LBR_PONAB
ID LBR_PONAB Reviewed; 615 AA.
AC Q5R7H4;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 76.
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=Sterol C14-reductase;
GN Name=LBR;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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; CR860142; CAH92286.1; -; mRNA.
DR RefSeq; NP_001127533.1; NM_001134061.1.
DR AlphaFoldDB; Q5R7H4; -.
DR BMRB; Q5R7H4; -.
DR SMR; Q5R7H4; -.
DR STRING; 9601.ENSPPYP00000000176; -.
DR GeneID; 100174610; -.
DR KEGG; pon:100174610; -.
DR CTD; 3930; -.
DR eggNOG; KOG1435; Eukaryota.
DR InParanoid; Q5R7H4; -.
DR OrthoDB; 532774at2759; -.
DR UniPathway; UPA00063; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0006695; P:cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030223; P:neutrophil differentiation; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW DNA-binding; Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Nucleus; Oxidoreductase; Phosphoprotein; Receptor;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..615
FT /note="Delta(14)-sterol reductase LBR"
FT /id="PRO_0000227910"
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 415..435
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 53..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:0000250|UniProtKB:Q14739"
FT MOD_RES 58
FT /note="Phosphothreonine"
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|UniProtKB:Q14739"
FT MOD_RES 97
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 118
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 594
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
FT MOD_RES 601
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14739"
SQ SEQUENCE 615 AA; 70590 MW; 7840729DA0AF1D09 CRC64;
MPSRKFADGE VVRGRWPGSS LYYEVEILSH DSASQLYTVK YKDGTELELK ENDIKPLTSF
RQRKGGSTSS SPSRRRGSRS RSRSRSPGRP PKSARRSASA SHQADIKEAR REVEVKLTPL
ILKPFGNSIS RYNGEPEHIE RNDVPHKNTQ EKFNLSQESS YIATQCSLRP KREEVKLKEI
DSKEEKFVAK ELAVRTFEVT PIRAKDLEFG GVPGVFLIMF GLPVFLFLLL LMCKQKDPSL
LNFPPPLPAL YELWETRVFG VYLLWFLIQV VFYLLPIGKV VEGTPLIDGR RLKYRLNGFY
AFILTSAVIG TSLFQGVEFH YVYSHFLQFA LAATVFCVVL SVYLYMRSLK APRNDLSPAS
SGNAVYDFFI GRELNPRIGT FDLKYFCELR PGLIGWVVIN LVMLLAEMKI QDRAVPSLAM
ILVNSFQLLY VVDALWNEEA LLTTMDIIHD GFGFMLAFGD LVWVPFIYSF QAFYLVSHPN
EVSWPMASLI IVLKFCGYVI FRGANSQKNA FRKNPSDPKL AHLKTIHTST GKNLLVSGWW
GFARHPNYLG DLIMALAWSL ACGFNHILPY FYIIYFTMLL VHREARDEYH CKKKYGVAWE
KYCQRVPYRI FPYIY
