LBR

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003677 DNA binding	TAS PMID:8157662 Primary structure analysis and lamin B and DNA binding of hu...	KEEP AS NON CORE	Summary: The nucleoplasmic N-terminal domain of LBR binds double-stranded DNA in vitro (gel retardation, filter binding). Reason: DNA binding of the N-terminal domain is supported by in vitro assays (TAS here; also linker-DNA binding with high affinity in PMID:10828963) and contributes to chromatin tethering at the inner nuclear membrane, but it is a non-catalytic accessory property, not the core enzymatic function. Supporting Evidence: PMID:8157662 The LBR amino-terminal domain precipitates lamin B from nuclear extracts and retards the migration of double-stranded DNA subjected to agarose gel electrophoresis. PMID:10828963 Data show that the LBR amino-terminal domain (AT) binds linker DNA but does not interact with the nucleosome core.
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	KEEP AS NON CORE	Summary: Detected in a high-throughput mRNA interactome capture study. Reason: HDA RNA-binding from interactome capture. Plausible: LBR directly binds the Xist lncRNA (PMID:27492478), so RNA binding is a real but non-core property of the nucleoplasmic domain. Supporting Evidence: PMID:27492478 Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing
GO:0005515 protein binding	IPI PMID:26009488 Clnk plays a role in TNF-alpha-induced cell death in murine ...	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:28565870 C1QBP is upregulated in colon cancer and binds to apolipopro...	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:32694168 TMEM147 interacts with lamin B receptor, regulates its local...	REMOVE	Summary: TMEM147 physically interacts with LBR and regulates its INM localization and levels. Reason: Generic protein binding; the TMEM147 interaction is real but regulates LBR rather than being an LBR activity, and no informative MF term applies. Removal does not mean the interaction is false. Supporting Evidence: PMID:32694168 We show that TMEM147 physically interacts with LBR, and that the C-terminus of LBR is essential for their functional interaction.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: High-throughput or incidental interaction (large-scale interactome/proteomics or incidental pull-down); GO:0005515 protein binding conveys no functional information. Reason: Uninformative protein binding term from an interaction screen/incidental report; removal does not mean the interaction is false. LBR functions are already captured by Delta14-sterol reductase activity and its chromatin/lamina tethering terms.
GO:0005515 protein binding	IPI PMID:8663349 Interaction between an integral protein of the nuclear envel...	MODIFY	Summary: Two-hybrid, pull-down and co-IP binding of the LBR nucleoplasmic domain to HP1 chromodomain proteins. Reason: The interaction is specific and functionally meaningful: LBR carries a variant PxVxL motif recognized by the HP1 chromo shadow domain. A more informative term is chromo shadow domain binding. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:8663349 In a yeast two-hybrid screen, the nucleoplasmic domain of lamin B receptor (LBR), an integral protein of the inner nuclear membrane, associated with two human polypeptides homologous to Drosophila HP1 PMID:15882967 We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX.
GO:0005515 protein binding	IPI PMID:8663349 Interaction between an integral protein of the nuclear envel...	MODIFY	Summary: Two-hybrid, pull-down and co-IP binding of the LBR nucleoplasmic domain to HP1 chromodomain proteins. Reason: The interaction is specific and functionally meaningful: LBR carries a variant PxVxL motif recognized by the HP1 chromo shadow domain. A more informative term is chromo shadow domain binding. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:8663349 In a yeast two-hybrid screen, the nucleoplasmic domain of lamin B receptor (LBR), an integral protein of the inner nuclear membrane, associated with two human polypeptides homologous to Drosophila HP1 PMID:15882967 We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX.
