LBR_HUMAN
ID LBR_HUMAN Reviewed; 615 AA.
AC Q14739; B2R5P3; Q14740; Q53GU7; Q59FE6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Delta(14)-sterol reductase LBR;
DE Short=Delta-14-SR;
DE EC=1.3.1.70 {ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:9630650};
DE AltName: Full=3-beta-hydroxysterol Delta (14)-reductase {ECO:0000303|PubMed:16784888};
DE AltName: Full=C-14 sterol reductase;
DE Short=C14SR;
DE AltName: Full=Integral nuclear envelope inner membrane protein {ECO:0000303|PubMed:10828963};
DE AltName: Full=LMN2R;
DE AltName: Full=Lamin-B receptor {ECO:0000303|PubMed:8157662, ECO:0000303|PubMed:8157663};
DE AltName: Full=Sterol C14-reductase;
GN Name=LBR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DNA AND LAMIN B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=8157662; DOI=10.1016/s0021-9258(19)78126-5;
RA Ye Q., Worman H.J.;
RT "Primary structure analysis and lamin B and DNA binding of human LBR, an
RT integral protein of the nuclear envelope inner membrane.";
RL J. Biol. Chem. 269:11306-11311(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-154.
RX PubMed=8157663; DOI=10.1016/s0021-9258(19)78127-7;
RA Schuler E., Lin F., Worman H.J.;
RT "Characterization of the human gene encoding LBR, an integral protein of
RT the nuclear envelope inner membrane.";
RL J. Biol. Chem. 269:11312-11317(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-154.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-154.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-154.
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-154.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH CBX5.
RX PubMed=9169472; DOI=10.1074/jbc.272.23.14983;
RA Ye Q., Callebaut I., Pezhman A., Courvalin J.-C., Worman H.J.;
RT "Domain-specific interactions of human HP1-type chromodomain proteins and
RT inner nuclear membrane protein LBR.";
RL J. Biol. Chem. 272:14983-14989(1997).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9630650; DOI=10.1016/s0005-2760(98)00041-1;
RA Silve S., Dupuy P.H., Ferrara P., Loison G.;
RT "Human lamin B receptor exhibits sterol C14-reductase activity in
RT Saccharomyces cerevisiae.";
RL Biochim. Biophys. Acta 1392:233-244(1998).
RN [10]
RP PHOSPHORYLATION BY SRPK1.
RX PubMed=10049757; DOI=10.1006/bbrc.1999.0249;
RA Papoutsopoulou S., Nikolakaki E., Giannakouros T.;
RT "SRPK1 and LBR protein kinases show identical substrate specificities.";
RL Biochem. Biophys. Res. Commun. 255:602-607(1999).
RN [11]
RP FUNCTION.
RX PubMed=10828963; DOI=10.1021/bi992908b;
RA Duband-Goulet I., Courvalin J.-C.;
RT "Inner nuclear membrane protein LBR preferentially interacts with DNA
RT secondary structures and nucleosomal linker.";
RL Biochemistry 39:6483-6488(2000).
RN [12]
RP DISEASE.
RX PubMed=12118250; DOI=10.1038/ng925;
RA Hoffmann K., Dreger C.K., Olins A.L., Olins D.E., Shultz L.D., Lucke B.,
RA Karl H., Kaps R., Mueller D., Vaya A., Aznar J., Ware R.E., Sotelo Cruz N.,
RA Lindner T.H., Herrmann H., Reis A., Sperling K.;
RT "Mutations in the gene encoding the lamin B receptor produce an altered
RT nuclear morphology in granulocytes (Pelger-Huet anomaly).";
RL Nat. Genet. 31:410-414(2002).
RN [13]
RP INVOLVEMENT IN GRBGD, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12618959; DOI=10.1086/373938;
RA Waterham H.R., Koster J., Mooyer P., van Noort G., Kelley R.I.,
RA Wilcox W.R., Wanders R.J., Hennekam R.C.M., Oosterwijk J.C.;
RT "Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-
RT hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B
RT receptor gene.";
RL Am. J. Hum. Genet. 72:1013-1017(2003).
RN [14]
RP INTERACTION WITH CBX5.
