SREBF2

GeneName

SREBF2

Summary

SREBF2, also known as SREBP-2, is a 124 kDa transcription factor that plays a central role in the regulation of cholesterol and lipid metabolism. It is primarily expressed in the liver and is localised to various cellular compartments including the endoplasmic reticulum, Golgi apparatus, and nucleus. SREBF2 functions by binding to specific DNA sequences in the promoter regions of target genes, regulating their transcription in response to cellular lipid levels. It is involved in the SREBP signaling pathway and has a significant role in cholesterol homeostasis, responding to stimuli such as low-density lipoprotein particles and starvation. Additionally, SREBF2 is implicated in the regulation of miRNA transcription and has been shown to influence processes such as mitophagy and Notch signalling.

Importance

SREBF2 is relevant to: - Cholesterol metabolism and homeostasis, making it a target for understanding dyslipidaemias and cardiovascular diseases - Lipid-related disorders, including obesity and metabolic syndrome, due to its role in lipid biosynthesis and storage - Neurodegenerative diseases, as it negatively regulates amyloid-beta clearance, potentially linking it to Alzheimer’s disease - Cancer biology, through its influence on cellular responses to nutrient availability and its regulatory effects on transcription

Top Products

For researchers investigating SREBF2, we highly recommend the well-cited polyclonal antibody, Anti-SREBP2 antibody (ab30682). This antibody has garnered 208 citations, reflecting its reliability and trust within the scientific community. It is particularly effective for Western blotting (WB) and immunocytochemistry (ICC), making it a versatile tool for your research needs. Its established performance in these applications ensures that you can confidently explore the role of SREBF2 in your studies.

Abcam Product Citation Summary

The data indicates that SREBF2 is being extensively studied in various human and animal models, particularly in the context of cholesterol metabolism, vascular inflammatory responses, and the effects of diet and exercise. The use of Western blotting is predominant, highlighting its importance in protein detection for these studies.

Abcam Product Citation Table

Function

Sterol regulatory element-binding protein 2

Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis (PubMed:32322062).

Processed sterol regulatory element-binding protein 2

Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis (PubMed:12177166, PubMed:32322062). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:7903453). Regulates transcription of genes related to cholesterol synthesis pathway (PubMed:12177166, PubMed:32322062).

Post-translational modifications

Sterol regulatory element-binding protein 2

Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). 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, releasing the transcription factor from the Golgi membrane (PubMed:10805775, PubMed:9651382). Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux (PubMed:8643593).

Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.

Processed sterol regulatory element-binding protein 2

Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.

Sequence Similarities

Belongs to the SREBP family.

Tissue Specificity

Ubiquitously expressed in adult and fetal tissues.

Cellular localization

• Sterol regulatory element-binding protein 2
• Endoplasmic reticulum membrane
• Multi-pass membrane protein
• Golgi apparatus membrane
• Multi-pass membrane protein
• Cytoplasmic vesicle
• COPII-coated vesicle membrane
• Multi-pass membrane protein
• At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum (PubMed:32322062). Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed (PubMed:32322062).
• Processed sterol regulatory element-binding protein 2
• Nucleus
• Transported into the nucleus with the help of importin-beta. Dimerization of the bHLH domain is a prerequisite for importin beta-dependent nuclear import.

Alternative names

BHLHD2, SREBP2, SREBF2, Sterol regulatory element-binding protein 2, SREBP-2, Class D basic helix-loop-helix protein 2, Sterol regulatory element-binding transcription factor 2, bHLHd2

Database links

swissprot:Q12772 omim:600481 entrezGene:6721

Other research areas

• Immuno-oncology