BMPR1A Human

Bone Morphogenetic Protein Receptor Type IA Human Recombinant
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Description

Gene and Protein Details

FeatureDetails
Gene SymbolBMPR1A
Chromosomal Location10q23.2
Protein NameBone Morphogenetic Protein Receptor Type IA
UniProt IDP36894
Molecular Weight80.8 kDa (glycosylated homodimer)
DomainsExtracellular ligand-binding domain, transmembrane region, kinase domain

The BMPR1A gene spans 27 exons and encodes a 532-amino acid protein. It forms heterotetrameric complexes with BMPR2 upon ligand binding, initiating downstream signaling .

Ligand Interactions

  • Agonists: BMP2, BMP4, BMP6, BMP7, GDF6

  • Antagonists: Noggin, Chordin

BMPR1A activates SMAD1/5/8 proteins, which complex with SMAD4 to regulate transcription of genes involved in:

  • Cell proliferation

  • Osteoblast differentiation

  • Adipogenesis

  • Neural stem cell fate determination

Key Signaling Mechanisms

  • Canonical Pathway: BMPR1A phosphorylates SMADs, enabling nuclear translocation for gene regulation .

  • Non-Canonical Pathways: Modulates MAPK and PI3K/AKT pathways in tissue-specific contexts .

Genetic Disorders Linked to BMPR1A

DiseaseMechanismClinical Features
Juvenile Polyposis SyndromeLoss-of-function mutations impair SMAD signalingGastrointestinal polyps, cancer risk
Cowden SyndromePTEN-BMPR1A-SMAD4 axis disruptionHamartomas, breast/thyroid cancers
Congenital Pulmonary Airway MalformationMesenchymal BMPR1A deficiencyPrenatal lung cysts, reduced airway SMCs

Cancer Implications

  • Breast/Colon Carcinoma: Somatic mutations correlate with tumor progression .

  • Leukemia: Altered BMPR1A expression linked to B-lymphoblastic leukemia .

Biotechnological Synthesis

  • Expression System: CHO cells yield glycosylated, bioactive homodimers .

  • Purification: Affinity chromatography ensures >95% purity .

  • Stability: Lyophilized form stable at -18°C; reconstituted protein usable for 7 days at 4°C .

Therapeutic Potential

  • Bone Regeneration: Enhances osteoblast extracellular matrix deposition .

  • Neural Repair: Palmitoylation at C180 regulates oligodendrocyte differentiation .

  • Cancer Therapy: Inhibitors like LDN-193189 block BMPR1A in preclinical models .

Key Studies

  1. Myeloid BMPR1A in Cancer

    • Deletion in myeloid cells (LysMCre mice) reduces prostate tumor growth via altered monocyte/neutrophil dynamics .

  2. Germinal Center Regulation

    • Bmpr1a-deficient B cells show impaired plasma cell differentiation, reducing long-term antibody production .

  3. Lung Development

    • Mesenchymal Bmpr1a knockout disrupts airway smooth muscle growth, mimicking human CPAM pathology .

Tissue-Specific Expression

  • High: Lung, bone marrow, spleen .

  • Low: Liver, thyroid .

Post-Translational Modifications

  • Palmitoylation: At Cys180 directs receptor trafficking; mutations reduce surface expression in neural stem cells .

  • Phosphorylation: Activates kinase domain for SMAD recruitment .

Inhibitors and Drug Development

InhibitorTargetClinical StageReference
LDN-193189BMPR1A/ALK2Preclinical
ML347ALK3 (BMPR1A)Preclinical
DMH1BMPR1A/ALK2Preclinical

Future Directions

  • Gene Therapy: CRISPR-edited BMPR1A for polyposis management .

  • Stem Cell Engineering: Optimizing BMPR1A signaling to enhance oligodendrocyte generation .

