ID:SRBP2_HUMAN DESCRIPTION: RecName: Full=Sterol regulatory element-binding protein 2; Short=SREBP-2; AltName: Full=Class D basic helix-loop-helix protein 2; Short=bHLHd2; AltName: Full=Sterol regulatory element-binding transcription factor 2; Contains: RecName: Full=Processed sterol regulatory element-binding protein 2; FUNCTION: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes. SUBUNIT: Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA. Component of SCAP/SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts (via C-terminus domain) with RNF139. INTERACTION: P84022:SMAD3; NbExp=3; IntAct=EBI-465059, EBI-347161; P08047:SP1; NbExp=3; IntAct=EBI-465059, EBI-298336; P04637:TP53; NbExp=3; IntAct=EBI-465059, EBI-366083; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle, COPII-coated vesicle membrane; Multi-pass membrane protein. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols. SUBCELLULAR LOCATION: Processed sterol regulatory element-binding protein 2: Nucleus. TISSUE SPECIFICITY: Ubiquitously expressed in adult and fetal tissues. PTM: At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. PTM: Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression (By similarity). SIMILARITY: Belongs to the SREBP family. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SEQUENCE CAUTION: Sequence=AAH51799.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q12772
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008022 protein C-terminus binding GO:0044212 transcription regulatory region DNA binding GO:0046983 protein dimerization activity GO:0070888 E-box binding GO:0000247 C-8 sterol isomerase activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006629 lipid metabolic process GO:0008202 steroid metabolic process GO:0008203 cholesterol metabolic process GO:0009267 cellular response to starvation GO:0010886 positive regulation of cholesterol storage GO:0042632 cholesterol homeostasis GO:0045540 regulation of cholesterol biosynthetic process GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0071404 cellular response to low-density lipoprotein particle stimulus GO:0071499 cellular response to laminar fluid shear stress GO:0072368 regulation of lipid transport by negative regulation of transcription from RNA polymerase II promoter GO:0090370 negative regulation of cholesterol efflux GO:1903146 regulation of mitophagy GO:1903955 positive regulation of protein targeting to mitochondrion
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
