SCAP
SCAP (SREBF chaperone, also known as KIAA0199) is an escort protein required for cholesterol and lipid homeostasis. It controls export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi apparatus, and so governs the processing of sterol regulatory element-binding proteins. Browse Assay Genie's current range of SCAP research reagents below, or read on for the biology behind the target.
SCAP is a membrane escort protein that links cellular sterol levels to lipid gene expression. When cholesterol is low, it regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi, thereby controlling the processing of the sterol regulatory element-binding proteins SREBF1/SREBP1 and SREBF2/SREBP2. At high sterol concentrations, SCAP forms a ternary complex with INSIG1 or INSIG2. This masks the ER export signal in SCAP and keeps the complex in the endoplasmic reticulum.
Low sterol concentrations release INSIG and cause a conformational change in the sterol-sensing domain (SSD) of SCAP, which binds cholesterol. The ER export signal is then unmasked, and the SCAP-SREBP complex is recruited into COPII-coated vesicles and carried to the Golgi. There the SREBPs are processed, releasing the transcription factor fragment from the membrane. This fragment enters the nucleus and up-regulates LDLR, INSIG1 and the mevalonate pathway. UniProt records SCAP at the endoplasmic reticulum membrane, the Golgi apparatus membrane and COPII-coated vesicle membranes, which matches its role as a shuttling escort.
The human SCAP gene encodes a protein with a sterol sensing domain and seven WD domains, and it belongs to the WD repeat SCAP family. HGNC places it in the WD repeat domain containing gene group and lists KIAA0199 as a previous symbol. Alternative splicing gives rise to multiple transcript variants. Mouse and rat each have a Scap ortholog. Researchers studying the SCAP protein often examine it alongside its partners SREBP1, SREBP2, INSIG1 and INSIG2 to dissect sterol-regulated signalling.
SCAP is required for cholesterol homeostasis and senses sterol levels through its SSD domain, making it a central subject in studies of cellular cholesterol control.
SCAP regulates ER-to-Golgi export of the SCAP-SREBP complex, which determines how SREBF1 and SREBF2 are processed to release their transcription factor fragments.
By controlling SREBP activation, SCAP influences up-regulation of LDLR, INSIG1 and the mevalonate pathway, linking sterol status to lipid gene expression.
Unmasking of the SCAP ER export signal drives recruitment into COPII-coated vesicles, offering a model for studying regulated protein export from the endoplasmic reticulum.
SCAP is an escort protein that moves SREBP transcription factors from the endoplasmic reticulum to the Golgi when sterol levels are low. In the Golgi, SREBPs are processed and their active fragments enter the nucleus to up-regulate LDLR, INSIG1 and the mevalonate pathway.
SCAP stands for SREBF chaperone, and UniProt names the protein sterol regulatory element-binding protein cleavage-activating protein. KIAA0199 is a previous gene symbol. The gene produces multiple transcript variants through alternative splicing, according to the NCBI Gene summary.
Yes. Mouse and rat both have a Scap ortholog, so the sterol-sensing escort mechanism can be studied in common rodent models. Cross-reactivity differs between reagents, so check the datasheet of any product for its validated reactivity.
SREBP transcription factors, INSIG retention partners and downstream sterol-responsive targets linked to SCAP signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q12770; product specifications from Assay Genie datasheets.