Protein: X-box-binding protein 1 (XBP-1) (Tax-responsive element-binding protein 5) (TREB-5) [Cleaved into: X-box-binding protein 1, cytoplasmic form; X-box-binding protein 1, luminal form] (P17861)
Organism: Homo sapiens (Human)
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 (By similarity). 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 (By similarity).
Subcellular location: Endoplasmic reticulum {ECO:0000269|PubMed:23529610}. Note=Colocalizes with ERN1 and KDR in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner (PubMed:23529610). {ECO:0000269|PubMed:23529610}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296}. Cytoplasm {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:25190803}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:25239945}; Single-pass type II membrane protein {ECO:0000269|PubMed:25239945}. Endoplasmic reticulum membrane {ECO:0000303|PubMed:25239945}; Peripheral membrane protein {ECO:0000303|PubMed:25239945}. Membrane {ECO:0000269|PubMed:19394296}; Peripheral membrane protein {ECO:0000303|PubMed:19394296}. Note=Shows no preferential localization to either the nucleus or the cytoplasm (By similarity). Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner (PubMed:16461360). 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 (PubMed:19394296, PubMed:25190803). {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:25190803}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:20955178}. Cytoplasm {ECO:0000250|UniProtKB:O35426}. Note=Localizes predominantly in the nucleus. Colocalizes in the nucleus with SIRT1. Translocates into the nucleus in a PIK3R-, ER stress-induced- and/or insulin-dependent manner (By similarity). {ECO:0000250|UniProtKB:O35426}.; SUBCELLULAR LOCATION: [X-box-binding protein 1, cytoplasmic form]: Cytoplasm {ECO:0000269|PubMed:25239945}. Nucleus {ECO:0000269|PubMed:25239945}. Note=Localizes in the cytoplasm and nucleus after HM13/SPP-mediated intramembranaire proteolytic cleavage of isoform 1 (PubMed:25239945). {ECO:0000269|PubMed:25239945}.
Interaction partners:
- Cyclic AMP-dependent transcription factor ATF-6 alpha
- Serine/threonine-protein kinase/endoribonuclease IRE1
- DNA damage-inducible transcript 3 protein
- Hypoxia-inducible factor 1-alpha
- Endoplasmic reticulum chaperone BiP
- ER degradation-enhancing alpha-mannosidase-like protein 1
- DnaJ homolog subfamily B member 9
- DnaJ homolog subfamily C member 3
- Hypoxia up-regulated protein 1
- TATA-box-binding protein
Sequence:
MVVVAAAPNPADGTPKVLLLSGQPASAAGAPAGQALPLMVPAQRGASPEAASGGLPQARKRQRLTHLSPEEKALRRKLKNRVAAQTARDRKKARMSELEQQVVDLEEENQKLLLENQLLREKTHGLVVENQELRQRLGMDALVAEEEAEAKGNEVRPVAGSAESAALRLRAPLQQVQAQLSPLQNISPWILAVLTLQIQSLISCWAFWTTWTQSCSSNALPQSLPAWRSSQRSTQKDPVPYQPPFLCQWGRHQPSWKPLMN