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UniProtKB/Swiss-Prot entry Q14739


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name LBR_HUMAN
Primary accession number Q14739
Secondary accession numbers Q14740 Q53GU7 Q59FE6
Integrated into Swiss-Prot on November 1, 1997
Sequence was last modified on January 31, 2002 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 95)
Name and origin of the protein
Protein name Lamin-B receptor
Synonyms Integral nuclear envelope inner membrane protein
LMN2R
Gene name
Name: LBR
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH DNA; LMNB1 AND LMNB2.
PubMed=8157662 [NCBI, ExPASy, EBI, Israel, Japan]
Ye Q., Worman H.J.;
"Primary structure analysis and lamin B and DNA binding of human LBR, an integral protein of the nuclear envelope inner membrane.";
J. Biol. Chem. 269:11306-11311(1994).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-154.
PubMed=8157663 [NCBI, ExPASy, EBI, Israel, Japan]
Schuler E., Lin F., Worman H.J.;
"Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane.";
J. Biol. Chem. 269:11312-11317(1994).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-154.
TISSUE=Brain;
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-154.
TISSUE=Liver;
Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Skin;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
SUBUNIT, AND INTERACTION WITH CBX5.
DOI=10.1074/jbc.272.23.14983; PubMed=9169472 [NCBI, ExPASy, EBI, Israel, Japan]
Ye Q., Callebaut I., Pezhman A., Courvalin J.-C., Worman H.J.;
"Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR.";
J. Biol. Chem. 272:14983-14989(1997).
[7]
FUNCTION.
DOI=10.1021/bi992908b; PubMed=10828963 [NCBI, ExPASy, EBI, Israel, Japan]
Duband-Goulet I., Courvalin J.-C.;
"Inner nuclear membrane protein LBR preferentially interacts with DNA secondary structures and nucleosomal linker.";
Biochemistry 39:6483-6488(2000).
[8]
DISEASE.
DOI=10.1038/ng925; PubMed=12118250 [NCBI, ExPASy, EBI, Israel, Japan]
Hoffmann K., Dreger C.K., Olins A.L., Olins D.E., Shultz L.D., Lucke B., Karl H., Kaps R., Mueller D., Vaya A., Aznar J., Ware R.E., Sotelo Cruz N., Lindner T.H., Herrmann H., Reis A., Sperling K.;
"Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huet anomaly).";
Nat. Genet. 31:410-414(2002).
[9]
DISEASE.
DOI=10.1086/373938; PubMed=12618959 [NCBI, ExPASy, EBI, Israel, Japan]
Waterham H.R., Koster J., Mooyer P., van Noort G., Kelley R.I., Wilcox W.R., Wanders R.J., Hennekam R.C.M., Oosterwijk J.C.;
"Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene.";
Am. J. Hum. Genet. 72:1013-1017(2003).
[10]
SUBUNIT, AND INTERACTION WITH CBX5.
DOI=10.1016/j.bbrc.2005.04.016; PubMed=15882967 [NCBI, ExPASy, EBI, Israel, Japan]
Lechner M.S., Schultz D.C., Negorev D., Maul G.G., Rauscher F.J. III;
"The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain.";
Biochem. Biophys. Res. Commun. 331:929-937(2005).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1021/pr070152u; PubMed=17924679 [NCBI, ExPASy, EBI, Israel, Japan]
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.";
J. Proteome Res. 6:4150-4162(2007).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[13]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[14]
STRUCTURE BY NMR OF 1-55.
RIKEN structural genomics initiative (RSGI);
"Solusion structure of the Tudor domain of human lamin-B receptor.";
Submitted (SEP-2006) to the PDB data bank.
[15]
VARIANTS PHA LEU-119 AND ARG-569.
DOI=10.1046/j.1365-2141.2003.04621.x; PubMed=14617022 [NCBI, ExPASy, EBI, Israel, Japan]
Best S., Salvati F., Kallo J., Garner C., Height S., Thein S.L., Rees D.C.;
"Lamin B-receptor mutations in Pelger-Huet anomaly.";
Br. J. Haematol. 123:542-544(2003).
Comments
  • FUNCTION: Anchors the lamina and the heterochromatin to the inner nuclear membrane.
  • SUBUNIT: Interacts directly with CBX5. Can interact with chromodomain proteins. Interacts directly with DNA. Interaction with DNA is sequence independent with higher affinity for supercoiled and relaxed circular DNA than linear DNA.
  • INTERACTION:
    Q13185:CBX3; NbExp=1; IntAct=EBI-1055147, EBI-78176;
    P45973:CBX5; NbExp=1; IntAct=EBI-1055147, EBI-78219;
    P61981:YWHAG; NbExp=1; IntAct=EBI-1055147, EBI-359832;
  • SUBCELLULAR LOCATION: Nucleus inner membrane; Multi-pass membrane protein.
  • PTM: Phosphorylated by CDC2 protein kinase in mitosis when the inner nuclear membrane breaks down into vesicles that dissociate from the lamina and the chromatin. It is phosphorylated by different protein kinases in interphase when the membrane is associated with these structures. Phosphorylation of LBR and HP1 proteins may be responsible for some of the alterations in chromatin organization and nuclear structure which occur at various times during the cell cycle.
  • DISEASE: Defects in LBR are a cause of Pelger-Huet anomaly (PHA) [MIM:169400]. PHA is an autosomal dominant inherited abnormality of neutrophils, characterized by reduced nuclear segmentation and an apparently looser chromatin structure. Heterozygotes show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy, and skeletal abnormalities.
