bisC Resolved · high auto-curated

H37Rv Rv1442 · MTBC0 mtbc0_001543 · 766 aa · 1629159–1631459 (+) · RefSeq NP_215958.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)biotin sulfoxide reductase BisC
MTBC0 PGAP re-annotationmolybdopterin guanine dinucleotide-containing S/N-oxide reductase
Revised (this work)Molybdopterin guanine dinucleotide-containing S/N-oxide reductase. Pfam: Molybdopterin_N (PF18364.7), Molybdopterin (PF00384.28), Molydop_binding (PF01568.28).

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

Curated reference (UniProt)

UniProt O06817 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable biotin sulfoxide reductase BisC

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namebisC
eggNOG descriptionBelongs to the prokaryotic molybdopterin-containing oxidoreductase family
Orthologous groupCOG0243
EC number EC 1.8.5.3, EC 1.97.1.9
KEGG orthology K07306, K07309, K07310, K08351
KEGG pathways map00450, map00780, map00920, map01100

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 1.033 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 12 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
Molybdopterin_NPF18364.7 3.0e-126–46 Molybdopterin oxidoreductase N-terminal domain
MolybdopterinPF00384.28 8.6e-4350–510 Molybdopterin oxidoreductase
Molydop_bindingPF01568.28 3.4e-22623–739 Molydopterin dinucleotide binding domain

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

Closest characterised functional partner: PE_PGRS26 (PE-PGRS family protein PE_PGRS26), medium confidence from genomic context alone (score 593 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3279c birA bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase 904 902 database:900
Rv1589 bioB biotin synthetase 900 900 database:900
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 816 797 experimental:774
Rv0685 tuf elongation factor Tu 807 791 experimental:783
Rv1441c PE_PGRS26 PE-PGRS family protein PE_PGRS26 593 593 ctx neighborhood:593
Rv3859c gltB glutamate synthase large subunit 768 573 experimental:420 textmining:481
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 558 512 experimental:484
Rv1162 narH nitrate reductase subunit beta 637 458 experimental:431
Rv3273 transmembrane carbonic anhydrase 406 377
Rv2899c fdhD formate dehydrogenase accessory protein FdhD 407 343
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 404 340
Rv0984 moaB2 pterin-4-alpha-carbinolamine dehydratase 561 223 textmining:459
Rv0233 nrdB ribonucleoside-diphosphate reductase subunit beta NrdB 719 214 textmining:658
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 412 178
Rv1857 modA molybdate ABC transporter substrate-binding lipoprotein ModA 644 111 textmining:616

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: biotin sulfoxide reductase BisC
  • MTBC0 PGAP product: molybdopterin guanine dinucleotide-containing S/N-oxide reductase
  • Pfam (hmmscan --cut_ga): Molybdopterin_N PF18364.7 (E=3e-12), Molybdopterin PF00384.28 (E=9e-43), Molydop_binding PF01568.28 (E=3e-22)
  • (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_215958.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Molybdopterin_N (PF18364.7), Molybdopterin (PF00384.28), Molydop_binding (PF01568.28)
  • 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 COG0243
  • Curated reference: UniProt O06817 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 16 functional partner(s); context anchor PE_PGRS26
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001543|Rv1442|bisC
MQVYTSATHWGVFTARVHGGDIAAVAALASDTNPAPQLQNLPGAVRHRSRIANPAVRRGWLQHGPGPSSARGAEEFVEVSWDELIELLASELRRTVDRYGNEAIYGSSYGWASAGRFHHAQSQVHRFLNMLGGYTASRHSYSAGASEVIFPHIVGAALFEALAETTTWDVIVDHTALLVAFGGLPVKNTAVMPGGTTAHPDRDYVGRYRARGGRLVSVSPLRDDIAAIAGPLDDRCRWLAPVPGTDVAIMLGLAYVLATESLADRAFLGRYCTGYERFERYLLGLDDGIPKTPEWAAALSGLAAGDLRDLARRMAEHRTLITTSLSLQRIEHGEQTVWMAATLAAMLGQIGLPGGGFGHGYSSNGVGNPPLACGLPALPQGNNPVSTFIPVAAISELLQRPGQRLAYNGRLLELPDIKCVYWAGGNPFHHHQNLPRLRRALSRVDTIVVHEQYWTAMAKHADIVVPTTTSFERDDFAASKTNPTLIAMPAMVPPYANARDDYHTFSALAHRLGFGKQFTEGRSAREWLEHMYDKWSAELDFPVPSFAEFWRTGRLELPTRTGLTWLADFRADPAAHPLGTPSGRIEIFSDTVDAFALPDCAGHPTWYEPSEWLGGPRAARYPLHLIANQPRTRLHSQLDHGGASMASKIRGREPIRIHPDDAAARELTDGDIVRVFNDRGACLAGVVIDDGLRPKVVQLSTGAWFDPADPRDPDSMCVHGNPNALSNDSGTSSLAHGSTGQHVLVQIERFTGELPPVRAHEPPRLA