LMPD Database

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LMP001471

UniProt Annotations

Entry Information
Gene NameSREBF chaperone
Protein EntrySCAP_HUMAN
UniProt IDQ12770
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q12770-1; Sequence=Displayed; Name=2; IsoId=Q12770-2; Sequence=VSP_007451, VSP_021106; Note=No experimental confirmation available.; Name=3; IsoId=Q12770-3; Sequence=VSP_007452; Note=No experimental confirmation available.; Name=4; IsoId=Q12770-4; Sequence=VSP_021105, VSP_021106; Note=No experimental confirmation available.;
DomainCholesterol 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 the ER membrane.
FunctionEscort protein required for cholesterol as well as lipid homeostasis. 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 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 SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).
InductionBy androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP).
Sequence CautionSequence=BAA12111.2; Type=Erroneous initiation; Evidence= ; Sequence=BAC11673.1; Type=Erroneous initiation; Evidence= ;
SimilarityBelongs to the WD repeat SCAP family.
SimilarityContains 1 SSD (sterol-sensing) domain.
SimilarityContains 7 WD repeats. {ECO
Subcellular LocationEndoplasmic reticulum membrane {ECO
SubunitMembrane region forms a homotetramer. Forms a stable complex with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal 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 SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 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.