GO:0005521 lamin binding	TAS PMID:8157662 Primary structure analysis and lamin B and DNA binding of hu...	KEEP AS NON CORE	Summary: The LBR N-terminal domain precipitates lamin B from nuclear extracts. Reason: Lamin B binding by the nucleoplasmic domain is the origin of the protein name and contributes to anchoring the lamina to the inner nuclear membrane; it is a structural, non-catalytic property. Supporting Evidence: PMID:8157662 The LBR amino-terminal domain precipitates lamin B from nuclear extracts and retards the migration of double-stranded DNA subjected to agarose gel electrophoresis.
GO:0005634 nucleus	IDA PMID:21327084 Mutations causing Greenberg dysplasia but not Pelger anomaly...	ACCEPT	Summary: LBR is in the nucleus (nuclear rim, inner nuclear membrane). Reason: Correct but general; the precise location is the inner nuclear membrane. Supporting Evidence: PMID:21327084 Unexpectedly we found in disease-relevant cell types not only nuclear but also cytoplasmatic LBR localization.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: LBR is in the nucleus (nuclear rim, inner nuclear membrane). Reason: Correct but general; the precise location is the inner nuclear membrane. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0005635 nuclear envelope	IEA GO_REF:0000120	ACCEPT	Summary: LBR is an integral protein of the nuclear envelope inner membrane. Reason: Correct localization (parent of nuclear inner membrane); Reactome places the LBR C14-reduction reaction and its mitotic/importin and MECP2 interactions at the nuclear envelope. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane
GO:0005635 nuclear envelope	TAS Reactome:R-HSA-194674	ACCEPT	Summary: LBR is an integral protein of the nuclear envelope inner membrane. Reason: Correct localization (parent of nuclear inner membrane); Reactome places the LBR C14-reduction reaction and its mitotic/importin and MECP2 interactions at the nuclear envelope. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane Reactome:R-HSA-194674 catalyzed by LBR in the nuclear envelope
GO:0005635 nuclear envelope	TAS Reactome:R-HSA-9018594	ACCEPT	Summary: LBR is an integral protein of the nuclear envelope inner membrane. Reason: Correct localization (parent of nuclear inner membrane); Reactome places the LBR C14-reduction reaction and its mitotic/importin and MECP2 interactions at the nuclear envelope. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane
GO:0005635 nuclear envelope	TAS Reactome:R-HSA-9624798	ACCEPT	Summary: LBR is an integral protein of the nuclear envelope inner membrane. Reason: Correct localization (parent of nuclear inner membrane); Reactome places the LBR C14-reduction reaction and its mitotic/importin and MECP2 interactions at the nuclear envelope. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane
GO:0005635 nuclear envelope	TAS Reactome:R-HSA-9624800	ACCEPT	Summary: LBR is an integral protein of the nuclear envelope inner membrane. Reason: Correct localization (parent of nuclear inner membrane); Reactome places the LBR C14-reduction reaction and its mitotic/importin and MECP2 interactions at the nuclear envelope. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane
GO:0005637 nuclear inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: LBR is a polytopic integral membrane protein of the inner nuclear membrane. Reason: Principal, well-established location of LBR, where it carries both the sterol reductase domain and the chromatin/lamina-tethering nucleoplasmic domain. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0005637 nuclear inner membrane	IDA PMID:32694168 TMEM147 interacts with lamin B receptor, regulates its local...	ACCEPT	Summary: LBR is a polytopic integral membrane protein of the inner nuclear membrane. Reason: Principal, well-established location of LBR, where it carries both the sterol reductase domain and the chromatin/lamina-tethering nucleoplasmic domain. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0005637 nuclear inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: LBR is a polytopic integral membrane protein of the inner nuclear membrane. Reason: Principal, well-established location of LBR, where it carries both the sterol reductase domain and the chromatin/lamina-tethering nucleoplasmic domain. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0005637 nuclear inner membrane	TAS PMID:8157662 Primary structure analysis and lamin B and DNA binding of hu...	