RX PubMed=15882967; DOI=10.1016/j.bbrc.2005.04.016;
RA Lechner M.S., Schultz D.C., Negorev D., Maul G.G., Rauscher F.J. III;
RT "The mammalian heterochromatin protein 1 binds diverse nuclear proteins
RT through a common motif that targets the chromoshadow domain.";
RL Biochem. Biophys. Res. Commun. 331:929-937(2005).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=16784888; DOI=10.1016/j.bbalip.2006.05.004;
RA Bennati A.M., Castelli M., Della Fazia M.A., Beccari T., Caruso D.,
RA Servillo G., Roberti R.;
RT "Sterol dependent regulation of human TM7SF2 gene expression: role of the
RT encoded 3beta-hydroxysterol Delta14-reductase in human cholesterol
RT biosynthesis.";
RL Biochim. Biophys. Acta 1761:677-685(2006).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55; LYS-594 AND LYS-601, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97 AND THR-118, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION AT SER-71 AND SER-86 BY CDK1.
RX PubMed=21795390; DOI=10.1091/mbc.e11-03-0199;
RA Tseng L.C., Chen R.H.;
RT "Temporal control of nuclear envelope assembly by phosphorylation of lamin
RT B receptor.";
RL Mol. Biol. Cell 22:3306-3317(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58; SER-59; SER-128 AND
RP THR-200, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP INTERACTION WITH CLNK.
RX PubMed=26009488; DOI=10.1016/j.bbrc.2015.05.046;
RA Xu M., Cai C., Sun X., Chen W., Li Q., Zhou H.;
RT "Clnk plays a role in TNF-alpha-induced cell death in murine fibrosarcoma
RT cell line L929.";
RL Biochem. Biophys. Res. Commun. 463:275-279(2015).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [27]
RP STRUCTURE BY NMR OF 1-55.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the Tudor domain of human lamin-B receptor.";
RL Submitted (SEP-2006) to the PDB data bank.
RN [28]
RP STRUCTURE BY NMR OF 1-55.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the Tudor domain of human lamin-B receptor.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [29]
RP VARIANTS PHA LEU-119 AND ARG-569.
RX PubMed=14617022; DOI=10.1046/j.1365-2141.2003.04621.x;
RA Best S., Salvati F., Kallo J., Garner C., Height S., Thein S.L., Rees D.C.;
RT "Lamin B-receptor mutations in Pelger-Huet anomaly.";
RL Br. J. Haematol. 123:542-544(2003).
RN [30]
RP VARIANT REYNS CYS-372.
RX PubMed=20522425; DOI=10.1136/jmg.2009.071696;
RA Gaudy-Marqueste C., Roll P., Esteves-Vieira V., Weiller P.J., Grob J.J.,
RA Cau P., Levy N., De Sandre-Giovannoli A.;
RT "LBR mutation and nuclear envelope defects in a patient affected with
RT Reynolds syndrome.";
RL J. Med. Genet. 47:361-370(2010).
RN [31]
RP VARIANTS GRBGD ASP-547 AND GLN-583, CHARACTERIZATION OF VARIANTS GRBGD
RP ASP-547 AND GLN-583, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=21327084; DOI=10.4161/nucl.1.4.12435;
RA Clayton P., Fischer B., Mann A., Mansour S., Rossier E., Veen M., Lang C.,
RA Baasanjav S., Kieslich M., Brossuleit K., Gravemann S., Schnipper N.,
RA Karbasyian M., Demuth I., Zwerger M., Vaya A., Utermann G., Mundlos S.,
RA Stricker S., Sperling K., Hoffmann K.;
RT "Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple
RT enzymatic from structural functions of a nuclear membrane protein.";
RL Nucleus 1:354-366(2010).
RN [32]
RP INVOLVEMENT IN PHASK, AND VARIANT PHASK HIS-586.
RX PubMed=23824842; DOI=10.1002/ajmg.a.36019;
RA Borovik L., Modaff P., Waterham H.R., Krentz A.D., Pauli R.M.;
RT "Pelger-huet anomaly and a mild skeletal phenotype secondary to mutations
RT in LBR.";
RL Am. J. Med. Genet. A 161A:2066-2073(2013).
RN [33]
RP INVOLVEMENT IN PHASK, AND VARIANTS PHASK SER-547 AND 76-ARG--TYR-615 DEL.
