Human Gene SCAP (uc003crh.1) Description and Page Index
Description: Homo sapiens SREBF chaperone (SCAP), mRNA. RefSeq Summary (NM_012235): This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]. Transcript (Including UTRs) Position: hg19 chr3:47,455,184-47,517,445 Size: 62,262 Total Exon Count: 23 Strand: - Coding Region Position: hg19 chr3:47,455,344-47,484,483 Size: 29,140 Coding Exon Count: 22
ID:SCAP_HUMAN DESCRIPTION: RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein; Short=SCAP; Short=SREBP cleavage-activating protein; FUNCTION: Escort 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). SUBUNIT: Membrane 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. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Golgi apparatus membrane; Multi- pass membrane protein (By similarity). Cytoplasmic vesicle, COPII- coated vesicle membrane; Multi-pass membrane protein (By similarity). Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols (By similarity). INDUCTION: By androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP). DOMAIN: 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 the ER membrane (By similarity). SIMILARITY: Belongs to the WD repeat SCAP family. SIMILARITY: Contains 1 SSD (sterol-sensing) domain. SIMILARITY: Contains 7 WD repeats. SEQUENCE CAUTION: Sequence=BAA12111.2; Type=Erroneous initiation; Sequence=BAC11673.1; Type=Erroneous initiation;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): SCAP CDC HuGE Published Literature: SCAP
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q12770
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.