Insig1
Encyclopedia
INSIG1 is short for insulin
-induced gene
1; it is located on chromosome
7 (7q36). This human gene encodes for a 277 AA long transmembrane protein with probably 6 transmembrane domains. It is localized in the ER
and seems to be expressed in all tissues, especially in liver
.
Both functions require the binding of INSIG1 protein via the same site.
There are two other proteins whose sterol-binding sites show a great similarity to the ones of SCAP and HMG-CoA-reductase and who might thus be regulated by INSIG1 as well:
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-induced gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
1; it is located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
7 (7q36). This human gene encodes for a 277 AA long transmembrane protein with probably 6 transmembrane domains. It is localized in the ER
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
and seems to be expressed in all tissues, especially in liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
.
Function
- INSIG1 plays an important role in the SREBPSterol regulatory element binding proteinSterol Regulatory Element-Binding Proteins are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors...
-mediated regulation of cholesterolCholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
biosynthesis: by binding to the sterol-sensing domain of SCAPSCAPSCAP may refer to:* Société de Constructions Automobiles* Security Content Automation Protocol* Separation of Content and Presentation* Shackled City Adventure Path* SREBP cleavage activating protein...
(SREBP cleavage activating protein) it makes the SCAP/SREBP complex stay longer in the ER, thus prohibiting SCAP from carrying activated SREBP to the golgi complex. This ultimately blocks SREBP from acting as a transcription factor for the SRE in the promotor region of the HMG-CoA-reductase gene and results in a decreased expression of HMG-CoA-reductase. - INSIG1 also binds to the sterol-sensing domain of HMG-Co-A-reductase, resulting in the enzyme's increased degradation.
Both functions require the binding of INSIG1 protein via the same site.
There are two other proteins whose sterol-binding sites show a great similarity to the ones of SCAP and HMG-CoA-reductase and who might thus be regulated by INSIG1 as well:
- Niemann-Pick disease C1 protein, which participates in the intracellular movement of cholesterol
- Patched, the receptor for Hedgehog, a protein that contains covalently bound cholesterol