ACCEPT	Summary: LBR is a polytopic integral membrane protein of the inner nuclear membrane. Reason: Principal, well-established location of LBR, where it carries both the sterol reductase domain and the chromatin/lamina-tethering nucleoplasmic domain. Supporting Evidence: PMID:8157662 We have determined the primary structure of human LBR, an integral protein of the nuclear envelope inner membrane file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0005652 nuclear lamina	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Associates with the nuclear lamina via its nucleoplasmic domain. Reason: LBR is an inner nuclear membrane protein that binds lamin B; is_active_in nuclear lamina is defensible as association rather than residence. The INM term is the precise location. Supporting Evidence: PMID:8157662 The LBR amino-terminal domain precipitates lamin B from nuclear extracts and retards the migration of double-stranded DNA subjected to agarose gel electrophoresis. PMID:27492478 Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing
GO:0005737 cytoplasm	IDA PMID:21327084 Mutations causing Greenberg dysplasia but not Pelger anomaly...	KEEP AS NON CORE	Summary: Cytoplasmic (ER-colocalizing) LBR staining in disease-relevant cell types. Reason: The cytoplasmic pool co-localizes with ER markers; endoplasmic reticulum membrane is the more precise term and is also annotated. Cytoplasm is not wrong but is uninformative. Supporting Evidence: PMID:21327084 The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cytoplasmic (ER-colocalizing) LBR staining in disease-relevant cell types. Reason: The cytoplasmic pool co-localizes with ER markers; endoplasmic reticulum membrane is the more precise term and is also annotated. Cytoplasm is not wrong but is uninformative. Supporting Evidence: PMID:21327084 The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:21327084 Mutations causing Greenberg dysplasia but not Pelger anomaly...	ACCEPT	Summary: A pool of LBR is in the ER membrane, continuous with the nuclear envelope. Reason: Experimentally observed (co-localization with ER markers) and consistent with sterol synthesis sites; LBR is synthesized in the ER and diffuses to the INM. Supporting Evidence: PMID:21327084 The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: A pool of LBR is in the ER membrane, continuous with the nuclear envelope. Reason: Experimentally observed (co-localization with ER markers) and consistent with sterol synthesis sites; LBR is synthesized in the ER and diffuses to the INM. Supporting Evidence: PMID:21327084 The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis.
GO:0006695 cholesterol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: LBR catalyzes the C14 reduction step in post-lanosterol cholesterol biosynthesis. Reason: Core process. LBR knockout cells lose cholesterol synthesis and patient (Greenberg) cells accumulate the C14-unsaturated intermediate, rescued by wild-type LBR. Supporting Evidence: PMID:27336722 We demonstrate that human LBR is essential for cholesterol synthesis. PMID:12618959 Functional complementation of the HEM cells by transfection with control LBR cDNA confirmed that LBR encoded the defective sterol delta(14)-reductase.
GO:0006695 cholesterol biosynthetic process	IDA PMID:16784888 Sterol dependent regulation of human TM7SF2 gene expression:...	ACCEPT	Summary: LBR catalyzes the C14 reduction step in post-lanosterol cholesterol biosynthesis. Reason: Core process. LBR knockout cells lose cholesterol synthesis and patient (Greenberg) cells accumulate the C14-unsaturated intermediate, rescued by wild-type LBR. Supporting Evidence: PMID:16784888 Both human C14SR and LBR expressed in COS-1 cells exhibit 3beta-hydroxysterol Delta(14)-reductase activity in vitro.
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: LBR catalyzes the C14 reduction step in post-lanosterol cholesterol biosynthesis. Reason: Core process. LBR knockout cells lose cholesterol synthesis and patient (Greenberg) cells accumulate the C14-unsaturated intermediate, rescued by wild-type LBR. Supporting Evidence: file:human/LBR/LBR-uniprot.txt Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis
GO:0006695 cholesterol biosynthetic process	IMP PMID:27336722 The Lamin B receptor is essential for cholesterol synthesis ...	ACCEPT	Summary: LBR catalyzes the C14 reduction step in post-lanosterol cholesterol biosynthesis. Reason: Core process. LBR knockout cells lose cholesterol synthesis and patient (Greenberg) cells accumulate the C14-unsaturated intermediate, rescued by wild-type LBR. Supporting Evidence: PMID:27336722 Notably, we observed a near-complete loss of cholesterol synthesis in LBR KO cells PMID:27336722 We demonstrate that human LBR is essential for cholesterol synthesis.