RX PubMed=25348816; DOI=10.1002/ajmg.a.36808;
RA Sobreira N., Modaff P., Steel G., You J., Nanda S., Hoover-Fong J.,
RA Valle D., Pauli R.M.;
RT "An anadysplasia-like, spontaneously remitting spondylometaphyseal
RT dysplasia secondary to lamin B receptor (LBR) gene mutations: further
RT definition of the phenotypic heterogeneity of LBR-bone dysplasias.";
RL Am. J. Med. Genet. A 167A:159-163(2015).
RN [34]
RP CHARACTERIZATION OF VARIANTS GRBGD ASP-547 AND GLN-583, AND FUNCTION.
RX PubMed=27336722; DOI=10.7554/elife.16011;
RA Tsai P.L., Zhao C., Turner E., Schlieker C.;
RT "The Lamin B receptor is essential for cholesterol synthesis and perturbed
RT by disease-causing mutations.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Catalyzes the reduction of the C14-unsaturated bond of
CC lanosterol, as part of the metabolic pathway leading to cholesterol
CC biosynthesis (PubMed:9630650, PubMed:12618959, PubMed:16784888,
CC PubMed:21327084, PubMed:27336722). Plays a critical role in myeloid
CC cell cholesterol biosynthesis which is essential to both myeloid cell
CC growth and functional maturation (By similarity). Mediates the
CC activation of NADPH oxidases, perhaps by maintaining critical levels of
CC cholesterol required for membrane lipid raft formation during
CC neutrophil differentiation (By similarity). Anchors the lamina and the
CC heterochromatin to the inner nuclear membrane (PubMed:10828963).
CC {ECO:0000250|UniProtKB:Q3U9G9, ECO:0000269|PubMed:10828963,
CC ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:16784888,
CC ECO:0000269|PubMed:21327084, ECO:0000269|PubMed:27336722,
CC ECO:0000269|PubMed:9630650}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-cholest-8,14-dien-3beta-ol + H(+) + NADPH = 5alpha-
CC cholest-8-en-3beta-ol + NADP(+); Xref=Rhea:RHEA:46456,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16608, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:86131;
CC Evidence={ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:16784888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP(+) =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + H(+) + NADPH;
CC Xref=Rhea:RHEA:18561, ChEBI:CHEBI:15378, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.70;
CC Evidence={ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:9630650};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-8,14-cholestadien-3beta-ol + H(+) + NADPH = 4,4-
CC dimethyl-5alpha-cholest-8-en-3beta-ol + NADP(+);
CC Xref=Rhea:RHEA:46812, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78904, ChEBI:CHEBI:87044;
CC Evidence={ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:16784888,
CC ECO:0000269|PubMed:9630650};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC -!- SUBUNIT: Interacts with CBX5 (PubMed:9169472, PubMed:15882967).
CC Interacts with DNA (PubMed:8157662). Interaction with DNA is sequence
CC independent with higher affinity for supercoiled and relaxed circular
CC DNA than linear DNA (PubMed:8157662). Interacts with lamin B
CC (PubMed:8157662). Interacts with CLNK (PubMed:26009488).
CC {ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:26009488,
CC ECO:0000269|PubMed:8157662, ECO:0000269|PubMed:9169472}.
CC -!- INTERACTION:
CC Q14739; Q13185: CBX3; NbExp=4; IntAct=EBI-1055147, EBI-78176;
CC Q14739; P45973: CBX5; NbExp=4; IntAct=EBI-1055147, EBI-78219;
CC Q14739; P60033: CD81; NbExp=3; IntAct=EBI-1055147, EBI-712921;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:8157662}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21327084}. Cytoplasm {ECO:0000269|PubMed:21327084}.
CC Nucleus {ECO:0000269|PubMed:21327084}. Note=Nucleus; nuclear rim.
CC {ECO:0000269|PubMed:21327084}.
CC -!- TISSUE SPECIFICITY: Expressed in the bone marrow, liver, heart, adrenal
CC gland, lung, placenta and uterus (PubMed:16784888). Expressed in
CC osteoclasts and osteoblast-like cells (PubMed:21327084).
CC {ECO:0000269|PubMed:16784888, ECO:0000269|PubMed:21327084}.
CC -!- DOMAIN: The Tudor domain may not recognize methylation marks, but
CC rather bind unassembled free histone H3.
CC {ECO:0000250|UniProtKB:P23913}.
