Rv0875c Still unknown · low auto-curated

H37Rv Rv0875c · MTBC0 mtbc0_000930 · 162 aa · 977018–977506 (-) · RefSeq NP_215390.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2771 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2771. Function unknown. Foldseek best (non-significant) hit: 6d0k-assembly1_D Crystal structure of a CLC-type fluoride/proton antip (prob 0.60, 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 P9WKR7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0875c

UniProt still lists this protein as Uncharacterized protein Rv0875c; 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 (DUF2771)
Orthologous group2EMAJ
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.091 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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
DUF2771PF10969.14 8.9e-4532–159 Protein of unknown function (DUF2771)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 95.6 (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
6d0k-assembly1_D 0.60 0.45 1.8e-01 6d0k-assembly1_D Crystal structure of a CLC-type fluoride/proton antiporter, E118Q mutant
6fy3-assembly1_X 0.54 0.37 1.3e-01 6fy3-assembly1_X Crystal structure of a V2-directed, RV144 vaccine-like antibody from HIV-1 infection, CAP228-3D, bound to a heterologous V2 peptide
7t0r-assembly2_I 0.38 0.41 4.2e-01 7t0r-assembly2_I Crystal structure of the anti-CD4 adnectin 6940_B01 as a complex with the extracellular domains of CD4 and ibalizumab fAb
5j7c-assembly1_C 0.35 0.46 6.9e-01 5j7c-assembly1_C A picomolar affinity FN3 domain in complex with hen egg-white lysozyme
7t0o-assembly1_Q 0.33 0.34 1.9e-01 7t0o-assembly1_Q cryoEM reconstruction of the HIV gp140 in complex with the extracellular domains of CD4 and the adnectin domain of Combinectin. The gp140 and CD4 coordinates from entry 6EDU were rigid body fitted to the EM map along withe the crystal structure of CD4+adnectin
6c83-assembly1_C 0.28 0.39 3.6e-01 6c83-assembly1_C Structure of Aurora A (122-403) bound to inhibitory Monobody Mb2 and AMPPCP
4lsd-assembly3_H 0.21 0.39 5.5e-01 4lsd-assembly3_H Myokine structure
9jqt-assembly1_A 0.18 0.28 1.7e-01 9jqt-assembly1_A Structure of interleukin receptor common gamma chain (IL2Rgamma/CD132) in complex with 2D4

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

Closest characterised functional partner: Rv0876c (transmembrane protein), high confidence from genomic context alone (score 968 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0876c transmembrane protein 968 968 ctx neighborhood:882 coexpression:740
Rv0877 hyp hypothetical protein 884 884 ctx neighborhood:774 cooccurence:506
Rv1171 hyp hypothetical protein 771 771 ctx cooccurence:770
Rv0048c membrane protein 756 756 ctx cooccurence:756
Rv3779 transmembrane protein 745 745 ctx cooccurence:743
Rv0902c prrB two component sensor histidine kinase PrrB 740 740 coexpression:740
Rv1353c HTH-type transcriptional regulator 730 731 ctx cooccurence:729
Rv2079 hyp hypothetical protein 705 706 ctx cooccurence:705
Rv0275c transcriptional regulator 703 703 ctx cooccurence:701
Rv3202c adnA ATP-dependent DNA helicase 700 701 ctx cooccurence:699
Rv3166c hyp hypothetical protein 689 690 ctx cooccurence:688
Rv1635c mannosyltransferase 654 654 ctx cooccurence:649
Rv0822c hyp hypothetical protein 633 633 ctx cooccurence:628
Rv2423 hyp hypothetical protein 629 629 ctx cooccurence:629
Rv1363c membrane protein 628 628 ctx cooccurence:627

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: DUF2771 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2771 PF10969.14 (E=9e-45)
  • Foldseek best: 6d0k-assembly1_D Crystal structure of a CLC-type fluoride/proton antiporter, E11 (prob 0.60, E=2e-01, 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_215390.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2771 (PF10969.14)
  • 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 2EMAJ
  • Curated reference: UniProt P9WKR7 (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 95.6, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 63 functional partner(s); context anchor Rv0876c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000930|Rv0875c|
MKRGVATLPVILVILLSVAAGAGAWLLVRGHGPQQPEISAYSHGHLTRVGPYLYCNVVDLDDCQTPQAQGELPVSERYPVQLSVPEVISRAPWRLLQVYQDPANTTSTLFRPDTRLAVTIPTVDPQRGRLTGIVVQLLTLVVDHSGELRDVPHAEWSVRLIF