  • DISEASE: Defects in LBR are the cause of hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM) [MIM:215140]; also known as Greenberg skeletal dysplasia. HEM is a rare autosomal recessive chondrodystrophy characterized by early in utero lethality and, therefore, considered to be nonviable. Affected fetuses typically present with fetal hydrops, short-limbed dwarfism, and a marked disorganization of chondro-osseous calcification and may present with polydactyly and additional nonskeletal malformations.
  • SIMILARITY: Belongs to the ERG4/ERG24 family.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=LBR";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L25931; AAA59494.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25941; AAA59495.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25932; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25933; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25934; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25935; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25936; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25937; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25938; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25939; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L25940; AAA59495.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB209514; BAD92751.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK222834; BAD96554.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC020079; AAH20079.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00292135; -.
PIR A53616; A53616.
RefSeq NP_002287.2; -.
NP_919424.1; -.
UniGene Hs.435166
3D structure databases
PDB
2DIG; NMR; -; A=1-55.[ExPASy / RCSB / EBI]
PDBsum 2DIG; -.
ModBase Q14739.
Protein-protein interaction databases
DIP DIP:5987N; -.
IntAct Q14739; 7.
PTM databases
PhosphoSite Q14739; -.
Enzyme and pathway databases
BRENDA 1.3.1.70; 247.
Reactome REACT_602; Lipid and lipoprotein metabolism.
Organism-specific databases
GeneCards GC01M223657; -.
H-InvDB HIX0001633; -.
HIX0028542; -.
HGNC HGNC:6518; LBR.
GenAtlas LBR.
MIM 169400; phenotype. [NCBI / EBI]
215140; phenotype. [NCBI / EBI]
600024; gene. [NCBI / EBI]
Orphanet 1426; Greenberg dysplasia.
PharmGKB PA30304; -.
Gene expression databases
ArrayExpress Q14739; -.
Bgee Q14739; -.
CleanEx HS_LBR; -.
GermOnline ENSG00000143815; Homo sapiens.
Ontologies
GO
GO:0005639; Cellular component: integral to nuclear inner membrane (traceable author statement from ProtInc).
GO:0050613; Molecular function: delta14-sterol reductase activity (inferred from experiment from Reactome).
GO:0003677; Molecular function: DNA binding (traceable author statement from ProtInc).
GO:0005521; Molecular function: lamin binding (traceable author statement from ProtInc).
GO:0004872; Molecular function: receptor activity (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR001171; Ergosterol_biosynth_ERG4_ERG24.
IPR019023; Lamin-B_rcpt_of_tudor.
IPR018083; Sterol_reductase_CS.
IPR002999; Tudor.
Graphical view of domain structure.
Pfam PF01222; ERG4_ERG24; 1.
PF09465; LBR_tudor; 1.
Pfam graphical view of domain structure.
SMART SM00333; TUDOR; 1.
SMART graphical view of domain structure.
PROSITE PS01017; STEROL_REDUCT_1; 1.
PS01018; STEROL_REDUCT_2; 1.
Proteomic databases
PeptideAtlas Q14739; -.
PRIDE Q14739; -.
Genome annotation databases
Ensembl ENSG00000143815; Homo sapiens. [Contig view]
GeneID 3930; -.
KEGG hsa:3930; -.
Phylogenomic databases
HOGENOM Q14739; -.
HOVERGEN Q14739; -.
OMA Q14739; YVVDALW.
Other
NextBio 15431; -.
SOURCE LBR; Homo sapiens.
ProtoNet Q14739.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Disease mutation; DNA-binding; Membrane; Nucleus; Phosphoprotein; Polymorphism; Receptor; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   615  615     Lamin-B receptor. PRO_0000207510
TRANSMEM   212   232  21     Potential. 
TRANSMEM   258   278  21     Potential. 
TRANSMEM   299   319  21     Potential. 
TRANSMEM   326   346  21     Potential. 
TRANSMEM   386   406  21     Potential. 
TRANSMEM   447   467  21     Potential. 
TRANSMEM   481   501  21     Potential. 
TRANSMEM   561   581  21     Potential. 
REGION   1   208  208     Nucleoplasmic (Potential). 
MOD_RES   99    99        Phosphoserine. 
MOD_RES   118   118        Phosphothreonine. 
VARIANT   119   119  1     P -> L (in PHA). VAR_017841 
VARIANT   154   154  1     S -> N (in dbSNP:rs2230419 [NCBI]). VAR_024318 
VARIANT   169   169  1     R -> C (in dbSNP:rs2230420 [NCBI]). VAR_052155 
VARIANT   311   311  1     T -> A (in dbSNP:rs2275601 [NCBI]). VAR_020209 
VARIANT   569   569  1     P -> R (in PHA). VAR_017842 
CONFLICT   301   301        A -> P (in Ref. 1; AAA59494). 
CONFLICT   452   452        F -> L (in Ref. 4; BAD96554). 
CONFLICT   530   530        T -> S (in Ref. 1; AAA59494). 
Sequence information
Length: 615 AA [This is the length of the unprocessed precursor] Molecular weight: 70703 Da [This is the MW of the unprocessed precursor] CRC64: 5A7388776F43C66D [This is a checksum on the sequence]
        10         20         30         40         50         60 
MPSRKFADGE VVRGRWPGSS LYYEVEILSH DSTSQLYTVK YKDGTELELK ENDIKPLTSF 

