USF1 — Upstream Transcription Factor 1

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USF1 Gene

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USF1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">USF1 — Upstream Transcription Factor 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>USF1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Upstream Stimulatory Factor 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1q22</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7399</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000158710</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P22415</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>191323</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>2,412 bp</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>310 amino acids</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Adipose tissue</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brain ([cortex](/brain-regions/cortex), hippocampus)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Pancreas</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Type</td>
</tr>
<tr>
<td class="label">USF2</td>
<td>Partner TF</td>
</tr>
<tr>
<td class="label">CBP/p300</td>
<td>Coactivator</td>
</tr>
<tr>
<td class="label">HDAC1/2</td>
<td>Corepressor</td>
</tr>
<tr>
<td class="label">NRF2</td>
<td>Partner TF</td>
</tr>
<tr>
<td class="label">REST</td>
<td>Partner TF</td>
</tr>
<tr>
<td class="label">SIRT1</td>
<td>Deacetylase</td>
</tr>
<tr>
<td class="label">PGC-1α</td>
<td>Coactivator</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/ataxia" style="color:#ef9a9a">Ataxia</a>, <a href="/wiki/dystonia" style="color:#ef9a9a">Dystonia</a>, <a href="/wiki/huntington" style="color:#ef9a9a">Huntington</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">20 edges</a></td>
</tr>
</table>

Introduction

Usf1 — Upstream Transcription Factor 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Mermaid diagram (expand to render)

USF1 (Upstream Stimulatory Factor 1) encodes a transcription factor belonging to the basic helix-loop-helix leucine zipper (bHLH-LZ) family. The USF1 protein plays crucial roles in regulating genes involved in lipid metabolism, glucose homeostasis, cell cycle progression, stress responses, and circadian rhythm. It has been implicated in Alzheimer's disease, cardiovascular disease, and various metabolic disorders["@viollet1996"].

Gene Information

Protein Structure

The USF1 protein contains functional domains essential for its transcriptional activity[@viollet1996]:

Functional Domains

Basic region: N-terminal DNA-binding domain that recognizes E-box sequences (CANNTG)
Helix-loop-helix (HLH) domain: Mediates protein-protein interactions and dimerization
Leucine zipper (LZ) motif: Additional dimer stabilization through hydrophobic interactions
Transactivation domain: C-terminal region that interacts with coactivators

Isoforms

USF1 has multiple splice variants:

USF1 isoform 1: Full-length 310 amino acids (canonical)
USF1 isoform 2: Alternative splicing, functional differences

Biological Functions

USF1 functions as a transcriptional regulator with broad target gene specificity[@viollet1996]:

Metabolic Regulation

Lipid metabolism

Fatty acid synthesis (ACC, FAS)
Cholesterol homeostasis (HMG-CoA reductase)
Lipoprotein metabolism

Glucose homeostasis

Gluconeogenesis (PEPCK, G6Pase)
Glycolysis (PFK, LDH)
Insulin signaling

Cellular Processes

Cell cycle regulation

Cyclin D expression
CDK inhibitor regulation
Cell proliferation

Stress response

Heat shock protein expression
Antioxidant gene regulation (SOD, catalase)
DNA damage response

Circadian rhythm

Clock gene regulation
Metabolic gene oscillation
Sleep-wake cycle

Expression Pattern

In the brain, USF1 is expressed in:

Cerebral cortex ([neurons](/entities/neurons), glia)
[Hippocampus](/brain-regions/hippocampus) (CA1-CA3, dentate gyrus)
Cerebellum (Purkinje cells)
Basal ganglia

Disease Associations

Alzheimer's Disease

USF1 is implicated in Alzheimer's disease through multiple mechanisms[@liu2002]:

[Amyloid precursor protein](/entities/app-protein) (APP) metabolism: Regulates APP gene expression and processing
Lipid rafts: Modulates cholesterol content affecting amyloidogenesis
Synaptic function: Controls genes involved in synaptic plasticity
Neuroinflammation: Regulates inflammatory cytokine expression
Circadian disruption: Alters circadian clock gene expression in AD brain

Cardiovascular Disease

Atherosclerosis: Regulates cholesterol efflux genes
Hyperlipidemia: Triglyceride metabolism dysregulation
Cardiac hypertrophy: Stress response gene regulation

Metabolic Syndrome

Type 2 diabetes: Insulin signaling gene regulation
Obesity: Adipocyte gene expression
Fatty liver disease: Hepatic lipid metabolism

Cancer

Colorectal cancer: Altered expression and mutations
Breast cancer: Prognostic marker potential
Hematological malignancies: Lymphomagenesis

Interaction Network

USF1 interacts with:

Clinical Significance

Genetic Variants

Promoter polymorphisms: Associated with lipid levels and CAD risk
SNPs: Linkage with metabolic syndrome phenotypes

Therapeutic Targets

Metabolic disorders: USF1 modulators for dyslipidemia

Neurodegeneration: Understanding AD/PD mechanisms

Cancer: Biomarker and potential target

Key Publications

Viollet B, et al. (1996). "The transcription factor USF1 regulates gene expression." Journal of Biological Chemistry. PMID: 8621685(https://pubmed.ncbi.nlm.nih.gov/8621685/).

Liu L, et al. (2002). "USF1 and cholesterol metabolism in Alzheimer's disease." Journal of Alzheimer's Disease. PMID: 12214107(https://pubmed.ncbi.nlm.nih.gov/12214107/).

Caswell CC, et al. (2009). "The bHLH-LZ transcription factor USF1." Cellular and Molecular Life Sciences. PMID: 19151984(https://pubmed.ncbi.nlm.nih.gov/19151984/).

Background

The study of Usf1 — Upstream Transcription Factor 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

[Viollet B, et al, (1996) (1996)](https://pubmed.ncbi.nlm.nih.gov/8621685/)

[Liu L, et al, (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/12214107/)

Pathway Diagram

The following diagram shows the key molecular relationships involving USF1 — Upstream Transcription Factor 1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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USF1 — Upstream Transcription Factor 1

USF1 Gene

USF1 Gene

Introduction

Overview

Gene Information

Protein Structure

Functional Domains

Isoforms

Biological Functions

Metabolic Regulation

Cellular Processes

Expression Pattern

Disease Associations

Alzheimer's Disease

Cardiovascular Disease

Metabolic Syndrome

Cancer

Interaction Network

Clinical Significance

Genetic Variants

Therapeutic Targets

Key Publications

See Also

Background

External Links

References

Pathway Diagram