XBP1_RAT
ID XBP1_RAT Reviewed; 267 AA.
AC Q9R1S4;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=X-box-binding protein 1 {ECO:0000250|UniProtKB:P17861};
DE AltName: Full=Hepatocarcinogenesis-related transcription factor;
DE Short=HTF;
DE Contains:
DE RecName: Full=X-box-binding protein 1, cytoplasmic form {ECO:0000250|UniProtKB:P17861};
DE Contains:
DE RecName: Full=X-box-binding protein 1, luminal form {ECO:0000250|UniProtKB:P17861};
GN Name=Xbp1 {ECO:0000250|UniProtKB:P17861, ECO:0000312|RGD:1303073};
GN Synonyms=Htf;
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 [GENOMIC DNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=Wistar;
RX PubMed=10675042; DOI=10.1016/s0378-1119(99)00479-5;
RA Kokura K., Kishimoto T., Tamura T.;
RT "Identity between rat htf and human xbp-1 genes: determination of gene
RT structure, target sequence, and transcription promotion function for HTF.";
RL Gene 241:297-307(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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).
CC -!- FUNCTION: Functions as a transcription factor during endoplasmic
CC reticulum (ER) stress by regulating the unfolded protein response
CC (UPR). Required for cardiac myogenesis and hepatogenesis during
CC embryonic development, and the development of secretory tissues such as
CC exocrine pancreas and salivary gland. Involved in terminal
CC differentiation of B lymphocytes to plasma cells and production of
CC immunoglobulins. Modulates the cellular response to ER stress in a
CC PIK3R-dependent manner. Binds to the cis-acting X box present in the
CC promoter regions of major histocompatibility complex class II genes.
CC Involved in VEGF-induced endothelial cell (EC) proliferation and
CC retinal blood vessel formation during embryonic development but also
CC for angiogenesis in adult tissues under ischemic conditions. Functions
CC also as a major regulator of the UPR in obesity-induced insulin
CC resistance and type 2 diabetes for the management of obesity and
CC diabetes prevention. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- FUNCTION: [Isoform 1]: Acts as a weak transcriptional factor. Together
CC with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1
CC transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent
CC signaling pathway leading to EC survival under disturbed flow/oxidative
CC stress. Binds to the ER stress response element (ERSE) upon ER stress.
CC Binds to the consensus 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to
CC cAMP responsive element (CRE)-like sequences. Associates preferentially
CC to the HDAC3 gene promoter region in a static flow-dependent manner.
CC Binds to the CDH5/VE-cadherin gene promoter region.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SUBUNIT: Isoform 1 interacts with HM13. Isoform 1 interacts with
CC RNF139; the interaction induces ubiquitination and degradation of
CC isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the
CC interaction obviates the need for ectodomain shedding prior HM13/SPP-
CC mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with HDAC3 and
CC AKT1; the interactions occur in endothelial cell (EC) under disturbed
CC flow. Isoform 1 interacts with the oncoprotein FOS. Interacts with
CC SIRT1. {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P17861}. Note=Colocalizes with ERN1 and KDR in
CC the endoplasmic reticulum in endothelial cells in a vascular
CC endothelial growth factor (VEGF)-dependent manner. Colocalizes in the
CC nucleus with SIRT1. {ECO:0000250|UniProtKB:P17861}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000250|UniProtKB:P17861}. Cytoplasm
CC {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17861}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Membrane
CC {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Note=Shows no preferential localization
CC to either the nucleus or the cytoplasm. Shuttles between the nucleus
CC and the cytoplasm in a CRM1-dependent manner. Localizes predominantly
CC at the endoplasmic reticulum membrane as a membrane-spanning protein;
CC whereas may be only marginally localized on the cytosolic side of the
CC ER membrane as a peripheral membrane. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=Additional isoforms seem to exist. {ECO:0000305};
CC Name=1;
CC IsoId=Q9R1S4-1; Sequence=Displayed;
CC -!- DOMAIN: Isoform 1 N-terminus domain is necessary for nuclear
CC localization targeting. Isoform 1 C-terminus domain confers
CC localization to the cytoplasm and is sufficient to impose rapid
CC degradation. Isoform 1 N-terminus and C-terminus regions are necessary
CC for DNA-binding and weak transcriptional activity, respectively.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: Isoform 1 is ubiquitinated, leading to proteasome-mediated
CC degradation in response to ER stress. {ECO:0000250|UniProtKB:O35426,
CC ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: X-box-binding protein 1, cytoplasmic form and luminal form are
CC produced by intramembrane proteolytic cleavage of ER membrane-anchored
CC isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and
CC VCP/p97-independent manner. X-box-binding protein 1, luminal form is
CC ubiquitinated leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:P17861}.