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-6807047	ACCEPT	Summary: LBR catalyzes the C14 reduction step in post-lanosterol cholesterol biosynthesis. Reason: Core process. LBR knockout cells lose cholesterol synthesis and patient (Greenberg) cells accumulate the C14-unsaturated intermediate, rescued by wild-type LBR. Supporting Evidence: Reactome:R-HSA-194674 catalyzed by LBR in the nuclear envelope
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: LBR is a multi-pass integral membrane protein. Reason: Correct but very general; INM and ER membrane are the specific locations. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0016020 membrane	IDA PMID:15698635 Increased susceptibility of glutathione peroxidase-1 transge...	ACCEPT	Summary: LBR is a multi-pass integral membrane protein. Reason: Correct but very general; INM and ER membrane are the specific locations. The cited paper (a GPX1 transgenic-mouse seizure study, abstract only in the cache) does not mention LBR in its abstract, so the reference may be miscited; the location itself is not in doubt and is supported by the transmembrane topology. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: LBR is a multi-pass integral membrane protein. Reason: Correct but very general; INM and ER membrane are the specific locations. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0016126 sterol biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Sterol biosynthetic process (InterPro2GO). Reason: Correct general parent of the core process cholesterol biosynthetic process. Supporting Evidence: file:human/LBR/LBR-uniprot.txt Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis
GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors	IEA GO_REF:0000117	MODIFY	Summary: Generic oxidoreductase class term from automated pipelines. Reason: Correct but too general; the specific, experimentally established activity is NADPH-dependent Delta14-sterol reductase activity. Proposed replacements: Delta14-sterol reductase activity Supporting Evidence: PMID:9630650 Our results strongly suggest that hLBR is a sterol C14 reductase. file:human/LBR/LBR-uniprot.txt Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis
GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	IEA GO_REF:0000002	MODIFY	Summary: Generic oxidoreductase class term from automated pipelines. Reason: Correct but too general; the specific, experimentally established activity is NADPH-dependent Delta14-sterol reductase activity. Proposed replacements: Delta14-sterol reductase activity Supporting Evidence: PMID:9630650 Our results strongly suggest that hLBR is a sterol C14 reductase. file:human/LBR/LBR-uniprot.txt Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis
GO:0030223 neutrophil differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neutrophil differentiation (transferred from mouse Lbr). Reason: LBR dosage controls neutrophil nuclear segmentation (Pelger-Huet anomaly in humans; ichthyosis mice), and mouse studies link LBR-dependent cholesterol synthesis to myeloid maturation. A real but downstream, cell-type-specific role rather than core function. Supporting Evidence: PMID:12118250 We found that expression of the lamin B receptor affects neutrophil nuclear shape and chromatin distribution in a dose-dependent manner.
GO:0030223 neutrophil differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Neutrophil differentiation (transferred from mouse Lbr). Reason: LBR dosage controls neutrophil nuclear segmentation (Pelger-Huet anomaly in humans; ichthyosis mice), and mouse studies link LBR-dependent cholesterol synthesis to myeloid maturation. A real but downstream, cell-type-specific role rather than core function. Supporting Evidence: PMID:12118250 We found that expression of the lamin B receptor affects neutrophil nuclear shape and chromatin distribution in a dose-dependent manner.
