LBR_RAT
ID LBR_RAT Reviewed; 620 AA.
AC O08984;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Delta(14)-sterol reductase LBR;
DE Short=Delta-14-SR;
DE EC=1.3.1.70 {ECO:0000250|UniProtKB:Q14739};
DE AltName: Full=3-beta-hydroxysterol Delta (14)-reductase {ECO:0000250|UniProtKB:Q14739};
DE AltName: Full=C-14 sterol reductase;
DE Short=C14SR;
DE AltName: Full=Integral nuclear envelope inner membrane protein {ECO:0000250|UniProtKB:Q14739};
DE AltName: Full=Lamin-B receptor {ECO:0000250|UniProtKB:Q14739};
DE AltName: Full=NBP60 {ECO:0000303|PubMed:9192729};
DE AltName: Full=Sterol C14-reductase;
GN Name=Lbr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344; TISSUE=Liver;
RX PubMed=9192729; DOI=10.1093/oxfordjournals.jbchem.a021669;
RA Kawahire S., Takeuchi M., Gohshi T., Sasagawa S., Shimada M., Takahashi M.,
RA Abe T.K., Ueda T., Kuwano R., Hikawa A., Ichimura T., Omata S.,
RA Horigome T.;
RT "cDNA cloning of nuclear localization signal binding protein NBP60, a rat
RT homologue of lamin B receptor, and identification of binding sites of human
RT lamin B receptor for nuclear localization signals and chromatin.";
RL J. Biochem. 121:881-889(1997).
RN [2]
RP GLYCOSYLATION AT SER-96, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12438562; DOI=10.1074/mcp.m200048-mcp200;
RA Wells L., Vosseller K., Cole R.N., Cronshaw J.M., Matunis M.J., Hart G.W.;
RT "Mapping sites of O-GlcNAc modification using affinity tags for serine and
RT threonine post-translational modifications.";
RL Mol. Cell. Proteomics 1:791-804(2002).
RN [3]
RP SUBCELLULAR LOCATION.
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).
CC -!- FUNCTION: Catalyzes the reduction of the C14-unsaturated bond of
CC lanosterol, as part of the metabolic pathway leading to cholesterol
CC biosynthesis (By similarity). Plays a critical role in myeloid cell
CC cholesterol biosynthesis which is essential to both myeloid cell growth
CC and functional maturation (By similarity). Mediates the activation of
CC NADPH oxidases, perhaps by maintaining critical levels of cholesterol
CC required for membrane lipid raft formation during neutrophil
CC differentiation (By similarity). Anchors the lamina and the
CC heterochromatin to the inner nuclear membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q14739, ECO:0000250|UniProtKB:Q3U9G9}.
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:0000250|UniProtKB:Q14739};
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:0000250|UniProtKB:Q14739};
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:0000250|UniProtKB:Q14739};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC -!- SUBUNIT: Interacts with CBX5 (By similarity). Interacts with DNA (By
CC similarity). Interaction with DNA is sequence independent with higher
CC affinity for supercoiled and relaxed circular DNA than linear DNA (By
CC similarity). Interacts with lamin B (By similarity). Interacts with
CC CLNK (By similarity). {ECO:0000250|UniProtKB:Q14739}.
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000250|UniProtKB:Q14739}; Multi-pass membrane protein
CC {ECO:0000255}. Nucleus {ECO:0000250|UniProtKB:Q14739}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q14739}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q14739}. Note=Nucleus; nuclear rim.
CC {ECO:0000250|UniProtKB:Q14739}.
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 (By similarity). It is phosphorylated by different protein
CC kinases in interphase when the membrane is associated with these
CC structures (By similarity). Phosphorylation of LBR and HP1 proteins may
CC be responsible for some of the alterations in chromatin organization
CC and nuclear structure which occur at various times during the cell
CC cycle (By similarity). Phosphorylated by SRPK1 (By similarity). In late
CC anaphase LBR is dephosphorylated, probably by PP1 and/or PP2A, allowing
CC reassociation with chromatin (By similarity).