        70         80         90        100        110        120 
RQRKGGSTSS SPSRRRGSRS RSRSRSPGRP PKSARRSASA SHQADIKEAR REVEVKLTPL 

       130        140        150        160        170        180 
ILKPFGNSIS RYNGEPEHIE RNDAPHKNTQ EKFSLSQESS YIATQYSLRP RREEVKLKEI 

       190        200        210        220        230        240 
DSKEEKYVAK ELAVRTFEVT PIRAKDLEFG GVPGVFLIMF GLPVFLFLLL LMCKQKDPSL 

       250        260        270        280        290        300 
LNFPPPLPAL YELWETRVFG VYLLWFLIQV LFYLLPIGKV VEGTPLIDGR RLKYRLNGFY 

       310        320        330        340        350        360 
AFILTSAVIG TSLFQGVEFH YVYSHFLQFA LAATVFCVVL SVYLYMRSLK APRNDLSPAS 

       370        380        390        400        410        420 
SGNAVYDFFI GRELNPRIGT FDLKYFCELR PGLIGWVVIN LVMLLAEMKI QDRAVPSLAM 

       430        440        450        460        470        480 
ILVNSFQLLY VVDALWNEEA LLTTMDIIHD GFGFMLAFGD LVWVPFIYSF QAFYLVSHPN 

       490        500        510        520        530        540 
EVSWPMASLI IVLKLCGYVI FRGANSQKNA FRKNPSDPKL AHLKTIHTST GKNLLVSGWW 

       550        560        570        580        590        600 
GFVRHPNYLG DLIMALAWSL PCGFNHILPY FYIIYFTMLL VHREARDEYH CKKKYGVAWE 

       610 
KYCQRVPYRI FPYIY 

Q14739 in FASTA format

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