CC -!- PTM: Acetylated by EP300; acetylation positively regulates the
CC transcriptional activity of XBP1. Deacetylated by SIRT1; deacetylation
CC negatively regulates the transcriptional activity of XBP1.
CC {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; AB030238; BAA82600.1; -; Genomic_DNA.
DR EMBL; BC079450; AAH79450.1; -; mRNA.
DR PIR; JC4857; JC4857.
DR RefSeq; NP_001004210.1; NM_001004210.2. [Q9R1S4-1]
DR RefSeq; NP_001258660.1; NM_001271731.1.
DR AlphaFoldDB; Q9R1S4; -.
DR SMR; Q9R1S4; -.
DR STRING; 10116.ENSRNOP00000014044; -.
DR BindingDB; Q9R1S4; -.
DR ChEMBL; CHEMBL3632453; -.
DR PhosphoSitePlus; Q9R1S4; -.
DR PaxDb; Q9R1S4; -.
DR GeneID; 289754; -.
DR KEGG; rno:289754; -.
DR UCSC; RGD:1303073; rat. [Q9R1S4-1]
DR CTD; 7494; -.
DR RGD; 1303073; Xbp1.
DR eggNOG; KOG4005; Eukaryota.
DR HOGENOM; CLU_069050_0_0_1; -.
DR InParanoid; Q9R1S4; -.
DR OrthoDB; 1269901at2759; -.
DR PRO; PR:Q9R1S4; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q9R1S4; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA: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:0044389; F:ubiquitin-like protein ligase binding; ISO:RGD.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0071332; P:cellular response to fructose stimulus; ISO:RGD.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:0071353; P:cellular response to interleukin-4; ISS:UniProtKB.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0031670; P:cellular response to nutrient; ISO:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISS:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:RGD.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:RGD.
DR GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0002070; P:epithelial cell maturation; ISO:RGD.
DR GO; GO:0060691; P:epithelial cell maturation involved in salivary gland development; ISO:RGD.
DR GO; GO:0031017; P:exocrine pancreas development; ISO:RGD.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:RGD.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISO:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:1903489; P:positive regulation of lactation; ISS:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISS:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; ISS:UniProtKB.
DR GO; GO:0035470; P:positive regulation of vascular wound healing; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IDA:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0060096; P:serotonin secretion, neurotransmission; IDA:RGD.
DR GO; GO:0055092; P:sterol homeostasis; ISS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR Pfam; PF07716; bZIP_2; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Alternative splicing; Angiogenesis; Apoptosis;
KW Cleavage on pair of basic residues; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Endoplasmic reticulum; Membrane; Myogenesis;
KW Nucleus; Phosphoprotein; Reference proteome; Signal-anchor;
KW Stress response; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..267
FT /note="X-box-binding protein 1"
FT /id="PRO_0000076545"
FT CHAIN 1..188
FT /note="X-box-binding protein 1, cytoplasmic form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000432571"
FT CHAIN 191..267
FT /note="X-box-binding protein 1, luminal form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000432572"
FT TOPO_DOM 1..180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 181..198
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:P17861, ECO:0000255"
FT TOPO_DOM 199..267
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 63..126
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 35..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..87
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 69..85
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT REGION 91..126
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT SITE 185..186
FT /note="Cleavage; by HM13/SPP"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17861"
SQ SEQUENCE 267 AA; 29665 MW; B5A58F1D3FAA10B4 CRC64;
MVVVAAAPSA ASAAPKVLLL SGQPASGGRA LPLMVPGPRA AGSEASGTPQ ARKRQRLTHL
SPEEKALRRK LKNRVAAQTA RDRKKARMSE LEQQVVDLEE ENQKLQLENQ LLREKTHGLV
IENQELRTRL GMNALVTEEV SEAESKGNGV RLVAGSAESA ALRLRAPLQQ VQAQLSPPQN
IFPWILTLLP LQILSLISFW AFWTSWTLSC FSNVLPQSLL IWRNSQRSTQ KDLVPYQPPF
LCQWGPHQPS WKPLMNSFVL TMYTPSL