CC -!- PTM: Phosphorylated by CDK1 in mitosis when the inner nuclear membrane
CC breaks down into vesicles that dissociate from the lamina and the
CC chromatin. It is phosphorylated by different protein kinases in
CC interphase when the membrane is associated with these structures.
CC Phosphorylation of LBR and HP1 proteins may be responsible for some of
CC the alterations in chromatin organization and nuclear structure which
CC occur at various times during the cell cycle. Phosphorylated by SRPK1.
CC In late anaphase LBR is dephosphorylated, probably by PP1 and/or PP2A,
CC allowing reassociation with chromatin. {ECO:0000269|PubMed:10049757,
CC ECO:0000269|PubMed:21795390}.
CC -!- DISEASE: Pelger-Huet anomaly (PHA) [MIM:169400]: An autosomal dominant
CC inherited abnormality of granulocytes, characterized by abnormal ovoid
CC shape, reduced nuclear segmentation and an apparently looser chromatin
CC structure. {ECO:0000269|PubMed:14617022}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Greenberg dysplasia (GRBGD) [MIM:215140]: A rare autosomal
CC recessive chondrodystrophy characterized by early in utero lethality.
CC Affected fetuses typically present with fetal hydrops, short-limbed
CC dwarfism, and a marked disorganization of chondro-osseous
CC calcification, and ectopic ossification centers.
CC {ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:21327084,
CC ECO:0000269|PubMed:27336722}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Reynolds syndrome (REYNS) [MIM:613471]: A syndrome
CC specifically associating limited cutaneous systemic sclerosis and
CC primary biliary cirrhosis. It is characterized by liver disease,
CC telangiectasia, abrupt onset of digital paleness or cyanosis in
CC response to cold exposure or stress (Raynaud phenomenon), and variable
CC features of scleroderma. The liver disease is characterized by
CC pruritis, jaundice, hepatomegaly, increased serum alkaline phosphatase
CC and positive serum mitochondrial autoantibodies, all consistent with
CC primary biliary cirrhosis. {ECO:0000269|PubMed:20522425}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- DISEASE: Pelger-Huet anomaly with mild skeletal anomalies (PHASK)
CC [MIM:618019]: A disease characterized by abnormal nuclear shape and
CC chromatin organization in blood granulocytes, short stature, and mild
CC skeletal anomalies. Initial skeletal features may improve with age.
CC {ECO:0000269|PubMed:23824842, ECO:0000269|PubMed:25348816}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92751.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L25931; AAA59494.1; -; mRNA.
DR EMBL; L25941; AAA59495.1; -; Genomic_DNA.
DR EMBL; L25932; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25933; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25934; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25935; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25936; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25937; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25938; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25939; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; L25940; AAA59495.1; JOINED; Genomic_DNA.
DR EMBL; AB209514; BAD92751.1; ALT_INIT; mRNA.
DR EMBL; AK222834; BAD96554.1; -; mRNA.
DR EMBL; AK312258; BAG35190.1; -; mRNA.
DR EMBL; CH471098; EAW69741.1; -; Genomic_DNA.
DR EMBL; BC020079; AAH20079.1; -; mRNA.
DR CCDS; CCDS1545.1; -.
DR PIR; A53616; A53616.
DR RefSeq; NP_002287.2; NM_002296.3.
DR RefSeq; NP_919424.1; NM_194442.2.
DR RefSeq; XP_011542487.1; XM_011544185.2.
DR PDB; 2DIG; NMR; -; A=1-55.
DR PDBsum; 2DIG; -.
DR AlphaFoldDB; Q14739; -.
DR BMRB; Q14739; -.
DR SMR; Q14739; -.
DR BioGRID; 110122; 252.
DR DIP; DIP-5987N; -.
DR IntAct; Q14739; 75.
DR MINT; Q14739; -.
DR STRING; 9606.ENSP00000339883; -.
DR SwissLipids; SLP:000001239; -.
DR GlyGen; Q14739; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q14739; -.
DR PhosphoSitePlus; Q14739; -.
DR SwissPalm; Q14739; -.
DR BioMuta; LBR; -.
DR DMDM; 20141468; -.
DR EPD; Q14739; -.
DR jPOST; Q14739; -.
DR MassIVE; Q14739; -.
DR MaxQB; Q14739; -.