Product Specs

Introduction

Bone morphogenetic protein (BMP) receptors are transmembrane serine/threonine kinases. This family includes type I receptors BMPR1A and BMPR1B, and the type II receptor BMPR2. These receptors are structurally similar to ACVR1 and ACVR2 receptors. Ligands for these receptors belong to the TGF-beta superfamily. TGF-betas initiate signal transduction by forming heteromeric complexes with two different types of serine/threonine kinase receptors: type I receptors (approximately 50-55 kDa) and type II receptors (approximately 70-80 kDa). Type II receptors can bind ligands independently of type I receptors. However, they require type I receptors for signaling. Conversely, type I receptors rely on type II receptors for ligand binding.

Description
Recombinant human BMPR1A extracellular domain is produced in baculovirus. It is a monomeric, glycosylated polypeptide chain with a C-terminal 6xHis tag. This protein has a molecular weight of 23 kDa.
BMR1A is purified using proprietary chromatographic techniques.
Physical Appearance
Sterile Filtered White lyophilized powder.
Formulation
CD292 was lyophilized from a sterile solution (1mg/ml) containing 1X PBS.
Solubility
Reconstitute the lyophilized ALK-3 in sterile PBS at a minimum concentration of 100 µg/ml. This solution can be further diluted with other aqueous solutions.
Stability
Lyophilized Bone Morphogenetic Protein Receptor 1A remains stable at room temperature for 3 weeks. However, it is recommended to store it desiccated below
-18°C. After reconstitution, store BMPR1A at 4°C for 2-7 days. For long-term storage, keep it at -18°C.
Adding a carrier protein (0.1% HSA or BSA) is recommended for long-term storage.
Avoid repeated freeze-thaw cycles.
Purity
The purity is determined using the following methods:
(a) RP-HPLC analysis.
(b) SDS-PAGE analysis.
The purity is greater than 90.0%.
Biological Activity
The biological activity is evaluated by the ability to inhibit recombinant human BMP-2 induced alkaline phosphatase production in C2C12 myogenic cells. Typically, the ED50 for this effect is 1-3 µg/ml in the presence of 500 ng/ml recombinant human BMP-2, corresponding to a Specific Activity of 2,000 units/mg.
Synonyms

BMPR-1A, BMP-R1A, BMPR1A, BMR1A, CD292, CD-292, Serine/threonine-protein kinase receptor R5, SKR5, ALK-3, ACVRLK3, EC 2.7.11.30, CD292 antigen.

Source
Insect Cells.

Product Science Overview

Introduction

Bone Morphogenetic Protein Receptor Type IA (BMPR1A), also known as Activin Receptor-Like Kinase 3 (ALK3), is a crucial component of the transforming growth factor-beta (TGF-β) superfamily. This receptor is a transmembrane serine/threonine kinase that plays a significant role in various biological processes, including embryonic development, bone formation, and cellular differentiation .

Structure and Function

BMPR1A is a type I receptor that forms a heteromeric complex with type II receptors upon ligand binding. This complex is essential for the signal transduction of bone morphogenetic proteins (BMPs), which are key regulators of bone and cartilage development . The receptor’s structure includes an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular serine/threonine kinase domain .

Biological Significance

BMPR1A is involved in numerous developmental processes. It is crucial for dorso-ventral patterning, neural crest development, and organogenesis, including the development of the heart, kidneys, and thymus . Additionally, BMPR1A plays a role in chondrogenesis, skeletal development, and hematopoiesis .

Recombinant BMPR1A

Recombinant BMPR1A is produced using recombinant DNA technology, which involves inserting the BMPR1A gene into an expression vector and introducing it into a host cell, such as E. coli or mammalian cells. The host cells then produce the BMPR1A protein, which can be purified and used for various research and therapeutic applications .

Applications

Recombinant BMPR1A is widely used in research to study BMP signaling pathways and their roles in development and disease. It is also utilized in therapeutic applications, such as tissue engineering and regenerative medicine, where it can promote bone and cartilage repair .

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