PRRX1 Human

Paired Related Homeobox 1 Human Recombinant
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Description

Developmental Functions

  • Regulates mesenchymal stem cell differentiation via TGF-β and TNF-α signaling

  • Essential for vascular and cardiac morphogenesis; Prrx1-null mice exhibit aortic arch malformations

  • Mediates epithelial-to-mesenchymal transition (EMT) during embryogenesis

Atrial Fibrillation (AF)

MechanismKey FindingsSources
Loss-of-function mutationsReduce transactivation of SHOX2 and ISL1, shortening atrial action potential duration
Enhancer dysfunctionrs3903239 variant diminishes PRRX1 expression in cardiomyocytes, increasing AF risk

Cancer

Cancer TypeRole of PRRX1Clinical ImpactSources
Colorectal Liver MetastasesUpregulates TIM-3 and VISTA, creating immunosuppressive microenvironmentPoor prognosis
SarcomasPromotes proliferation via interaction with TOP2A; knockdown reduces tumorigenicityChemoresistance
Stromal FibroblastsDrives myofibroblastic phenotype via super-enhancer remodelingEnhances tumor aggressiveness

Cardiovascular Research

  • Functional Validation:

    • PRRX1 mutations reduced promoter activity of SHOX2 by 52.4% and ISL1 by 64.7% in luciferase assays .

    • Zebrafish models with PRRX1 suppression showed 23% shorter atrial action potential duration .

  • Electrophysiological Effects:

    • Reduced PRRX1 decreases peak sodium current density (↓28%) and atrial conduction velocity (↓19%) .

Oncology Research

  • Fibroblast Reprogramming:

    • PRRX1-high CAFs exhibit 3.2-fold higher ECM contraction than PRRX1-low subpopulations .

    • Depletion of PRRX1 in CAFs induces tumor remission in mouse models .

  • Immune Modulation:

    • PRRX1-high tumors correlate with elevated CD163+ M2 macrophages (r=0.71, p<0.001) .

Clinical and Therapeutic Implications

  • Biomarker Potential:

    • PRRX1 expression in CAFs predicts unfavorable outcomes in lung, colon, and ovarian cancers (HR=2.1, p=0.003) .

    • rs577676 SNP associated with 1.4-fold increased AF risk in genome-wide studies .

  • Therapeutic Targets:

    • Targeting PRRX1-TGF-β axis in fibroblasts reduces tumor growth in preclinical models .

    • Inhibitors of TIM-3/VISTA may benefit PRRX1-high colorectal metastases .

Product Specs

Introduction
PRRX1 is a member of the paired family of homeobox proteins and acts as a transcription co-activator. It enhances the DNA-binding activity of serum response factor, which is essential for gene induction by growth and differentiation factors. PRRX1 also plays a role in regulating muscle creatine kinase, contributing to the development of various mesodermal muscle types. This protein binds to an A/T-rich element within the muscle creatine enhancer. Notably, PRRX1 has been associated with diseases such as agnathia-otocephaly complex and pleomorphic liposarcoma.
Description
Recombinant human PRRX1, expressed in E. coli, is a single, non-glycosylated polypeptide chain. It consists of 241 amino acids (residues 1-217) and has a molecular weight of 26.9 kDa. This protein includes a 24 amino acid His-tag at the N-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A clear, sterile-filtered solution.
Formulation
The PRRX1 protein solution (0.25 mg/ml) is supplied in a buffer containing 20 mM Tris-HCl (pH 8.0), 0.2 M NaCl, 50% glycerol, and 2 mM DTT.
Stability
For short-term storage (up to 2-4 weeks), the product can be stored at 4°C. For extended storage, it is recommended to freeze at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is advised for long-term storage. It is important to avoid repeated freeze-thaw cycles.
Purity
The purity of the protein is determined to be greater than 85.0% by SDS-PAGE analysis.
Synonyms
AGOTC, PHOX1, PMX1, PRX-1, PRX1, Paired mesoderm homeobox protein 1, Homeobox protein PHOX1, Paired-related homeobox protein 1, PRRX1.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSHMTSSYG HVLERQPALG GRLDSPGNLD TLQAKKNFSV SHLLDLEEAG DMVAAQADEN VGEAGRSLLE SPGLTSGSDT PQQDNDQLNS EEKKKRKQRR NRTTFNSSQL QALERVFERT HYPDAFVRED LARRVNLTEA RVQVWFQNRR AKFRRNERAM LANKNASLLK SYSGDVTAVE QPIVPRPAPR PTDYLSWGTA SPYRSSSLPR CCLHEGLHNG F

Product Science Overview

Gene and Protein Structure

The PRRX1 gene is located on chromosome 1q24.2 in humans . It encodes a DNA-associated protein that functions as a transcription coactivator. This protein enhances the DNA-binding activity of serum response factor (SRF), a protein required for the induction of genes by growth and differentiation factors . The PRRX1 gene undergoes alternative splicing, resulting in two isoforms that differ in their abundance and expression patterns .

Biological Functions

PRRX1 plays a crucial role in various biological processes, including:

  • Embryonic Development: PRRX1 is involved in the morphogenesis of the embryonic skeletal system, limb development, and craniofacial development .
  • Mesenchymal Stem Cell Differentiation: PRRX1 expression is restricted to the mesoderm during embryonic development and is expressed in mesenchymal tissues in adult mice . It regulates the differentiation of mesenchymal precursors, which are essential for the formation of various tissues, including cartilage and bone .
  • Transcription Regulation: As a transcription coactivator, PRRX1 enhances the DNA-binding activity of SRF, thereby regulating the expression of genes involved in growth and differentiation .
Clinical Significance

Recent studies have highlighted the role of PRRX1 in various diseases and conditions:

  • Pulmonary Fibrosis: PRRX1 has been identified as a key mesenchymal transcription factor in pulmonary fibrosis. It is strongly expressed by lung fibroblasts and is regulated by a balance of TGF-β and PGE2 .
  • Stem Cell Maintenance: PRRX1 is required for the maintenance of stemness in adult neural stem cells (NSCs) by associating with the transcription factor SOX2 .
  • Cell Cycle Regulation: PRRX1 regulates quiescence in human oligodendrocyte progenitor cells (hOPCs) by inducing reversible G1/0 arrest .
Research and Applications

The recombinant form of PRRX1 is used in various research applications to study its role in development, disease, and stem cell biology. Understanding the functions and mechanisms of PRRX1 can provide insights into potential therapeutic targets for diseases such as pulmonary fibrosis and other conditions involving mesenchymal cell differentiation.

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