CC {ECO:0000250|UniProtKB:Q14739}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB002466; BAA20471.1; -; mRNA.
DR PIR; JC5567; JC5567.
DR RefSeq; NP_604448.1; NM_134453.1.
DR AlphaFoldDB; O08984; -.
DR SMR; O08984; -.
DR BioGRID; 250124; 3.
DR GlyGen; O08984; 1 site.
DR iPTMnet; O08984; -.
DR PhosphoSitePlus; O08984; -.
DR jPOST; O08984; -.
DR PRIDE; O08984; -.
DR GeneID; 89789; -.
DR KEGG; rno:89789; -.
DR UCSC; RGD:620813; rat.
DR CTD; 3930; -.
DR RGD; 620813; Lbr.
DR InParanoid; O08984; -.
DR OrthoDB; 532774at2759; -.
DR PhylomeDB; O08984; -.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR Reactome; R-RNO-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9022692; Regulation of MECP2 expression and activity.
DR UniPathway; UPA00063; -.
DR PRO; PR:O08984; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005635; C:nuclear envelope; IDA:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; ISO:RGD.
DR GO; GO:0005643; C:nuclear pore; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0051087; F:chaperone binding; IPI:RGD.
DR GO; GO:0070087; F:chromo shadow domain binding; ISO:RGD.
DR GO; GO:0050613; F:delta14-sterol reductase activity; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070402; F:NADPH binding; ISS:UniProtKB.
DR GO; GO:0008139; F:nuclear localization sequence binding; IPI:RGD.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IEP:RGD.
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 Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW DNA-binding; Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Nucleus; Oxidoreductase; Phosphoprotein;
KW Receptor; Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..620
FT /note="Delta(14)-sterol reductase LBR"
FT /id="PRO_0000227911"
FT TOPO_DOM 1..215
FT /note="Nuclear"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 331..351
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..506
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 525..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 566..586
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 1..62
FT /note="Tudor"
FT REGION 52..111
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..92
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
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:0000250|UniProtKB:Q14739"
FT MOD_RES 86
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 123
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 205
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 599
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 606
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT CARBOHYD 96
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:12438562"
SQ SEQUENCE 620 AA; 70724 MW; 04BD9FDDCC61ED5D CRC64;
MPGRKFADGE VVRGRWPGSS LYYEVEILSH DSTSQLYTVK YKDGTELELK ESDIKPLKSF
KQRKSGSTSS SPSRRRSSRS RSRSRSRSPG RAPKGSRRSV SASYQADAKE KEMRREILQV
KLTPLVLKPF ANSVSVYNGE PEHMEKSATP PKNKQERVIL STEDSYIATQ YSLRPRREEV
KPKHRVRGTN LVTRGPVPLG TFQVTTPQRR DLEFGGVPGA LLIMLGLPAC VFLLLLQCAQ
KDPGLLQFPP PLPALRELWE ARVCGVYLLW FFLQALFSLL PVGKVVEGTP LVDGRRLKYR
LNGLYAFILT SAAVGTAVFW DIELYYLYTH FLQFALAAIV FSVVLSVYLY ARSLKVPRDE
LSPASSGNAV YDFFIGRELN PRIGAFDLKF FCELRPGLIG WVVINLVMLL AEMKVQERSA
PSLAMTLVNS FQLLYVVDAL WFEEALLTTM DIIHDGFGFM LAFGDLVWVP FTYSLQAFYL
VNHPQDLSWP LTSVIIALKL CGYVIFRCAN SQKNAFRKNP TDPKLAHLKT IPTSTWKSLL
VSGWWGFVRH PNYLGDLIMA LAWSLPCGFN HILPYFYVIY FTALLIHREA RDEHQCRRKY
GLAWEKYCQR VPYRIFPYIY
