NR5A2_MOUSE
ID NR5A2_MOUSE Reviewed; 560 AA.
AC P45448; B9EHF9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Nuclear receptor subfamily 5 group A member 2;
DE AltName: Full=Liver receptor homolog 1;
DE Short=LRH-1;
GN Name=Nr5a2; Synonyms=Lrh1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tugwood J.D., Issemann I., Green S.;
RT "LRH-1: a nuclear hormone receptor active in the absence of exogenous
RT ligands.";
RL Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP FUNCTION.
RX PubMed=30555544; DOI=10.7150/thno.28676;
RA Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT induced hepatotoxicity.";
RL Theranostics 8:5246-5258(2018).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 313-560, AND INTERACTION WITH
RP NR0B2 AND GRIP1.
RX PubMed=12820970; DOI=10.1016/s1097-2765(03)00236-3;
RA Sablin E.P., Krylova I.N., Fletterick R.J., Ingraham H.A.;
RT "Structural basis for ligand-independent activation of the orphan nuclear
RT receptor LRH-1.";
RL Mol. Cell 11:1575-1585(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 318-560 IN COMPLEX WITH NR0B2.
RX PubMed=15976031; DOI=10.1073/pnas.0501204102;
RA Li Y., Choi M., Suino K., Kovach A., Daugherty J., Kliewer S.A., Xu H.E.;
RT "Structural and biochemical basis for selective repression of the orphan
RT nuclear receptor liver receptor homolog 1 by small heterodimer partner.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9505-9510(2005).
CC -!- FUNCTION: Nuclear receptor that acts as a key metabolic sensor by
CC regulating the expression of genes involved in bile acid synthesis,
CC cholesterol homeostasis and triglyceride synthesis. Together with the
CC oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an
CC essential transcriptional regulator of lipid metabolism. Plays an anti-
CC inflammatory role during the hepatic acute phase response by acting as
CC a corepressor: inhibits the hepatic acute phase response by preventing
CC dissociation of the N-Cor corepressor complex. Key regulator of
CC cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May
CC also contribute to the regulation of pancreas-specific genes and play
CC important roles in embryonic development (By similarity). Activates the
CC transcription of CYP2C38 (PubMed:30555544).
CC {ECO:0000250|UniProtKB:O00482, ECO:0000269|PubMed:30555544}.
CC -!- SUBUNIT: Binds DNA as a monomer (By similarity). Interacts with GRIP1,
CC NCOA2 and NR0B2 (PubMed:12820970, PubMed:15976031). Interacts (when
CC sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase
CC protein promoters prevents N-Cor corepressor complex dissociation (By
CC similarity). {ECO:0000250|UniProtKB:O00482,
CC ECO:0000269|PubMed:12820970, ECO:0000269|PubMed:15976031}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O00482}.
CC -!- PTM: Sumoylated by SUMO1 at Lys-289 during the hepatic acute phase
CC response, leading to promote interaction with GPS2 and prevent N-Cor
CC corepressor complex dissociation. {ECO:0000250|UniProtKB:O00482}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR5
CC subfamily. {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; M81385; AAA39447.1; -; mRNA.
DR EMBL; BC137845; AAI37846.1; -; mRNA.
DR CCDS; CCDS15328.1; -.
DR PIR; S27874; S27874.
DR RefSeq; NP_109601.1; NM_030676.3.
DR PDB; 1PK5; X-ray; 2.40 A; A/B=313-560.
DR PDB; 1ZH7; X-ray; 2.50 A; A/B=318-560.
DR PDB; 3F5C; X-ray; 3.00 A; A=313-560.
DR PDBsum; 1PK5; -.
DR PDBsum; 1ZH7; -.
DR PDBsum; 3F5C; -.
DR AlphaFoldDB; P45448; -.
DR SMR; P45448; -.
DR BioGRID; 204976; 3.
DR STRING; 10090.ENSMUSP00000027649; -.
DR iPTMnet; P45448; -.
DR PhosphoSitePlus; P45448; -.
DR MaxQB; P45448; -.
DR PaxDb; P45448; -.
DR PRIDE; P45448; -.
DR ProteomicsDB; 293888; -.
DR Antibodypedia; 1690; 491 antibodies from 40 providers.
DR DNASU; 26424; -.
DR Ensembl; ENSMUST00000027649; ENSMUSP00000027649; ENSMUSG00000026398.