GO:0031965 nuclear membrane	IDA GO_REF:0000052	ACCEPT	Summary: Nuclear membrane localization (immunofluorescence / ortholog transfer). Reason: Correct; LBR is in the inner nuclear membrane. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0031965 nuclear membrane	IEA GO_REF:0000107	ACCEPT	Summary: Nuclear membrane localization (immunofluorescence / ortholog transfer). Reason: Correct; LBR is in the inner nuclear membrane. Supporting Evidence: file:human/LBR/LBR-uniprot.txt SUBCELLULAR LOCATION: Nucleus inner membrane
GO:0036197 zymosterol biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Zymosterol biosynthetic process (ortholog transfer). Reason: The C14 reduction catalyzed by LBR lies upstream of zymosterol formation in the Bloch branch, so the term is consistent, but cholesterol biosynthetic process is the core process. Supporting Evidence: Reactome:R-HSA-194674 catalyzed by LBR in the nuclear envelope
GO:0050613 Delta14-sterol reductase activity	IBA GO_REF:0000033	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:9630650 Our results strongly suggest that hLBR is a sterol C14 reductase. PMID:12618959 Functional complementation of the HEM cells by transfection with control LBR cDNA confirmed that LBR encoded the defective sterol delta(14)-reductase.
GO:0050613 Delta14-sterol reductase activity	IDA PMID:16784888 Sterol dependent regulation of human TM7SF2 gene expression:...	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:16784888 Both human C14SR and LBR expressed in COS-1 cells exhibit 3beta-hydroxysterol Delta(14)-reductase activity in vitro.
GO:0050613 Delta14-sterol reductase activity	IDA PMID:9630650 Human lamin B receptor exhibits sterol C14-reductase activit...	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:9630650 Our results strongly suggest that hLBR is a sterol C14 reductase. PMID:9630650 the sterol C14 reduction step and ergosterol prototrophy were restored in LBR-producing erg24 transformants which lack endogenous sterol C14 reductase.
GO:0050613 Delta14-sterol reductase activity	IEA GO_REF:0000120	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: file:human/LBR/LBR-uniprot.txt Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis
GO:0050613 Delta14-sterol reductase activity	IMP PMID:12618959 Autosomal recessive HEM/Greenberg skeletal dysplasia is caus...	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:12618959 Functional complementation of the HEM cells by transfection with control LBR cDNA confirmed that LBR encoded the defective sterol delta(14)-reductase.
GO:0050613 Delta14-sterol reductase activity	IMP PMID:21327084 Mutations causing Greenberg dysplasia but not Pelger anomaly...	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:21327084 In contrast to wildtype LBR, both mutations failed to rescue C14 sterol reductase deficient yeast, indicating an enzymatic defect.
GO:0050613 Delta14-sterol reductase activity	IMP PMID:27336722 The Lamin B receptor is essential for cholesterol synthesis ...	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: PMID:27336722 We demonstrate that human LBR is essential for cholesterol synthesis.
