Rv0966c Still unknown · low

H37Rv Rv0966c · MTBC0 mtbc0_001032 · 200 aa · 1084448–1085050 (-) · RefSeq NP_215481.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF1707 domain-containing protein
Revised (this work)DUF1707; Foldseek hits non-conclusive (moderate TM). Function unknown.

Curated reference (UniProt)

UniProt P9WKM1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0966c

UniProt still lists this protein as Uncharacterized protein Rv0966c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF1707)
Orthologous groupCOG4758
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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) pseudogene candidate

pN/pS 0.359 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 17.56% of strains (25502) · clonal

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
DUF1707PF08044.17 9.1e-1618–69 DUF1707 SHOCT-like domain

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 87.3 (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
4qrk-assembly1_A 1.00 0.57 9.5e-03 sig 4qrk-assembly1_A Crystal structure of a putative cell adhesion protein (CLOSPO_03726) from Clostridium sporogenes ATCC 15579 at 1.95 A resolution
3tv2-assembly1_A 0.07 0.39 6.7e+00 3tv2-assembly1_A Structure of a class II fumarate hydratase from Burkholderia pseudomallei
3rrp-assembly1_A 0.05 0.38 9.2e+00 3rrp-assembly1_A Crystal structure of fumarate hydratase Fum from Mycobacterium abscessus with malate bound
3uyu-assembly1_A 0.03 0.20 2.3e+00 3uyu-assembly1_A Structural basis for the antifreeze activity of an ice-binding protein (LeIBP) from Arctic yeast
7dc5-assembly2_B 0.00 0.12 7.9e+00 7dc5-assembly2_B Crystal structure of fungal antifreeze protein with intermediate activity

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

Closest characterised functional partner: csoR (copper-sensing transcriptional repressor CsoR), medium confidence from genomic context alone (score 578 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0965c hyp hypothetical protein 718 718 ctx neighborhood:711
Rv0967 csoR copper-sensing transcriptional repressor CsoR 578 578 ctx neighborhood:574
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 569 569 coexpression:426
Rv2027c dosT two component sensor histidine kinase DosT 520 500 coexpression:483
Rv0845 narS sensor histidine kinase NarS 519 499 coexpression:482
Rv3132c devS two component sensor histidine kinase DevS 517 497 coexpression:480
Rv0964c hyp hypothetical protein 490 490 ctx neighborhood:488
Rv0412c glnX membrane protein 479 479 ctx cooccurence:466
Rv0971c echA7 enoyl-CoA hydratase EchA7 457 458 ctx neighborhood:455
Rv0973c accA2 acetyl/propionyl-CoA carboxylase subuit alpha 455 456 ctx neighborhood:454
Rv1638A hyp hypothetical protein 484 455 coexpression:436
Rv0974c accD2 acetyl-/propionyl-CoA carboxylase subunit beta 453 453 ctx neighborhood:453
Rv2744c 35kd_ag hyp hypothetical protein 478 449 coexpression:430
Rv0968 hyp hypothetical protein 448 448 ctx neighborhood:448
Rv1337 integral membrane protein 443 443 ctx cooccurence:436

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: DUF1707 domain-containing protein
  • Pfam: DUF1707 PF08044.17
  • Foldseek best: 4qrk-assembly1_A Crystal structure of a putative cell adhesion protein (CLOSPO_0 (prob 1.00, E=1e-02, TM=0.57)
  • (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_215481.2)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF1707 (PF08044.17)
  • 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 COG4758
  • Curated reference: UniProt P9WKM1 (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 87.3, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 33 functional partner(s); context anchor csoR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001032|Rv0966c|
MSNSAQRDARNSRDESARASDTDRIQIAQLLAYAAEQGRLQLTDYEDRLARAYAATTYQELDRLRADLPGAAIGPRRGGECNPAPSTLLLALLGGFERRGRWNVPKKLTTFTLWGSGVLDLRYADFTSTEVDIRAYSIMGAQTILLPPEVNVEIHGHRVMGGFDRKVVGEGTRGAPTVRIRGFSLWGDVGIKRKPRKPRK