This gene encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a decamer flanking the low density lipoprotein receptor gene and some genes involved in sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene.
FUNCTION: SwissProt: P36956 # Transcriptional activator that binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity, binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates the transcription of genes for sterol biosynthesis and the LDL receptor gene. SIZE: 1147 amino acids; 121645 Da SUBUNIT: Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols. TISSUE SPECIFICITY: Expressed in a wide variety of tissues, most abundant in liver and adrenal gland. In fetal tissues lung and liver shows highest expression. Isoform SREBP-1C predominates in liver, adrenal gland and ovary, whereas isoform SREBP-1A predominates in hepatoma cell lines. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, brain, white fat, and muscle. PTM: Under sterol-depleted conditions, SREBPs are cleaved sequentially by site-1 and site-2 protease. The first cleavage occurs within the luminal loop and is directly regulated by sterols. The second cleavage by site-2 protease occurs within the first transmembrane stretch and liberates the soluble transcription factor. Cleavage by the cysteine proteases, caspase- 3 and caspase-7, is induced during apoptosis, independent of sterol levels. SIMILARITY: SwissProt: P36956 ## Contains 1 basic helix-loop-helix (bHLH) domain. MISCELLANEOUS: SREBPs have to be in a complex with the cleavage- activating protein (SCAP) to move to the Golgi and be cleaved by site-1 protease.
Safety Information according to GHS
Product Usage Statements
Routinely evaluated by immunoblot.
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Storage and Shipping Information
Stable for 2 years at -20°C from date of shipment. Upon first thaw, and prior to removing the cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20°C. Avoid repeated freeze/thaw cycles, which may damage IgG and affect product performance. Note: Variability in freezer temperatures below -20°C may cause glycerol-containing solutions to become frozen during storage.
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