hycP Family assigned · medium

H37Rv Rv0085 · MTBC0 mtbc0_000095 · 220 aa · 93452–94114 (+) · RefSeq NP_214599.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrogenase HycP
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Polytopic integral membrane protein with 7 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hydrogenase HycP'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined.

Curated reference (UniProt)

UniProt P9WM75 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv0085

UniProt still lists this protein as Uncharacterized protein Rv0085; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namehycP
eggNOG descriptionHydrogenase 4 membrane
Orthologous groupCOG4237
KEGG orthology K12140
Gene Ontology (2) GO:0008150, GO:0040007

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 0.686 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 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).

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

Closest characterised functional partner: hycQ (hydrogenase HycQ), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0086 hycQ hydrogenase HycQ 999 996 ctx neighborhood:882 cooccurence:774 coexpression:860 textmining:826
Rv0087 hycE formate hydrogenase HycE 999 996 ctx neighborhood:892 cooccurence:774 coexpression:860 textmining:870
Rv0083 oxidoreductase 996 996 ctx neighborhood:874 cooccurence:774 coexpression:860
Rv0082 oxidoreductase 994 994 ctx neighborhood:874 cooccurence:736 coexpression:824
Rv0084 hycD formate hydrogenlyase HycD 992 992 ctx neighborhood:874 cooccurence:774 coexpression:731
Rv0081 HTH-type transcriptional regulator 944 921 ctx neighborhood:874
Rv0088 polyketide cyclase/dehydrase 666 666 ctx neighborhood:658
Rv0080 hyp hypothetical protein 545 545 ctx neighborhood:542
Rv0079 hyp hypothetical protein 540 540 ctx neighborhood:538
Rv0089 methyltransferase 435 435 ctx neighborhood:427
Rv1735c membrane protein 553 54 textmining:547
Rv1519 hyp hypothetical protein 625 47 textmining:623
Rv3126c hyp hypothetical protein 549 44 textmining:548
Rv2526 vapB17 antitoxin VapB17 439 41 textmining:439
Rv0748 vapB31 antitoxin VapB31 438 41 textmining:438

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

  • DeepTMHMM: 7 transmembrane helices (type TM)
  • Integral membrane topology (localisation feature, not a function)
  • DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.

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_214599.1)
  • 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 COG4237
  • Curated reference: UniProt P9WM75 (SwissProt, reviewed; 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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 15 functional partner(s); context anchor hycQ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000095|Rv0085|hycP
MSNANFSILVDFAAGGLVLASVLIVWRRDLRAIVRLLAWQGAALAAIPLLRGIRDNDRALIAVGIAVLALRALVLPWLLARAVGAEAAAQREATPLVNTASSLLITAGLTLTAFAITQPVVNLEPGVTINAVPAAFAVVLIALFVMTTRLHAVSQAAGFLMLDNGIAATAFLLTAGVPLIVELGASLDVLFAVIVIGVLTGRLRRIFGDADLDKLRELRD