background:
SCAP is an escort protein required for cholestrol and lipid homeostasis. Cholesterol homeostasis in animal cells is achieved by regulated cleavage of SREBPs, membrane-bound transcription factors. SCAP forms a complex with SREBPs in order to release the active domains of SREBPs.
Function:
Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SRESF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SRESF in the Golgi, release of the transcription factor fragment of SRESF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).
Subunit:
Membrane region forms a homotetramer. Forms a stable complex with SRESF1/SREBP1 or SRESF2/SREBP2 through its SLCterminal cytoplasmic domain. Forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations. Interacts with the SEC23/SEC24 complex in a SAR1-GTP-dependent manner through an ER export signal in its third cytoplasmic loop. Binds cholesterol through its SSC domain (By similarity). Component of SCAP/SREBP complex composed of SRESF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SRESF2 proteolytic processing. Interacts with RNF139; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP/SREBP complex.
Subcellular Location:
Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle, COPII-coated vesicle membrane; Multi-pass membrane protein.
Similarity:
Belongs to the WD repeat SCAP family.
Contains 1 SSD (sterol-sensing) domain.
Contains 7 WD repeats.
Database links:
UniProtKB/Swiss-Prot: Q12770.4
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
|
|
