位置:首页 > 蛋白库 > NR1D1_BOVIN
NR1D1_BOVIN
ID   NR1D1_BOVIN             Reviewed;         613 AA.
AC   Q08E02;
DT   03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=Nuclear receptor subfamily 1 group D member 1;
DE   AltName: Full=Rev-erbA-alpha;
DE   AltName: Full=V-erbA-related protein 1;
DE            Short=EAR-1;
GN   Name=NR1D1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   INTERACTION WITH NR2E3.
RX   PubMed=15190009; DOI=10.1093/hmg/ddh173;
RA   Cheng H., Khanna H., Oh E.C., Hicks D., Mitton K.P., Swaroop A.;
RT   "Photoreceptor-specific nuclear receptor NR2E3 functions as a
RT   transcriptional activator in rod photoreceptors.";
RL   Hum. Mol. Genet. 13:1563-1575(2004).
CC   -!- FUNCTION: Transcriptional repressor which coordinates circadian rhythm
CC       and metabolic pathways in a heme-dependent manner. Integral component
CC       of the complex transcription machinery that governs circadian
CC       rhythmicity and forms a critical negative limb of the circadian clock
CC       by directly repressing the expression of core clock components
CC       ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic
CC       functions, including lipid and bile acid metabolism, adipogenesis,
CC       gluconeogenesis and the macrophage inflammatory response. Acts as a
CC       receptor for heme which stimulates its interaction with the NCOR1/HDAC3
CC       corepressor complex, enhancing transcriptional repression. Recognizes
CC       two classes of DNA response elements within the promoter of its target
CC       genes and can bind to DNA as either monomers or homodimers, depending
CC       on the nature of the response element. Binds as a monomer to a response
CC       element composed of the consensus half-site motif 5'-[A/G]GGTCA-3'
CC       preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a
CC       direct repeat of the core motif spaced by two nucleotides (RevDR-2).
CC       Acts as a potent competitive repressor of ROR alpha (RORA) function and
CC       regulates the levels of its ligand heme by repressing the expression of
CC       PPARGC1A, a potent inducer of heme synthesis. Regulates lipid
CC       metabolism by repressing the expression of APOC3 and by influencing the
CC       activity of sterol response element binding proteins (SREBPs);
CC       represses INSIG2 which interferes with the proteolytic activation of
CC       SREBPs which in turn govern the rhythmic expression of enzymes with key
CC       functions in sterol and fatty acid synthesis. Regulates gluconeogenesis
CC       via repression of G6PC1 and PEPCK and adipocyte differentiation via
CC       repression of PPARG. Regulates glucagon release in pancreatic alpha-
CC       cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-
CC       induced insulin secretion and expression of key lipogenic genes in
CC       pancreatic-beta cells. Positively regulates bile acid synthesis by
CC       increasing hepatic expression of CYP7A1 via repression of NR0B2 and
CC       NFIL3 which are negative regulators of CYP7A1. Modulates skeletal
CC       muscle oxidative capacity by regulating mitochondrial biogenesis and
CC       autophagy; controls mitochondrial biogenesis and respiration by
CC       interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway.
CC       Represses the expression of SERPINE1/PAI1, an important modulator of
CC       cardiovascular disease and the expression of inflammatory cytokines and
CC       chemokines in macrophages. Represses gene expression at a distance in
CC       macrophages by inhibiting the transcription of enhancer-derived RNAs
CC       (eRNAs). Plays a role in the circadian regulation of body temperature
CC       and negatively regulates thermogenic transcriptional programs in brown
CC       adipose tissue (BAT); imposes a circadian oscillation in BAT activity,
CC       increasing body temperature when awake and depressing thermogenesis
CC       during sleep. In concert with NR2E3, regulates transcriptional networks
CC       critical for photoreceptor development and function. In addition to its
CC       activity as a repressor, can also act as a transcriptional activator.
