Rv1443c Family assigned · low auto-curated · to review

H37Rv Rv1443c · MTBC0 - · 161 aa · 1622207–1622692 (-) · RefSeq NP_215959.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 1z94-assembly1_A X-Ray Crystal Structure of Protein CV1439 from Chromobacterium (prob 1.00, TM 0.76). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

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 O06816 TrEMBL · unreviewed · Evidence at protein level
UniProt nameLigand-binding SRPBCC domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPfam Polyketide cyclase dehydrase and lipid transport
Orthologous groupCOG4276

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 0.68 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
DUF8410PF28469.1 5.6e-6114–158 Domain of unknown function (DUF8410)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 88.0 (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
1z94-assembly1_A 1.00 0.76 5.2e-08 sig 1z94-assembly1_A X-Ray Crystal Structure of Protein CV1439 from Chromobacterium violaceum. Northeast Structural Genomics Consortium Target CvR12.
7wa9-assembly1_A 1.00 0.79 3.9e-07 sig 7wa9-assembly1_A Crystal structure of MSMEG_5634 from Mycobacterium smegmatis
5z8o-assembly1_A 1.00 0.77 3.6e-07 sig 5z8o-assembly1_A Structural of START superfamily protein MSMEG_0129 from Mycobacterium smegmatis
2ns9-assembly1_B 1.00 0.66 7.9e-08 sig 2ns9-assembly1_B Crystal structure of protein APE2225 from Aeropyrum pernix K1, Pfam COXG
8ho2-assembly1_B 1.00 0.67 2.9e-07 sig 8ho2-assembly1_B crystal structure of Norcoclaurine synthase from Chinese lotus (Nelumbo nucicera)
1z94-assembly2_E-2 1.00 0.71 3.6e-07 sig 1z94-assembly2_E-2 X-Ray Crystal Structure of Protein CV1439 from Chromobacterium violaceum. Northeast Structural Genomics Consortium Target CvR12.
4a8v-assembly1_A 1.00 0.65 7.8e-07 sig 4a8v-assembly1_A Crystal Structure of Birch Pollen Allergen Bet v 1 isoform j in complex with 8-Anilinonaphthalene-1-sulfonate (ANS)
2vq5-assembly1_A-2 1.00 0.62 4.3e-07 sig 2vq5-assembly1_A-2 X-ray structure of Norcoclaurine synthase from Thalictrum flavum in complex with dopamine and hydroxybenzaldehyde

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

Closest characterised functional partner: lppF (lipoprotein LppF), medium confidence from genomic context alone (score 674 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3594 hyp hypothetical protein 675 675 ctx cooccurence:675
Rv1921c lppF lipoprotein LppF 674 674 ctx cooccurence:674
Rv1754c hyp hypothetical protein 510 510 ctx cooccurence:510
Rv1541c lprI lipoprotein LprI 504 504 ctx cooccurence:504
Rv3879c espK ESX-1 secretion-associated protein EspK 481 481 ctx cooccurence:481
Rv3882c eccE1 ESX-1 secretion system protein EccE1 468 468 ctx cooccurence:468
Rv3875 esxA ESAT-6 protein EsxA 453 453 ctx cooccurence:450
Rv1978 hyp hypothetical protein 450 450 ctx cooccurence:450
Rv1288 hyp hypothetical protein 429 430 ctx cooccurence:428
Rv0097 oxidoreductase 425 425 ctx cooccurence:425
Rv3877 eccD1 ESX-1 secretion system protein EccD1 421 422 ctx cooccurence:420

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): DUF8410 PF28469.1 (E=6e-61)
  • Foldseek best: 1z94-assembly1_A X-Ray Crystal Structure of Protein CV1439 from Chromobacterium (prob 1.00, E=5e-08, TM=0.76)
  • (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_215959.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF8410 (PF28469.1)
  • 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 COG4276
  • Curated reference: UniProt O06816 (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 88.0, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 11 functional partner(s); context anchor lppF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1443c|
MVGYAEPVLIERQSVVAAPAEQVWQRVVTPEGINDELRPWMTMSVPRGAKGMTVDTVPIGAPIGRAWLRLFGVLPFDYDRLSIAELEPGRRFREDSTMLSMRQWQHERTVTPEGDTKTIVRDRITFQTRAGLRFAAPLIAAGLRALFGHRHRRLQRHFAQG