Rv0481c Family assigned · low

H37Rv Rv0481c · MTBC0 mtbc0_000506 · 174 aa · 573353–573877 (-) · RefSeq NP_214995.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2505 domain-containing protein
Revised (this work)DUF2505; ESMFold matches a START-like / Ups1 lipid-transfer fold (PDB 5JQM); putative lipid-binding protein.

Curated reference (UniProt)

UniProt P9WKV5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0481c

UniProt still lists this protein as Uncharacterized protein Rv0481c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2505)
Orthologous group2ED3C

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 3 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
DUF2505PF10698.16 1.7e-457–170 Protein of unknown function (DUF2505)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 95.8 (very high). 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
5jqm-assembly1_B 1.00 0.66 2.4e-07 sig 5jqm-assembly1_B Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 Void of Bound Phospholipid from Saccharomyces Cerevisiae at 1.5 Angstroms Resolution
8ag0-assembly1_A 1.00 0.63 1.0e-07 sig 8ag0-assembly1_A Crystal structure of mutant PRELID3a-TRIAP1 complex - R53E
2d4r-assembly1_A 1.00 0.69 3.7e-07 sig 2d4r-assembly1_A Crystal structure of TTHA0849 from Thermus thermophilus HB8
6cay-assembly1_A 1.00 0.76 4.5e-06 sig 6cay-assembly1_A Crystal structure of the first StART-like domain of Ysp2p/Lam2p in its apo and ergosterol-bound state.
5jqm-assembly1_C 1.00 0.64 8.3e-07 sig 5jqm-assembly1_C Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 Void of Bound Phospholipid from Saccharomyces Cerevisiae at 1.5 Angstroms Resolution
5jqm-assembly1_A 1.00 0.65 1.8e-06 sig 5jqm-assembly1_A Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 Void of Bound Phospholipid from Saccharomyces Cerevisiae at 1.5 Angstroms Resolution
6byd-assembly1_A 1.00 0.76 6.0e-05 sig 6byd-assembly1_A Crystal structure of the second StART domain of yeast Lam4
6v8j-assembly4_D 1.00 0.60 2.0e-06 sig 6v8j-assembly4_D Crystal structure of Ara h 8.0201

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

Closest characterised functional partner: Rv0479c (membrane protein), high confidence from genomic context alone (score 877 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0479c membrane protein 876 877 ctx neighborhood:741 cooccurence:544
Rv0483 lprQ lipoprotein LprQ 809 809 ctx neighborhood:734
Rv0482 murB UDP-N-acetylenolpyruvoylglucosamine reductase 792 792 ctx neighborhood:790
Rv0996 transmembrane protein 767 768 ctx cooccurence:767
Rv0556 transmembrane protein 764 765 ctx cooccurence:764
Rv1109c hyp hypothetical protein 764 765 ctx cooccurence:764
Rv3212 hyp hypothetical protein 760 761 ctx cooccurence:754
Rv2091c membrane protein 750 750 ctx cooccurence:750
Rv2446c integral membrane protein 747 747 ctx cooccurence:747
Rv0480c amidohydrolase 744 745 ctx neighborhood:741
Rv0475 hbhA heparin binding hemagglutinin HbhA 743 743 ctx cooccurence:741
Rv3850 hyp hypothetical protein 742 743 ctx cooccurence:741
Rv3438 hyp hypothetical protein 741 742 ctx cooccurence:740
Rv0358 hyp hypothetical protein 739 739 ctx cooccurence:738
Rv0863 hyp hypothetical protein 735 735 ctx cooccurence:735

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

  • MTBC0 PGAP product: DUF2505 domain-containing protein
  • Pfam: DUF2505 PF10698.16
  • Foldseek best: 5jqm-assembly1_B Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 V (prob 1.00, E=2e-07, TM=0.66)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_214995.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2505 (PF10698.16)
  • 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 2ED3C
  • Curated reference: UniProt P9WKV5 (SwissProt, reviewed; 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 95.8, very high)
  • 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 Rv0479c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000506|Rv0481c|
MPRSFDMSADYEGSVEEVHRAFYEADYWKARLAETPVDVATLESIRVGGDSGDDGTIEVVTLQMVRSHNLPGLVTQLHRGDLSVRREETWGPVKEGIATASIAGSIVDAPVNLWGTAVLSPIPESGGSRMTLQVTIQVRIPFIGGKLERLIGTQLSQLVTIEQRFTTLWITNNV