CC       In the ovarian granulosa cells acts as a transcriptional activator of
CC       STAR which plays a role in steroid biosynthesis. In collaboration with
CC       SP1, activates GJA1 transcription in a heme-independent manner (By
CC       similarity). Represses the transcription of CYP2B10, CYP4A10 and
CC       CYP4A14 (By similarity). Represses the transcription of CES2 (By
CC       similarity). Represses and regulates the circadian expression of TSHB
CC       in a NCOR1-dependent manner (By similarity). Negatively regulates the
CC       protein stability of NR3C1 and influences the time-dependent
CC       subcellular distribution of NR3C1, thereby affecting its
CC       transcriptional regulatory activity (By similarity). Plays a critical
CC       role in the circadian control of neutrophilic inflammation in the lung;
CC       under resting, non-stress conditions, acts as a rhythmic repressor to
CC       limit inflammatory activity whereas in the presence of inflammatory
CC       triggers undergoes ubiquitin-mediated degradation thereby relieving
CC       inhibition of the inflammatory response (By similarity). Plays a key
CC       role in the circadian regulation of microglial activation and
CC       neuroinflammation; suppresses microglial activation through the NF-
CC       kappaB pathway in the central nervous system (By similarity). Plays a
CC       role in the regulation of the diurnal rhythms of lipid and protein
CC       metabolism in the skeletal muscle via transcriptional repression of
CC       genes controlling lipid and amino acid metabolism in the muscle (By
CC       similarity). {ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- SUBUNIT: Binds DNA as a monomer or a homodimer (By similarity).
CC       Interacts with C1D, SP1 and ZNHIT1 (By similarity). Interacts with
CC       OPHN1 (via C-terminus) (By similarity). Interacts with PER2; the
CC       interaction associates PER2 to ARNTL promoter region (By similarity).
CC       Interacts with CRY1 (By similarity). Interacts with CCAR2 (By
CC       similarity). Interacts with NR2E3 (PubMed:15190009). Interacts with
CC       SIAH2 (By similarity). Interacts with FBXW7 and CDK1 (By similarity).
CC       Interacts with HUWE1 (By similarity). Interacts with NR0B2 (By
CC       similarity). Interacts with NFIL3 (By similarity). Interacts (via
CC       domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).
CC       {ECO:0000250|UniProtKB:P20393, ECO:0000250|UniProtKB:Q3UV55,
CC       ECO:0000269|PubMed:15190009}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC       Cytoplasm {ECO:0000250|UniProtKB:Q3UV55}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:Q3UV55}. Cell projection, dendritic spine
CC       {ECO:0000250|UniProtKB:Q3UV55}. Note=Localizes to the cytoplasm,
CC       dendrites and dendritic spine in the presence of OPHN1. Localizes
CC       predominantly to the nucleus at ZT8 whereas it is cytoplasmic at ZT20.
CC       Phosphorylation by CSNK1E enhances its cytoplasmic localization.
CC       {ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues and cell lines examined.
CC       Expressed at high levels in some squamous carcinoma cell lines.
CC   -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC       DNA-binding domain and a C-terminal ligand-binding domain.
CC   -!- PTM: Ubiquitinated, leading to its proteasomal degradation (By
CC       similarity). Ubiquitinated by the SCF(FBXW7) complex when
CC       phosphorylated by CDK1 leading to its proteasomal degradation (By
CC       similarity). Ubiquitinated by SIAH2; leading to its proteasomal
CC       degradation (By similarity). Rapidly ubiquitinated in response to
CC       inflammatory triggers and sumoylation is a prerequisite to its
CC       ubiquitination (By similarity). {ECO:0000250|UniProtKB:P20393,
CC       ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- PTM: Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a
CC       prerequisite to its ubiquitination. {ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic
CC       localization. {ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- PTM: Undergoes lysosome-mediated degradation in a time-dependent manner
CC       in the liver. {ECO:0000250|UniProtKB:Q3UV55}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
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; BC123488; AAI23489.1; -; mRNA.
DR   RefSeq; NP_001071568.1; NM_001078100.2.
DR   AlphaFoldDB; Q08E02; -.
DR   SMR; Q08E02; -.
DR   STRING; 9913.ENSBTAP00000016154; -.
DR   PaxDb; Q08E02; -.
DR   Ensembl; ENSBTAT00000016154; ENSBTAP00000016154; ENSBTAG00000012178.
DR   GeneID; 768225; -.
DR   KEGG; bta:768225; -.
DR   CTD; 9572; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012178; -.
DR   VGNC; VGNC:32228; NR1D1.
DR   eggNOG; KOG4846; Eukaryota.
DR   GeneTree; ENSGT00940000160548; -.
DR   HOGENOM; CLU_007368_2_4_1; -.
DR   InParanoid; Q08E02; -.
DR   OMA; LCPTHMY; -.
DR   OrthoDB; 1240230at2759; -.
DR   TreeFam; TF328382; -.
DR   Proteomes; UP000009136; Chromosome 19.
