Details for: USF1

Gene ID: 7391

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: USF1

Ensembl ID: ENSG00000158773

Description: upstream transcription factor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • plasmablast CL0000980
    CSI 19.27
    rCSI 15.16%
    PRS 97.42
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 6.84
    rCSI 5.27%
    PRS 98.57
  • neural progenitor cell CL0011020
    CSI 6.34
    rCSI 27.9%
    PRS 90.28
  • intermediate monocyte CL0002393
    CSI 5.63
    rCSI 8.5%
    PRS 98.83
  • precursor B cell CL0000817
    CSI 4.2
    rCSI 3.68%
    PRS 98.52
  • unswitched memory B cell CL0000970
    CSI 3.61
    rCSI 3.03%
    PRS 99.16
  • immature B cell CL0000816
    CSI 3.36
    rCSI 2.5%
    PRS 98.91
  • pro-B cell CL0000826
    CSI 3.3
    rCSI 2.73%
    PRS 97.93
  • early lymphoid progenitor CL0000936
    CSI 3.05
    rCSI 2.68%
    PRS 98.56
  • colon epithelial cell CL0011108
    CSI 2.63
    rCSI 2.75%
    PRS 96.21
  • cerebral cortex endothelial cell CL1001602
    CSI 2.61
    rCSI 4.52%
    PRS 95.16
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.5
    rCSI 2.55%
    PRS 98.89
  • common dendritic progenitor CL0001029
    CSI 2.37
    rCSI 2.98%
    PRS 98.85
  • mononuclear phagocyte CL0000113
    CSI 2.31
    rCSI 5.08%
    PRS 98.23
  • ependymal cell CL0000065
    CSI 2.15
    rCSI 4.36%
    PRS 87.26
  • large pre-B-II cell CL0000957
    CSI 1.2
    rCSI 3.42%
    PRS 96.45

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Upstream transcription factor 1, [USF1](/details-gene/7391), is a protein-coding gene located on chromosome 1q23.3. It encodes a member of the basic helix-loop-helix leucine zipper (bHLH-LZ) family of regulatory proteins. As a transcription factor, [USF1](/details-gene/7391) binds to DNA as a dimer and is involved in a wide array of cellular processes, including responses to metabolic cues like glucose and hypoxia, lipid homeostasis, and the regulation of viral transcription ([Link](https://doi.org/10.1101/gad.4.10.1730), [Link](https://doi.org/10.1099/vir.0.19335-0)). **Overall**, expression data reveals that [USF1](/details-gene/7391) has its highest significance in [plasmablasts](/details-cell/CL0000980), suggesting a critical role in the terminal differentiation of B lymphocytes. Its significant expression across various B-cell and monocyte lineage cells highlights its importance in hematopoietic development and immune function. Clinically, genetic variants in [USF1](/details-gene/7391) have been associated with familial combined hyperlipidemia ([14991056](https://doi.org/10.1038/ng1320)). ## Cellular Roles and Expression Landscape The expression profile of [USF1](/details-gene/7391) points to a primary function within the hematopoietic system, particularly along the B-cell and monocyte differentiation axes. * **B-Lymphocyte Development and Function:** The most significant expression of [USF1](/details-gene/7391) is observed in [plasmablasts](/details-cell/CL0000980) (CSI: 19.27), the immediate precursors to antibody-secreting plasma cells. This suggests [USF1](/details-gene/7391) is a key transcriptional regulator driving the final stages of B-cell maturation. Consistent with this, the gene also shows notable significance in various B-cell developmental stages, including [precursor B cells](/details-cell/CL0000817), [unswitched memory B cells](/details-cell/CL0000970), [immature B cells](/details-cell/CL0000816), and [pro-B cells](/details-cell/CL0000826). This pattern indicates a sustained role for [USF1](/details-gene/7391) throughout B-cell ontogeny. * **Myeloid Cell Regulation:** [USF1](/details-gene/7391) is also significantly expressed in several monocyte subsets, including [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 6.84) and [intermediate monocytes](/details-cell/CL0002393) (CSI: 5.63). This suggests an important function in the regulation of myeloid cell activity and differentiation within the innate immune system. * **Progenitor and Non-Immune Cells:** Beyond the immune system, [USF1](/details-gene/7391) shows significant expression in [neural progenitor cells](/details-cell/CL0011020) (CSI: 6.34) and [ependymal cells](/details-cell/CL0000065). This indicates a potential role in nervous system development or maintenance. Its presence in progenitor cells of both hematopoietic ([early lymphoid progenitor](/details-cell/CL0000936)) and neural lineages suggests a conserved function in regulating cell fate decisions. ## Pathways and Molecular Function Functional annotations for [USF1](/details-gene/7391) confirm its role as a DNA-binding transcription factor that coordinates cellular responses to metabolic and environmental signals. * **Transcriptional Regulation:** As a bHLH-LZ protein, [USF1](/details-gene/7391) functions as a sequence-specific DNA binding transcription activator ([GO:0001228](https://www.ebi.ac.uk/QuickGO/term/GO:0001228)). It is known to form both homodimers and heterodimers and binds to specific DNA sequences to positively regulate transcription from RNA polymerase II promoters ([GO:0045944](https://www.ebi.ac.uk/QuickGO/term/GO:0045944)). Its activity is central to gene expression programs involved in [Developmental biology](/details-pathway/R-HSA-1266738) and [Signaling by nuclear receptors](/details-pathway/R-HSA-9006931). * **Metabolic Homeostasis:** A prominent function of [USF1](/details-gene/7391) is its involvement in metabolic regulation. It plays a role in [Glucose homeostasis](/details-pathway/GO:0042593), [Lipid homeostasis](/details-pathway/GO:0055088), and the [cellular response to glucose stimulus](/details-pathway/GO:0071333). This molecular function is consistent with its clinical association with familial combined hyperlipidemia ([14991056](https://doi.org/10.1038/ng1320)). * **Viral Interaction:** [USF1](/details-gene/7391) is implicated in [Late viral transcription](/details-pathway/GO:0019086). Research has shown it can be co-opted by viruses, such as the Varicella-zoster virus, where it interacts with viral proteins to promote viral replication ([Link](https://doi.org/10.1099/vir.0.19335-0)). This highlights its role as a host factor that can influence the lifecycle of certain pathogens. ## Research Directions The available data suggests several avenues for future investigation into the roles of [USF1](/details-gene/7391) in immunity, development, and disease. **Proposed Hypotheses:** 1. Given its peak significance in [plasmablasts](/details-cell/CL0000980) and its role in metabolic regulation, [USF1](/details-gene/7391) may act as a master regulator that couples the metabolic reprogramming necessary for massive immunoglobulin synthesis with the transcriptional program of terminal B-cell differentiation. 2. The significant expression of [USF1](/details-gene/7391) in both hematopoietic and [neural progenitor cells](/details-cell/CL0011020) suggests it may function as a conserved regulator of lineage commitment, potentially by integrating metabolic status with developmental signaling pathways in diverse progenitor populations. 3. The interaction of [USF1](/details-gene/7391) with viral transactivators suggests it is a crucial host dependency factor for certain viruses. Its inhibition in infected cells could represent a novel antiviral strategy. **Experimental Approach:** To test the hypothesis that [USF1](/details-gene/7391) is essential for plasmablast differentiation and function, a B-cell specific conditional knockout of *Usf1* in mice could be generated. Splenic B-cells from these mice and wild-type littermates could be isolated and stimulated *ex vivo* with LPS and IL-4 to induce plasmablast differentiation. The experimental readout would involve quantifying plasmablast populations via flow cytometry (CD138+), measuring immunoglobulin secretion by ELISA, and performing RNA-sequencing to identify the [USF1](/details-gene/7391)-dependent gene networks that govern this process. **Therapeutic Potential:** As an intracellular transcription factor, [USF1](/details-gene/7391) is a challenging target for conventional biologics like antibodies. However, its role in lipid metabolism and its high expression in [plasmablasts](/details-cell/CL0000980) suggests that targeting its activity could be relevant for metabolic disorders and plasma cell dyscrasias like multiple myeloma. Therapeutic strategies would likely require novel modalities, such as antisense oligonucleotides or small molecule inhibitors designed to disrupt its dimerization or DNA-binding activity. Given its role as a transcriptional activator, inhibition of [USF1](/details-gene/7391) function would be the primary therapeutic objective.