DR PaxDb; Q14739; -.
DR PeptideAtlas; Q14739; -.
DR PRIDE; Q14739; -.
DR ProteomicsDB; 60152; -.
DR TopDownProteomics; Q14739; -.
DR Antibodypedia; 34642; 245 antibodies from 31 providers.
DR DNASU; 3930; -.
DR Ensembl; ENST00000272163.9; ENSP00000272163.4; ENSG00000143815.15.
DR Ensembl; ENST00000338179.6; ENSP00000339883.2; ENSG00000143815.15.
DR GeneID; 3930; -.
DR KEGG; hsa:3930; -.
DR MANE-Select; ENST00000272163.9; ENSP00000272163.4; NM_002296.4; NP_002287.2.
DR UCSC; uc001hoy.4; human.
DR CTD; 3930; -.
DR DisGeNET; 3930; -.
DR GeneCards; LBR; -.
DR HGNC; HGNC:6518; LBR.
DR HPA; ENSG00000143815; Low tissue specificity.
DR MalaCards; LBR; -.
DR MIM; 169400; phenotype.
DR MIM; 215140; phenotype.
DR MIM; 600024; gene.
DR MIM; 613471; phenotype.
DR MIM; 618019; phenotype.
DR neXtProt; NX_Q14739; -.
DR OpenTargets; ENSG00000143815; -.
DR Orphanet; 1426; Greenberg dysplasia.
DR Orphanet; 448267; Regressive spondylometaphyseal dysplasia.
DR Orphanet; 779; Reynolds syndrome.
DR PharmGKB; PA30304; -.
DR VEuPathDB; HostDB:ENSG00000143815; -.
DR eggNOG; KOG1435; Eukaryota.
DR GeneTree; ENSGT00390000000417; -.
DR HOGENOM; CLU_015631_0_2_1; -.
DR InParanoid; Q14739; -.
DR OMA; SYWRVDT; -.
DR OrthoDB; 532774at2759; -.
DR PhylomeDB; Q14739; -.
DR TreeFam; TF101179; -.
DR BioCyc; MetaCyc:HS07110-MON; -.
DR BRENDA; 1.3.1.70; 2681.
DR PathwayCommons; Q14739; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR SignaLink; Q14739; -.
DR SIGNOR; Q14739; -.
DR UniPathway; UPA00063; -.
DR BioGRID-ORCS; 3930; 8 hits in 1084 CRISPR screens.
DR ChiTaRS; LBR; human.
DR EvolutionaryTrace; Q14739; -.
DR GeneWiki; Lamin_B_receptor; -.
DR GenomeRNAi; 3930; -.
DR Pharos; Q14739; Tbio.
DR PRO; PR:Q14739; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q14739; protein.
DR Bgee; ENSG00000143815; Expressed in trabecular bone tissue and 213 other tissues.
DR ExpressionAtlas; Q14739; baseline and differential.
DR Genevisible; Q14739; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; TAS:Reactome.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070087; F:chromo shadow domain binding; IPI:BHF-UCL.
DR GO; GO:0050613; F:delta14-sterol reductase activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0005521; F:lamin binding; TAS:ProtInc.
DR GO; GO:0070402; F:NADPH binding; IMP:UniProtKB.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030223; P:neutrophil differentiation; ISS:UniProtKB.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR CDD; cd04508; TUDOR; 1.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR019023; Lamin-B_rcpt_of_tudor.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR Pfam; PF09465; LBR_tudor; 1.
