Summary: Sterol-sensing domain of SREBP cleavage-activation
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Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that promote lipid synthesis in animal cells. They are embedded in the membranes of the endoplasmic reticulum (ER) in a helical hairpin orientation and are released from the ER by a two-step proteolytic process. Proteolysis begins when the SREBPs are cleaved at Site-1, which is located at a leucine residue in the middle of the hydrophobic loop in the lumen of the ER . Upon proteolytic processing SREBP can activate the expression of genes involved in cholesterol biosynthesis and uptake. SCAP stimulates cleavage of SREBPs via fusion of the their two C-termini . This domain is the transmembrane region that traverses the membrane eight times and is the sterol-sensing domain of the cleavage protein . WD40 domains are found towards the C-terminus.
Sakai J, Nohturfft A, Goldstein JL, Brown MS;, J Biol Chem. 1998;273:5785-5793.: Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies. PUBMED:9488713 EPMC:9488713
Colgan SM, Tang D, Werstuck GH, Austin RC;, Int J Biochem Cell Biol. 2007;39:1843-1851.: Endoplasmic reticulum stress causes the activation of sterol regulatory element binding protein-2. PUBMED:17604677 EPMC:17604677
Sakai J, Nohturfft A, Cheng D, Ho YK, Brown MS, Goldstein JL;, J Biol Chem. 1997;272:20213-20221.: Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein. PUBMED:9242699 EPMC:9242699
Yabe D, Xia ZP, Adams CM, Rawson RB;, Proc Natl Acad Sci U S A. 2002;99:16672-16677.: Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. PUBMED:12482938 EPMC:12482938
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Different members of the RND superfamily have been shown to transport hydrophobic drugs, fatty acids, bile salts, organic solvents, heavy metals, autoinducers and lipooligosaccharides in bacteria .
The clan contains the following 6 members:ACR_tran GerA MMPL Patched SecD_SecF Sterol-sensing
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Curation and family details
|Seed source:||Wood V|
|Author:||Wood V, Coggill P|
|Number in seed:||34|
|Number in full:||952|
|Average length of the domain:||148.90 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||14.06 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||3|
|Download:||download the raw HMM for this family|
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