SREBP cleavage-activating protein: Difference between revisions

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'''SREBP cleavage-activating protein''' (SCAP) is a [[protein]] that in humans is encoded by the SCAP [[gene]]. SCAP is an [[enzyme]] that plays a crucial role in the regulation of [[lipid]] metabolism.
 
{{Infobox protein
| name = SREBP cleavage-activating protein
| image = <!-- Image removed -->
| caption = <!-- Caption removed -->
| symbol = SCAP
| altsymbols =
| hgncid = 10587
| omim = 601510
| entrezgene = 9991
| refseq = NM_012238
| uniprot = Q12770
| chromosomal_location = 3p21.31
}}
 
'''SREBP cleavage-activating protein''' ('''SCAP''') is a crucial component in the regulation of lipid homeostasis. It is involved in the [[SREBP]] (Sterol Regulatory Element-Binding Proteins) pathway, which controls the synthesis of [[cholesterol]] and [[fatty acids]] in the body.


== Function ==
== Function ==
SCAP is an essential component of the [[sterol]] regulatory element-binding protein (SREBP) pathway, which regulates the synthesis of [[cholesterol]] and [[fatty acids]] in the [[liver]]. SCAP binds to SREBPs and escorts them from the [[endoplasmic reticulum]] (ER) to the [[Golgi apparatus]], where the SREBPs are cleaved by [[site-1 protease]] (S1P) and [[site-2 protease]] (S2P). This cleavage releases the transcriptionally active N-terminal domain of the SREBPs, which then enters the [[nucleus]] and activates the transcription of genes involved in lipid synthesis and uptake.
SCAP is an integral membrane protein located in the [[endoplasmic reticulum]] (ER). It functions as a sterol sensor and is responsible for the transport of SREBPs from the ER to the [[Golgi apparatus]]. In the Golgi, SREBPs undergo two sequential proteolytic cleavages, which release the active form of SREBPs that can enter the [[nucleus]] and activate the transcription of genes involved in lipid biosynthesis.


== Structure ==
== Mechanism ==
SCAP is a polytopic [[transmembrane protein]] that contains a sterol-sensing domain (SSD). The SSD is responsible for sensing changes in cellular sterol levels and regulating the movement of SCAP and SREBP from the ER to the Golgi. When sterol levels are high, SCAP binds to [[insulin-induced gene]] (INSIG) proteins in the ER, preventing the transport of SCAP and SREBP to the Golgi and thereby inhibiting lipid synthesis.
Under conditions of low cellular cholesterol, SCAP escorts SREBPs to the Golgi apparatus. This process is facilitated by the interaction of SCAP with [[COPII]] vesicles, which mediate the transport of proteins from the ER to the Golgi. Once in the Golgi, SREBPs are cleaved by site-1 protease (S1P) and site-2 protease (S2P), releasing the N-terminal domain of SREBPs. This domain then translocates to the nucleus, where it binds to sterol regulatory elements (SREs) in the promoter regions of target genes, enhancing their transcription.


== Clinical significance ==
== Regulation ==
Mutations in the SCAP gene can lead to dysregulation of lipid metabolism, contributing to conditions such as [[familial hypercholesterolemia]] and [[metabolic syndrome]]. In addition, overexpression of SCAP has been associated with the progression of certain types of [[cancer]], including [[hepatocellular carcinoma]] and [[prostate cancer]].
The activity of SCAP is tightly regulated by the sterol content of the cell. When cholesterol levels are high, SCAP undergoes a conformational change that prevents its interaction with COPII vesicles, thereby retaining SREBPs in the ER and reducing the transcription of lipid biosynthetic genes. This feedback mechanism ensures that cholesterol synthesis is decreased when cellular cholesterol is sufficient.


[[File:SCAP protein structure.jpg|thumb|right|300px|Structure of the SCAP protein. The SSD is shown in red.]]
== Clinical Significance ==
Mutations in the SCAP gene can lead to dysregulation of lipid metabolism, contributing to conditions such as [[hypercholesterolemia]] and [[atherosclerosis]]. Understanding the role of SCAP in lipid homeostasis is crucial for developing therapeutic strategies for these metabolic disorders.


== See also ==
== See Also ==
* [[Sterol regulatory element-binding protein]]
* [[Cholesterol metabolism]]
* [[Lipid metabolism]]
* [[Lipid biosynthesis]]
* [[Cholesterol]]
* [[Endoplasmic reticulum]]
* [[Fatty acid]]
* [[Golgi apparatus]]


== References ==
== References ==
<references />
<references />
== External Links ==
* [SCAP at UniProt](https://www.uniprot.org/uniprot/Q12770)
* [SCAP Gene - GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SCAP)
{{Protein-stub}}


[[Category:Proteins]]
[[Category:Proteins]]
[[Category:Enzymes]]
[[Category:Metabolism]]
[[Category:Lipid metabolism]]
[[Category:Cholesterol]]
[[Category:Human genes]]
[[Category:Human proteins]]
{{protein-stub}}
{{medicine-stub}}

Latest revision as of 21:45, 29 December 2024


SREBP cleavage-activating protein (SCAP) is a crucial component in the regulation of lipid homeostasis. It is involved in the SREBP (Sterol Regulatory Element-Binding Proteins) pathway, which controls the synthesis of cholesterol and fatty acids in the body.

Function[edit]

SCAP is an integral membrane protein located in the endoplasmic reticulum (ER). It functions as a sterol sensor and is responsible for the transport of SREBPs from the ER to the Golgi apparatus. In the Golgi, SREBPs undergo two sequential proteolytic cleavages, which release the active form of SREBPs that can enter the nucleus and activate the transcription of genes involved in lipid biosynthesis.

Mechanism[edit]

Under conditions of low cellular cholesterol, SCAP escorts SREBPs to the Golgi apparatus. This process is facilitated by the interaction of SCAP with COPII vesicles, which mediate the transport of proteins from the ER to the Golgi. Once in the Golgi, SREBPs are cleaved by site-1 protease (S1P) and site-2 protease (S2P), releasing the N-terminal domain of SREBPs. This domain then translocates to the nucleus, where it binds to sterol regulatory elements (SREs) in the promoter regions of target genes, enhancing their transcription.

Regulation[edit]

The activity of SCAP is tightly regulated by the sterol content of the cell. When cholesterol levels are high, SCAP undergoes a conformational change that prevents its interaction with COPII vesicles, thereby retaining SREBPs in the ER and reducing the transcription of lipid biosynthetic genes. This feedback mechanism ensures that cholesterol synthesis is decreased when cellular cholesterol is sufficient.

Clinical Significance[edit]

Mutations in the SCAP gene can lead to dysregulation of lipid metabolism, contributing to conditions such as hypercholesterolemia and atherosclerosis. Understanding the role of SCAP in lipid homeostasis is crucial for developing therapeutic strategies for these metabolic disorders.

See Also[edit]

References[edit]

<references />

External Links[edit]


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