DR GeneID; 26424; -.
DR KEGG; mmu:26424; -.
DR UCSC; uc007cva.2; mouse.
DR CTD; 2494; -.
DR MGI; MGI:1346834; Nr5a2.
DR VEuPathDB; HostDB:ENSMUSG00000026398; -.
DR eggNOG; KOG4218; Eukaryota.
DR GeneTree; ENSGT00940000153391; -.
DR InParanoid; P45448; -.
DR OrthoDB; 619653at2759; -.
DR PhylomeDB; P45448; -.
DR TreeFam; TF350737; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR BioGRID-ORCS; 26424; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Nr5a2; mouse.
DR EvolutionaryTrace; P45448; -.
DR PRO; PR:P45448; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P45448; protein.
DR Bgee; ENSMUSG00000026398; Expressed in cumulus cell and 145 other tissues.
DR ExpressionAtlas; P45448; baseline and differential.
DR Genevisible; P45448; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0090425; P:acinar cell differentiation; IMP:MGI.
DR GO; GO:0008206; P:bile acid metabolic process; IMP:MGI.
DR GO; GO:0097720; P:calcineurin-mediated signaling; ISO:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:MGI.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0061113; P:pancreas morphogenesis; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID50211; -.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR016355; NR5_fam.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR24086; PTHR24086; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PIRSF; PIRSF002530; Nuc_orph_FTZ-F1; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Isopeptide bond; Lipid-binding;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..560
FT /note="Nuclear receptor subfamily 5 group A member 2"
FT /id="PRO_0000053736"
FT DOMAIN 319..558
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 104..175
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 107..127
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 143..167
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 21..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 176..205
FT /note="FTZ-F1 box"
FT COMPBIAS 29..55
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 535
FT /ligand="a phosphatidylglycerol phosphate"
FT /ligand_id="ChEBI:CHEBI:60522"
FT /evidence="ECO:0000250|UniProtKB:O00482"
FT BINDING 539
FT /ligand="a phosphatidylglycerol phosphate"
FT /ligand_id="ChEBI:CHEBI:60522"
FT /evidence="ECO:0000250|UniProtKB:O00482"
FT CROSSLNK 289
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:O00482"
FT HELIX 322..329
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 334..351
FT /evidence="ECO:0007829|PDB:1PK5"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 361..381
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 390..416
FT /evidence="ECO:0007829|PDB:1PK5"
FT STRAND 419..423
FT /evidence="ECO:0007829|PDB:1PK5"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 432..437
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 441..459
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 464..475
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 486..507
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 514..519
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 522..541
FT /evidence="ECO:0007829|PDB:1PK5"
FT HELIX 549..555
FT /evidence="ECO:0007829|PDB:1PK5"
FT TURN 556..558
FT /evidence="ECO:0007829|PDB:1PK5"
SQ SEQUENCE 560 AA; 64020 MW; 186F8C4025934643 CRC64;
MSASLDTGDF QEFLKHGLTA IASAPGSETR HSPKREEQLR EKRAGLPDRH RRPIPARSRL
VMLPKVETEA PGLVRSHGEQ GQMPENMQVS QFKMVNYSYD EDLEELCPVC GDKVSGYHYG
LLTCESCKGF FKRTVQNQKR YTCIENQNCQ IDKTQRKRCP YCRFKKCIDV GMKLEAVRAD
RMRGGRNKFG PMYKRDRALK QQKKALIRAN GLKLEAMSQV IQAMPSDLTS AIQNIHSASK
GLPLSHVALP PTDYDRSPFV TSPISMTMPP HSSLHGYQPY GHFPSRAIKS EYPDPYSSSP
ESMMGYSYMD GYQTNSPASI PHLILELLKC EPDEPQVQAK IMAYLQQEQS NRNRQEKLSA
FGLLCKMADQ TLFSIVEWAR SSIFFRELKV DDQMKLLQNC WSELLILDHI YRQVAHGKEG
TIFLVTGEHV DYSTIISHTE VAFNNLLSLA QELVVRLRSL QFDQREFVCL KFLVLFSSDV
KNLENLQLVE GVQEQVNAAL LDYTVCNYPQ QTEKFGQLLL RLPEIRAISK QAEDYLYYKH
VNGDVPYNNL LIEMLHAKRA
