SCAP

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.

Full Name

SREBF Chaperone

Function

Escort protein required for cholesterol as well as lipid homeostasis (By similarity).
Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity).
At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (By similarity).
Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).
Binds cholesterol via its SSD domain (By similarity).

Biological Process

Biological Process agingIEA:Ensembl
Biological Process cellular lipid metabolic processIEA:Ensembl
Biological Process cholesterol metabolic processISS:UniProtKB
Biological Process COPII-coated vesicle cargo loadingISS:UniProtKB
Biological Process immune responseIEA:Ensembl
Biological Process negative regulation of cholesterol biosynthetic process1 PublicationNAS:UniProtKB
Biological Process positive regulation of cholesterol biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cholesterol biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of fatty acid biosynthetic processIEA:Ensembl
Biological Process response to hypoxiaIEA:Ensembl
Biological Process response to insulinIEA:Ensembl
Biological Process SREBP signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Endoplasmic reticulum membrane
Golgi apparatus membrane
Cytoplasmic vesicle, COPII-coated vesicle membrane
Moves from the endoplasmic reticulum to the Golgi in the absence of sterols (By similarity).
Requires the presence of SPRING1 for proper localization to endoplasmic reticulum (PubMed:32111832).

Topology

Cytoplasmic: 1-18
Helical: 19-39
Lumenal: 40-279
Helical: 280-300
Cytoplasmic: 301-312
Helical: 313-333
Lumenal: 334-344
Helical: 345-365
Cytoplasmic: 366-401
Helical: 402-422
Lumenal: 423
Helical: 424-444
Cytoplasmic: 445-518
Helical: 519-539
Lumenal: 540-709
Helical: 710-730
Cytoplasmic: 731-1279

PTM

Ubiquitinated at Lys-454 and Lys-466. RNF145 triggers ubiquitination of SCAP, likely inhibiting SCAP-SREBP complex transport to the Golgi apparatus and the subsequent processing/maturation of SREBF2/SREBP2.