Genular Protein ID: 1770217218

Symbol: USF1_HUMAN

Name: Upstream stimulatory factor 1

UniProtKB Accession Codes:

P22415 B2RBZ4 Q5SY46 Q7Z5Y1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 2 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 32 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 3 SASBDB 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2249772

Title: The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer.

PubMed ID: 2249772

DOI: 10.1101/gad.4.10.1730

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14573800

Title: Transcription factor USF, expressed during the entire phase of Varicella-zoster virus infection, interacts physically with the major viral transactivator IE62 and plays a significant role in virus replication.

PubMed ID: 14573800

DOI: 10.1099/vir.0.19335-0

PubMed ID: 25218447

Title: Uncovering global SUMOylation signaling networks in a site-specific manner.

PubMed ID: 25218447

DOI: 10.1038/nsmb.2890

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 8306960

Title: Structure and function of the b/HLH/Z domain of USF.

PubMed ID: 8306960

DOI: 10.1002/j.1460-2075.1994.tb06247.x

PubMed ID: 14991056

Title: Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1).

PubMed ID: 14991056

DOI: 10.1038/ng1320

Sequence Information:

  • Length: 310
  • Mass: 33538
  • Checksum: BFDA91519B4B80AE
  • Sequence:
    • MKGQQKTAET EEGTVQIQEG AVATGEDPTS VAIASIQSAA TFPDPNVKYV FRTENGGQVM 
YRVIQVSEGQ LDGQTEGTGA ISGYPATQSM TQAVIQGAFT SDDAVDTEGT AAETHYTYFP 
STAVGDGAGG TTSGSTAAVV TTQGSEALLG QATPPGTGQF FVMMSPQEVL QGGSQRSIAP 
RTHPYSPKSE APRTTRDEKR RAQHNEVERR RRDKINNWIV QLSKIIPDCS MESTKSGQSK 
GGILSKACDY IQELRQSNHR LSEELQGLDQ LQLDNDVLRQ QVEDLKNKNL LLRAQLRHHG 
LEVVIKNDSN