DR   Bgee; ENSBTAG00000012178; Expressed in retina and 104 other tissues.
DR   ExpressionAtlas; Q08E02; baseline and differential.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR   GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0001222; F:transcription corepressor binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR   GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0060086; P:circadian temperature homeostasis; ISS:UniProtKB.
DR   GO; GO:0005978; P:glycogen biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0061889; P:negative regulation of astrocyte activation; ISS:UniProtKB.
DR   GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR   GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:UniProtKB.
DR   GO; GO:0150079; P:negative regulation of neuroinflammatory response; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0070859; P:positive regulation of bile acid biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR   GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0042749; P:regulation of circadian sleep/wake cycle; ISS:UniProtKB.
DR   GO; GO:0045598; P:regulation of fat cell differentiation; ISS:UniProtKB.
DR   GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR   GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; ISS:UniProtKB.
DR   GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
DR   Gene3D; 1.10.565.10; -; 1.
DR   Gene3D; 3.30.50.10; -; 1.
DR   InterPro; IPR035500; NHR-like_dom_sf.
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   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF00105; zf-C4; 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   Acetylation; Activator; Biological rhythms; Cell projection; Cytoplasm;
KW   Differentiation; DNA-binding; Heme; Iron; Metal-binding; Nucleus;
KW   Phosphoprotein; Receptor; Reference proteome; Repressor; Synapse;
KW   Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..613
FT                   /note="Nuclear receptor subfamily 1 group D member 1"
FT                   /id="PRO_0000387612"
FT   DOMAIN          285..613
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        130..206
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         133..153
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         170..194
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..129
FT                   /note="Modulating"
FT   REGION          1..102
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1..70
FT                   /note="Required for phosphorylation by CSNK1E and
FT                   cytoplasmic localization"
FT                   /evidence="ECO:0000250|UniProtKB:Q3UV55"
FT   REGION          49..285
FT                   /note="Crucial for activation of GJA1"
FT                   /evidence="ECO:0000250"
FT   REGION          233..286
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..68
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        76..100
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        241..264
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         417
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250"
FT   BINDING         601
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         55
FT                   /note="Phosphoserine; by GSK3-beta"
FT                   /evidence="ECO:0000250|UniProtKB:P20393"
FT   MOD_RES         59
FT                   /note="Phosphoserine; by GSK3-beta"
FT                   /evidence="ECO:0000250|UniProtKB:P20393"
FT   MOD_RES         192
FT                   /note="N6-acetyllysine; by KAT5"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         193
FT                   /note="N6-acetyllysine; by KAT5"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         275
FT                   /note="Phosphothreonine; by CDK1"
FT                   /evidence="ECO:0000250|UniProtKB:Q3UV55"
FT   MOD_RES         590
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P20393"
SQ   SEQUENCE   613 AA;  66785 MW;  F03DCE683424438C CRC64;
     MTTLDSNNNT GGVITYIGSS GSSPNRTSPE SLYSDSSNGS FQSLTQGCPT YFPPSPTGSL
     TQDPARSFGS IPPSLGDDGS PSSSSSSSSS SSSSFYNGSP PGGLQVALED SNRVSPSKST
     SNITKLNGMV LLCKVCGDVA SGFHYGVHAC EGCKGFFRRS IQQNIQYKRC LKNENCSIVR
     INRNRCQQCR FKKCLSVGMS RDAVRFGRIP KREKQRMLAE MQSAMNLANN QLSSQCPLET
     PPTQHPTPGP MGPSPPPAPA PSPLVGFSQF PQQLTPPRSP SPEPTVEDVI SQVARAHREI
     FTYAHDKLGT SPGNFNANHA SGNRPATTPH RWESQGCPPA NDNIMAAQRH NEALNSLRQA
     SSSYPPPWPP GAAHHSCHQP NSNGHRLCPT HVYPAPEGEA PVNSPRQGNS KNILLACPMN
     MYPHGRSGRT VQEIWEDFSM SFTPAVREVV EFAKHIPGFR DLSQHDQVTL LKAGTFEVLM
     VRFASLFNVK DQTVMFLSRT TYSLQELGAM GMGDLLNAMF DFSEKLNSLA LTEEELGLFT
     AVVLVSADRS GMENSASVEQ LQETLLRALR ALVLKNRPSE TSRFTKLLLK LPDLRTLNNM
     HSEKLLSFRV DAQ
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024