Rv1961 Still unknown · low auto-curated

H37Rv Rv1961 · MTBC0 mtbc0_002076 · 164 aa · 2223328–2223822 (+) · RefSeq NP_216477.1

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: 5umr-assembly1_A Crystal structure of N-terminal domain of human FACT (prob 0.33, TM 0.74).

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

Curated reference (UniProt)

UniProt P95253 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionhelicase
Orthologous groupCOG1061

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, 2 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 45.0 (very low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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
5umr-assembly1_A 0.33 0.74 2.3e+00 5umr-assembly1_A Crystal structure of N-terminal domain of human FACT complex subunit SSRP1
3nvx-assembly1_A 0.18 0.77 5.1e+00 3nvx-assembly1_A Molecular mechanism of guidance cue recognition
3cwy-assembly1_A-2 0.15 0.46 2.1e+00 3cwy-assembly1_A-2 Structure of CagD from H. pylori pathogenicity island crystallized in the presence of Cu(II) ions
3f0w-assembly1_A 0.15 0.50 2.2e+00 3f0w-assembly1_A Human NUMB-like protein, phosphotyrosine interaction domain
4wj7-assembly3_C 0.13 0.32 7.3e-01 4wj7-assembly3_C CCM2 PTB domain in complex with KRIT1 NPxY/F3
5njk-assembly3_C 0.13 0.55 3.4e+00 5njk-assembly3_C PTB domain of human Numb isoform-1
3nvx-assembly2_B 0.13 0.76 7.4e+00 3nvx-assembly2_B Molecular mechanism of guidance cue recognition
6vxk-assembly1_C 0.13 0.78 7.9e+00 6vxk-assembly1_C Cryo-EM Structure of the full-length A39R/PlexinC1 complex

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1329c dinG ATP-dependent helicase DinG 888 879 experimental:685 database:622
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 853 854 experimental:627 database:621
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 856 853 experimental:578 database:621
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 847 848 experimental:613 database:621
Rv1629 polA DNA polymerase I 787 768 experimental:430 database:580
Rv2090 5'-3' exonuclease 766 752 experimental:430 database:580
Rv2101 helZ helicase HelZ 711 689 database:615
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 688 688 database:620
Rv2529 hyp hypothetical protein 706 687 database:610
Rv1947 hyp hypothetical protein 636 636 ctx fusion:633
Rv1334 mec [CysO 630 630 database:613
Rv3036c TB22.2 hyp hypothetical protein 620 620 database:563
Rv3812 PE_PGRS62 PE-PGRS family protein PE_PGRS62 620 620 database:563
Rv2328 PE23 PE family protein PE23 620 620 database:563
Rv0832 PE_PGRS12 PE-PGRS family protein PE_PGRS12 620 620 database:563

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: 5umr-assembly1_A Crystal structure of N-terminal domain of human FACT complex su (prob 0.33, E=2e+00, TM=0.74)
  • (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_216477.1)
  • 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 COG1061
  • Curated reference: UniProt P95253 (TrEMBL, unreviewed; Predicted)
  • 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 45.0, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 36 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002076|Rv1961|
MFLPTNAQYQLLVVGVSPWDTPSPSGRISWGSAWPHQARRAQTCQRVRRHWMIDTTEAAYRLTYQPDGTSITVRENLVDILARELLGPIRGPQEVLPFSPRSQYLVGHLAPVKLTGAALIDDNAVQARANAEALAEGGGVPAYAADETTPTPTTTPKTAHPSRA