DR SMART; SM00333; TUDOR; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cholesterol biosynthesis;
KW Cholesterol metabolism; Cytoplasm; Disease variant; DNA-binding; Dwarfism;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Nucleus; Oxidoreductase; Phosphoprotein; Receptor; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..615
FT /note="Delta(14)-sterol reductase LBR"
FT /id="PRO_0000207510"
FT TOPO_DOM 1..211
FT /note="Nuclear"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 386..406
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 561..581
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 1..62
FT /note="Tudor"
FT REGION 52..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..75
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..90
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3U9G9"
FT MOD_RES 71
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:21795390"
FT MOD_RES 86
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:21795390"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 118
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 594
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 601
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 76..615
FT /note="Missing (in PHASK; dbSNP:rs869312905)"
FT /evidence="ECO:0000269|PubMed:25348816"
FT /id="VAR_081005"
FT VARIANT 119
FT /note="P -> L (in PHA; dbSNP:rs137852605)"
FT /evidence="ECO:0000269|PubMed:14617022"
FT /id="VAR_017841"
FT VARIANT 154
FT /note="S -> N (in dbSNP:rs2230419)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:8157663, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.5, ECO:0000269|Ref.6"
FT /id="VAR_024318"
FT VARIANT 169
FT /note="R -> C (in dbSNP:rs2230420)"
FT /id="VAR_052155"
FT VARIANT 311
FT /note="T -> A (in dbSNP:rs2275601)"
FT /id="VAR_020209"
FT VARIANT 372
FT /note="R -> C (in REYNS; dbSNP:rs200180113)"
FT /evidence="ECO:0000269|PubMed:20522425"
FT /id="VAR_063811"
FT VARIANT 547
FT /note="N -> D (in GRBGD; significant reduction in affinity
FT for NADPH; loss of cholesterol biosynthesis; does not
FT affect protein stability; dbSNP:rs587777171)"
FT /evidence="ECO:0000269|PubMed:21327084,
FT ECO:0000269|PubMed:27336722"
FT /id="VAR_081220"
FT VARIANT 547
FT /note="N -> S (in PHASK; unknown pathological significance;
FT dbSNP:rs374343844)"
FT /evidence="ECO:0000269|PubMed:25348816"
FT /id="VAR_081006"
FT VARIANT 569
FT /note="P -> R (in PHA; dbSNP:rs137852606)"
FT /evidence="ECO:0000269|PubMed:14617022"
FT /id="VAR_017842"
FT VARIANT 583
FT /note="R -> Q (in GRBGD; significant reduction in affinity
FT for NADPH; loss of cholesterol biosynthesis; does not
FT affect protein stability; dbSNP:rs587777172)"
FT /evidence="ECO:0000269|PubMed:21327084,
FT ECO:0000269|PubMed:27336722"
FT /id="VAR_081221"
FT VARIANT 586
FT /note="R -> H (in PHASK; unknown pathological significance;
FT dbSNP:rs573510559)"
FT /evidence="ECO:0000269|PubMed:23824842"
FT /id="VAR_081007"
FT CONFLICT 301
FT /note="A -> P (in Ref. 1; AAA59494)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="F -> L (in Ref. 5; BAD96554)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="T -> S (in Ref. 1; AAA59494)"
FT /evidence="ECO:0000305"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:2DIG"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:2DIG"
FT STRAND 22..31
FT /evidence="ECO:0007829|PDB:2DIG"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:2DIG"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:2DIG"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:2DIG"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2DIG"
SQ SEQUENCE 615 AA; 70703 MW; 5A7388776F43C66D CRC64;
MPSRKFADGE VVRGRWPGSS LYYEVEILSH DSTSQLYTVK YKDGTELELK ENDIKPLTSF
RQRKGGSTSS SPSRRRGSRS RSRSRSPGRP PKSARRSASA SHQADIKEAR REVEVKLTPL
ILKPFGNSIS RYNGEPEHIE RNDAPHKNTQ EKFSLSQESS YIATQYSLRP RREEVKLKEI
DSKEEKYVAK ELAVRTFEVT PIRAKDLEFG GVPGVFLIMF GLPVFLFLLL LMCKQKDPSL
LNFPPPLPAL YELWETRVFG VYLLWFLIQV LFYLLPIGKV VEGTPLIDGR RLKYRLNGFY
AFILTSAVIG TSLFQGVEFH YVYSHFLQFA LAATVFCVVL SVYLYMRSLK APRNDLSPAS
SGNAVYDFFI GRELNPRIGT FDLKYFCELR PGLIGWVVIN LVMLLAEMKI QDRAVPSLAM
ILVNSFQLLY VVDALWNEEA LLTTMDIIHD GFGFMLAFGD LVWVPFIYSF QAFYLVSHPN
EVSWPMASLI IVLKLCGYVI FRGANSQKNA FRKNPSDPKL AHLKTIHTST GKNLLVSGWW
GFVRHPNYLG DLIMALAWSL PCGFNHILPY FYIIYFTMLL VHREARDEYH CKKKYGVAWE
KYCQRVPYRI FPYIY
