Protein also known as:
Cyclic AMP-responsive element-binding protein 4 (CREB-4).
Cleaved into:
Processed cyclic AMP-responsive element-binding protein 3-like protein 4.
Transcriptional activator that may play a role in the unfolded protein response. Binds to the UPR element (UPRE) but not to CRE element. Preferentially binds DNA with to the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional activation activity from UPRE. Binds to NF-kappa-B site and has transcriptional activation activity from NF-kappa-B-containing regulatory elements (By similarity).
Regulated intramembrane proteolysis of the factors SREBP and ATF6 represents a central control mechanism in sterol homeostasis and stress response within the endoplasmic reticulum. Here, we compare localization of ATF6-related bZip factors CREB4, CREB-H, Luman, and OASIS. These factors contain the defining features of a bZip domain, a predicted transmembrane domain and an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites. Each factor localizes to the endoplasmic reticulum (ER), but a population of CREB4 was also observed in the Golgi. Deletion of the transmembrane domain in CREB4 resulted in efficient nuclear accumulation. An N-terminal variant of CREB4 containing the BZIp domain potently activated expression from a target gene containing ATF6 binding sites and from the promoter for the ER chaperone GRP78/BIP. CREB4 was cleaved in a site-specific manner in response to brefeldin A disruption of the Golgi or by coexpression with S1P but only after deletion or substitution of its C-terminal lumenal domain. Thus, S1P cleavage of CREB4 may be suppressed by a determinant in the C-terminal region. Dithiothreitol induced more complete transport of CREB4 to the Golgi, but not cleavage. Together, the data identify at least one additional bZip factor whose localization responds to ER stress, and we propose a model based on these results that indicates additional levels of control of this novel class of transcription factors.
Interacting selectively and non-covalently with DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
IEAInterPro 2 GO
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]‹silver
Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription. The transcription factor may or may not also interact selectively with a protein or macromolecular complex.
IEAInterPro 2 GO
GO biological process
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]‹silver
Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an unfolded protein stimulus.
Protein involved in the transfer of genetic information from DNA to messenger RNA (mRNA) by DNA-directed RNA polymerase. In the case of some RNA viruses, protein involved in the transfer of genetic information from RNA to messenger RNA (mRNA) by RNA-directed RNA polymerase.
Protein involved in the unfolded protein response. An accumulation of unfolded proteins in the ER lumen triggers a stress response, resulting in the transcriptional induction in the nucleus of a set of genes, whose products are involved in protein folding, assembly and modification as well as in phospholipid biosynthesis. The unfolded protein response (UPR) is the intracellular pathway that mediates signaling from the endoplasmic reticulum (ER) to the nucleus. UPR is also tightly linked to ER-associated protein degradation (ERAD). UPR is a ubiquitous mechanism observed in all eukaryotes from humans to yeast.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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