPATPAELRDAVRSLANALQELAVNYLAGAPDSVVTPLRLALERDTRAVDPLCV