sterol regulatory element-binding protein cleavage-activating protein; SREBP cleavage-activating protein; SCAP (SCAP, KIAA0199, PSEC0227)

Function

• escort protein required for cholesterol as well as lipid homeostasis
• functions to retain SREBPs in the endoplasmic reticulum in the presence of sterols & escort them to the GOLGI in the absence of sterols; this presumably allows close monitoring & response to fluctuations in membrane bilayer sterols
• regulates export of the SCAP/SREBF 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 & retention of the complex in the ER
• low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus & up-regulation of LDLR, INSIG1 & the mevalonate pathway (putative)
• forms a stable complex with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal cytoplasmic domain for ER anchoring
• forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations
• interacts with the SEC23/SEC24 complex (SAR1-GTP-dependent) through an ER export signal in its 3rd cytoplasmic loop
• binds cholesterol through its SSC domain (putative)

Structure

• membrane region forms a homotetramer
• cholesterol bound to SSC domain of SCAP or oxysterol bound to INSIG1/2 leads to masking of an ER export signal on SCAP possibly by moving the signal further away from ER membrane
• belongs to the WD repeat SCAP family
• contains 1 SSD (sterol-sensing) domain
• contains 7 WD repeats

Compartment

• multi-pass membrane protein
• endoplasmic reticulum membrane
• Golgi membrane
• cytoplasmic vesicle, COPII- coated vesicle membrane
• moves from the endoplasmic reticulum to the Golgi in the absence of sterols (putative)

Alternative splicing

named isoforms=4

Expression

• induced by androgen-bound AR & glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP)

More general terms

• transmembrane 8 protein
• glycoprotein
• WD repeat protein family
• phosphoprotein

Additional terms

• sterol regulatory element binding protein (SREBP)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=22937
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:22937
• OMIM: https://mirror.omim.org/entry/601510
• UniProt: http://www.uniprot.org/uniprot/Q12770.html