GO:0050613 Delta14-sterol reductase activity	TAS Reactome:R-HSA-194674	ACCEPT	Summary: LBR has 3-beta-hydroxysterol Delta14-reductase (sterol C14 reductase) activity. Reason: Core enzymatic function, shown by yeast erg24 complementation, in vitro assay of expressed protein, complementation of Greenberg patient cells, and loss of activity in disease alleles. Supporting Evidence: Reactome:R-HSA-194674 catalyzed by LBR in the nuclear envelope
GO:0060816 random inactivation of X chromosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Random X inactivation (ortholog transfer from mouse). Reason: In mouse cells Xist directly binds LBR, and this is required to recruit the inactive X to the nuclear lamina for chromosome-wide silencing. A real but specialized role of the nucleoplasmic domain. Supporting Evidence: PMID:27492478 Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing
GO:0070087 chromo shadow domain binding	IPI PMID:15882967 The mammalian heterochromatin protein 1 binds diverse nuclea...	ACCEPT	Summary: LBR binds the HP1 chromo shadow domain via a variant PxVxL motif. Reason: Specific direct binding activity underlying LBR tethering of heterochromatin to the inner nuclear membrane. Supporting Evidence: PMID:15882967 We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX. PMID:8663349 In a yeast two-hybrid screen, the nucleoplasmic domain of lamin B receptor (LBR), an integral protein of the inner nuclear membrane, associated with two human polypeptides homologous to Drosophila HP1
GO:0070402 NADPH binding	IMP PMID:27336722 The Lamin B receptor is essential for cholesterol synthesis ...	KEEP AS NON CORE	Summary: NADPH is the essential cofactor of the LBR sterol reductase domain; disease mutants lose NADPH affinity. Reason: Direct binding measured on purified protein (tryptophan fluorescence), with disease alleles reducing affinity, so the annotation is well supported. NADPH is the reductase's own cofactor and its binding is part of the Delta14-sterol reductase activity captured as the core function, so it is kept as non-core, as cofactor binding is treated for COQ6 (FAD), COQ7 (iron) and MSMO1 (iron). That disease alleles lower NADPH affinity explains how they impair the reductase core function. Supporting Evidence: PMID:27336722 Disease-associated LBR point mutants LBR N547D and LBR R583Q show a decreased affinity for NADPH compared to wild-type LBR.
GO:0140463 chromatin-protein adaptor activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Chromatin-protein adaptor activity (ortholog transfer). Reason: LBR tethers heterochromatin (via its Tudor domain, HP1 and DNA binding) to the inner nuclear membrane. GO:0140463 is defined as "An adaptor activity that brings together a protein and a region of the chromatin, such as a nucleosome, to establish or maintain the chromatin localization of the protein, or the complex to which it belongs". Unlike its symmetric parent GO:0030674, the term is directional: its outcome is a protein positioned on chromatin. LBR's outcome is the reverse, chromatin positioned at the nuclear envelope by a membrane-anchored protein. The specific binding activities (H4K20me2 reading, GO:0140005; chromo shadow domain binding, GO:0070087) describe what LBR does more accurately. The ortholog-transferred term is not wrong in spirit, so it is marked over-annotated rather than removed. Supporting Evidence: PMID:12118250 it targets heterochromatin and lamins to the nuclear membrane. PMID:15882967 We also define a new class of variant PxVxL CSD-binding motifs in Sp100A, LBR, and ATRX.
GO:0140005 histone H4K20me2 reader activity	IDA PMID:23100253 Lamin B receptor recognizes specific modifications of histon...	NEW	Summary: Proposed new annotation. The nucleoplasmic Tudor domain of human LBR preferentially binds histone H4 dimethylated at lysine 20 in peptide-array and recombinant-histone binding assays, and LBR co-localizes with H4K20me2 beneath the inner nuclear membrane by ChIP. Reason: Absent from GOA. The binding is a property of LBR itself (its Tudor domain), shown with purified LBR fragments rather than inferred from LBR being required for heterochromatin tethering, so it describes work LBR does. It is the specific molecular basis of LBR's chromatin-tethering role, alongside the HP1 chromo shadow domain binding already captured by MODIFY to GO:0070087. Supporting Evidence: PMID:23100253 the tudor domain of LBR primarily recognizes histone H4 lysine 20 dimethylation (H4K20me2) to recruit epigenetically marked chromatin to the NE. PMID:23100253 Taken together, we concluded that LBR binds to at least H4K20me2.

Gene Description

Existing Annotations Review

Core Functions

NADPH-dependent 3-beta-hydroxysterol Delta14-reductase catalysing reduction of the C14 double bond of lanosterol-derived sterol intermediates in post-squalene cholesterol biosynthesis, acting in the inner nuclear membrane/ER.

Structural tethering of peripheral heterochromatin to the inner nuclear membrane through binding of the nucleoplasmic domain to the HP1 chromo shadow domain (and to DNA and lamin B).

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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