LBR (lamin B receptor, Q14739) — review notes

Literature work done manually from cached publications/ (PubMed MCP used to
locate additional PMIDs, which were then fetched with just fetch-pmid).

Enzymatic function (core)

• Sterol C14 reductase: human LBR complements yeast erg24 (C14 reductase)
  mutants but not erg4 PMID:9630650.
• Expressed LBR has Delta14-reductase activity in vitro PMID:16784888; the same paper argued TM7SF2 (C14SR)
  is the sterol-regulated, ER enzyme and that LBR's role "remains unclear".
• Greenberg/HEM dysplasia: patient fibroblasts accumulate
  cholesta-8,14-dien-3beta-ol and are complemented by wild-type LBR
  PMID:12618959.
• Greenberg missense alleles at conserved sterol-reductase residues fail yeast
  complementation PMID:21327084.
• LBR is essential for cholesterol synthesis in human cells despite TM7SF2
  PMID:27336722; disease point mutants lose NADPH affinity PMID:27336722.

Localization

• Inner nuclear membrane integral protein PMID:8157662; an ER pool
  PMID:21327084.

Structural / chromatin functions (non-core for GO purposes but real)

• N-terminal domain binds lamin B and DNA PMID:8157662, linker DNA with high
  affinity PMID:10828963, HP1 proteins PMID:8663349 via a variant PxVxL
  chromo-shadow-domain-binding motif PMID:15882967.
• Dosage-dependent control of neutrophil nuclear shape; heterozygous loss =
  Pelger-Huet anomaly PMID:12118250.
• Xist binds LBR to recruit the inactive X to the lamina (mouse) PMID:27492478.

Curation decisions

• GO:0005515 protein binding: HP1 paper (PMID:8663349) MODIFY to chromo shadow
  domain binding; all others REMOVE as uninformative.
• GO:0140463 chromatin-protein adaptor activity (IEA, ortholog): marked
  over-annotated — geometry is the reverse of the definition.
• Oxidoreductase class IEA terms: MODIFY to GO:0050613.

Pathway placement

• Post-squalene cholesterol synthesis; C14 reduction of
  4,4-dimethylcholesta-8,14,24-trienol (FF-MAS -> T-MAS) in the Bloch branch
  (Reactome R-HSA-194674). Module cholesterol_synthesis_post_lanosterol is
  owned by another group (W2-CHOL-A).

Deep research

just deep-research-falcon human LBR was attempted on 2026-10-09 and first failed
("All providers failed"), so the literature review above was done manually. A later falcon run
succeeded and is committed as LBR-deep-research-falcon.md. It adds the Tudor-domain H4K20me2
recognition (Hirano et al. 2012, PMID:23100253), now captured as a NEW GO:0140005 annotation.