NR5A2_RAT
ID NR5A2_RAT Reviewed; 560 AA.
AC Q9QWM1; Q9QWM0;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Nuclear receptor subfamily 5 group A member 2;
DE AltName: Full=FTZ-F1 beta;
DE AltName: Full=Liver receptor homolog 1;
DE Short=LRH-1;
GN Name=Nr5a2;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Liver;
RA Yanase T., Ichino I., Oba K.;
RT "Rat FTZ-F1beta1 (rat homologue 1 of mLRH-1).";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC {ECO:0000250|UniProtKB:O00482, ECO:0000250|UniProtKB:P45448}.
CC -!- SUBUNIT: Binds DNA as a monomer (By similarity). Interacts with GRIP1,
CC NCOA2 and NR0B2. Interacts (when sumoylated) with GPS2; interaction
CC with GPS2 onto hepatic acute phase protein promoters prevents N-Cor
CC corepressor complex dissociation (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O00482}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=FTZ-F1 beta1;
CC IsoId=Q9QWM1-1; Sequence=Displayed;
CC Name=2; Synonyms=FTZ-F1 beta2;
CC IsoId=Q9QWM1-2; Sequence=VSP_017915;
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}.
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DR EMBL; AB012960; BAA36339.1; -; mRNA.
DR EMBL; AB012961; BAA36340.1; -; mRNA.
DR RefSeq; NP_068510.1; NM_021742.1. [Q9QWM1-1]
DR RefSeq; XP_006249990.1; XM_006249928.3. [Q9QWM1-2]
DR AlphaFoldDB; Q9QWM1; -.
DR SMR; Q9QWM1; -.
DR STRING; 10116.ENSRNOP00000000812; -.
DR PhosphoSitePlus; Q9QWM1; -.
DR Ensembl; ENSRNOT00000000812; ENSRNOP00000000812; ENSRNOG00000000653. [Q9QWM1-1]
DR Ensembl; ENSRNOT00000097279; ENSRNOP00000096873; ENSRNOG00000000653. [Q9QWM1-2]
DR GeneID; 60349; -.
DR KEGG; rno:60349; -.
DR UCSC; RGD:68353; rat. [Q9QWM1-1]
DR CTD; 2494; -.
DR RGD; 68353; Nr5a2.
DR eggNOG; KOG4218; Eukaryota.
DR GeneTree; ENSGT00940000153391; -.
DR HOGENOM; CLU_011437_0_0_1; -.
DR InParanoid; Q9QWM1; -.
DR OMA; FLMVEWA; -.
DR OrthoDB; 619653at2759; -.
DR PhylomeDB; Q9QWM1; -.
DR TreeFam; TF350737; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR PRO; PR:Q9QWM1; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000000653; Expressed in ovary and 10 other tissues.
DR Genevisible; Q9QWM1; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:RGD.
DR GO; GO:0005543; F:phospholipid binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0090425; P:acinar cell differentiation; IEA:Ensembl.
DR GO; GO:0008206; P:bile acid metabolic process; ISO:RGD.
DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0061113; P:pancreas morphogenesis; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
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 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 2: Evidence at transcript level;
KW Activator; Alternative splicing; DNA-binding; Isopeptide bond;
KW Lipid-binding; Metal-binding; Nucleus; Receptor; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..560
FT /note="Nuclear receptor subfamily 5 group A member 2"
FT /id="PRO_0000232606"
FT DOMAIN 319..558
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 104..179
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..162
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 17..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 176..205
FT /note="FTZ-F1 box"
FT /evidence="ECO:0000250"
FT COMPBIAS 31..54
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 VAR_SEQ 22..43
FT /note="APAPGSETPHSPKLEEKHREKR -> G (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_017915"
SQ SEQUENCE 560 AA; 63904 MW; F738B943B443CCE2 CRC64;
MSASSITGDF QDFLKHGLPA IAPAPGSETP HSPKLEEKHR EKRAGLPDRH RRPIPARSRL
VMLPKVETEA SGLVRSHGEQ GQMPENMQVS QFKMVNYSYD EDLEELCPVC GDKVSGYHYG
LLTCESCKGF FKRTVQNQKR YTCIENQNCQ IDKTQRKRCP YCRFKKCIDV GMKLEAVRAD
RMRGGRNKFG PMYKRDRALK QQKKALIRAN GLKLEAMSQV IQAMPSDLTS AIQNIHSASK
GLPLSHVALP PTDYDRSPFV TSPISMTMPP HGSLHGYQPY GHFPNRAIKS EYPDPYSSSP
ESMMGYSYMD GYQTSSPASI PHLILELLKC EPDEPQVQAK IMAYLQQEQN NRNRQEKLSA
FGLLCKMADQ TLFSIVEWAR SSIFFRELKV DDQMKLLQNC WSELLILDHI YRQVAHGKEG
TIFLVTGEHV DYSSIISNTE VAFNNLLSLA QELVVRLRSL QFDQREFVCL KFLVLFSSDV
KNLENFQLVE GVQEQVNAAL LDYTLCNYPQ QTEKFGQLLL RLPEIRAISK QAEDYLYYKH
VNGDVPYNNL LIEMLHAKRA