SREBP cleavage-activating protein

Sterol regulatory element-binding protein cleavage-activating protein, also known as SREBP cleavage-activating protein or SCAP, is a protein that in humans is encoded by the SCAP gene.^[5][6][7][8]

SCAP
Identifiers
Aliases	SCAP, entrez:22937, SREBF chaperone
External IDs	OMIM: 601510; MGI: 2135958; HomoloGene: 8160; GeneCards: SCAP; OMA:SCAP - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 47,413,681 bp[1] End 47,477,126 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F2|9 59.91 cM Start 110,162,356 bp[2] End 110,214,018 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal cortex mucosa of transverse colon right lobe of liver skin of abdomen skin of leg right hemisphere of cerebellum right ovary left ovary right testis Top expressed in retinal pigment epithelium secondary oocyte otic vesicle primary oocyte zygote saccule transitional epithelium of urinary bladder epithelium of stomach otic placode left lobe of liver More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding cholesterol binding unfolded protein binding protein-containing complex binding sterol binding Cellular component endoplasmic reticulum membrane ER to Golgi transport vesicle membrane integral component of membrane Golgi apparatus membrane intracellular membrane-bounded organelle Golgi membrane endoplasmic reticulum cytoplasmic vesicle protein-containing complex Biological process response to hypoxia ageing cholesterol metabolic process response to insulin regulation of fatty acid biosynthetic process negative regulation of cholesterol biosynthetic process steroid metabolic process lipid metabolism regulation of fatty acid metabolic process SREBP signaling pathway regulation of cholesterol biosynthetic process immune response cellular lipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 22937 235623 Ensembl ENSG00000114650 ENSMUSG00000032485 UniProt Q12770 Q6GQT6 RefSeq (mRNA) NM_012235 NM_001320044 NM_001001144 NM_001103162 RefSeq (protein) NP_001306973 NP_036367 NP_001001144 NP_001096632 Location (UCSC) Chr 3: 47.41 – 47.48 Mb Chr 9: 110.16 – 110.21 Mb PubMed search [3] [4]
Wikidata
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SCAP contains a sterol-sensing domain (SSD) and seven WD domains. In cholesterol-depleted cells, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi apparatus. The SREBPs are then proteolytically cleaved and stimulate sterol biosynthesis.^[5]

Function

SCAP is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP). SCAP is an integral membrane protein located in the endoplasmic reticulum (ER). One of the cytosolic regions of SCAP contains a hexapeptide amino acid sequence, MELADL, that functions to detect cellular cholesterol. When cholesterol is present, SCAP undergoes a conformational change that prevents it from activating SREBP and cholesterol synthesis does not occur.^[9]

Structure

Scap has 8 transmembrane domains and both the N-terminal and C-terminal face the cytoplasm. Also, it binds SREBP by a series of consecutive WD repeats on its C-terminus.^[10]