Protein: X-box-binding protein 1 (Hepatocarcinogenesis-related transcription factor) (HTF) [Cleaved into: X-box-binding protein 1, cytoplasmic form; X-box-binding protein 1, luminal form] (Q9R1S4)
Organism: Rattus norvegicus (Rat)
Function: Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland. Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes. Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions. Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P17861}. Note=Colocalizes with ERN1 and KDR in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner. Colocalizes in the nucleus with SIRT1. {ECO:0000250|UniProtKB:P17861}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000250|UniProtKB:P17861}. Cytoplasm {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17861}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:P17861}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein {ECO:0000250|UniProtKB:P17861}. Membrane {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein {ECO:0000250|UniProtKB:P17861}. Note=Shows no preferential localization to either the nucleus or the cytoplasm. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Localizes predominantly at the endoplasmic reticulum membrane as a membrane-spanning protein; whereas may be only marginally localized on the cytosolic side of the ER membrane as a peripheral membrane. {ECO:0000250|UniProtKB:O35426, ECO:0000250|UniProtKB:P17861}.
Sequence: MVVVAAAPSAASAAPKVLLLSGQPASGGRALPLMVPGPRAAGSEASGTPQARKRQRLTHLSPEEKALRRKLKNRVAAQTARDRKKARMSELEQQVVDLEEENQKLQLENQLLREKTHGLVIENQELRTRLGMNALVTEEVSEAESKGNGVRLVAGSAESAALRLRAPLQQVQAQLSPPQNIFPWILTLLPLQILSLISFWAFWTSWTLSCFSNVLPQSLLIWRNSQRSTQKDLVPYQPPFLCQWGPHQPSWKPLMNSFVLTMYTPSL
InterPro domains: - IPR052470: Endoplasmic Reticulum Stress-Regulated Transcription Factor (family) [8-256]
- IPR004827: Basic-leucine zipper domain (domain) [61-126]
- IPR046347: Basic-leucine zipper domain superfamily (homologous_superfamily) [66-123]
Interaction partners: - DNA damage-inducible transcript 3 protein
- Serine/threonine-protein kinase/endoribonuclease IRE1
- Cyclic AMP-dependent transcription factor ATF-6 alpha
- Cyclic AMP-dependent transcription factor ATF-4
- Endoplasmic reticulum chaperone BiP
- TATA box binding protein
- Hypoxia-inducible factor 1-alpha
- TATA-box binding protein like 1
- TATA box-binding protein-like 2
- Endoplasmin
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:0097159 (organic cyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:1901363 (heterocyclic compound binding), GO:0003676 (nucleic acid binding), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0003677 (DNA binding), GO:0043565 (sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0048522 (positive regulation of cellular process), GO:0009607 (response to biotic stimulus), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0043207 (response to external biotic stimulus), GO:0060548 (negative regulation of cell death), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0006979 (response to oxidative stress), GO:0009410 (response to xenobiotic stimulus), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0009891 (positive regulation of biosynthetic process), GO:0009991 (response to extracellular stimulus), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:1901698 (response to nitrogen compound), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0009617 (response to bacterium), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0034599 (cellular response to oxidative stress), GO:0071417 (cellular response to organonitrogen compound), GO:1901652 (response to peptide), GO:0034097 (response to cytokine), GO:0097305 (response to alcohol), GO:0032496 (response to lipopolysaccharide), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0043069 (negative regulation of programmed cell death), GO:0071310 (cellular response to organic substance), GO:0043067 (regulation of programmed cell death), GO:0062197 (cellular response to chemical stress), GO:1901699 (cellular response to nitrogen compound), GO:0002237 (response to molecule of bacterial origin), GO:0010468 (regulation of gene expression), GO:0043434 (response to peptide hormone), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0032870 (cellular response to hormone stimulus), GO:0010243 (response to organonitrogen compound), GO:0033993 (response to lipid), GO:0031667 (response to nutrient levels), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0014070 (response to organic cyclic compound), GO:0051252 (regulation of RNA metabolic process), GO:1901701 (cellular response to oxygen-containing compound), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0042981 (regulation of apoptotic process), GO:0071375 (cellular response to peptide hormone stimulus), GO:0032868 (response to insulin), GO:0071392 (cellular response to estradiol stimulus), GO:0043066 (negative regulation of apoptotic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0071407 (cellular response to organic cyclic compound), GO:0071345 (cellular response to cytokine stimulus), GO:0071396 (cellular response to lipid), GO:1901653 (cellular response to peptide), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:0032869 (cellular response to insulin stimulus), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)