Recombinant Rat Transmembrane and coiled-coil domains protein 1 (Tmco1)
Description
Chemical Properties and Structure
Tmco1 is a transmembrane protein featuring coiled-coil domains . It is located on chromosome 1q23.3 in humans . Tmco1 acts as an endoplasmic reticulum (ER) calcium-selective channel . This protein prevents the overfilling of intracellular calcium stores and maintains calcium homeostasis in the ER .
Role in Osteoporosis
Studies have found that decreased levels of Tmco1 are associated with osteoporosis in both human and mouse subjects . In osteoporotic individuals, Tmco1 expression is significantly lower compared to healthy controls . The absence of Tmco1 impairs osteoblast differentiation and bone formation .
Tmco1 knockout mice exhibit reduced bone mass and altered bone microarchitecture, which are characteristic of osteoporosis . These mice showed a significant decrease in trabecular bone volume, bone mineral density, and cortical thickness .
Mechanism of Action in Bone Formation
Tmco1 influences bone formation through the CaMKII-HDAC4-RUNX2 signaling axis . Specifically, Tmco1-mediated calcium leak activates this signaling pathway, which is vital for osteogenesis . When Tmco1 is deficient, it disrupts ER calcium homeostasis, leading to the degradation of RUNX2, a key transcription factor for osteoblast function .
Impact on Gene Expression
In Tmco1 knockout osteoblasts, the mRNA levels of osteogenic genes such as alkaline phosphatase (Alp), osteocalcin (Ocn), and collagen type I alpha 1 (Col1) are significantly downregulated compared to control osteoblasts . This downregulation impairs osteoblast differentiation and function, further contributing to bone loss .
Association with TMCO1 Defect Syndrome
Mutations in the TMCO1 gene are linked to craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome . A homozygous mutation in TMCO1 can lead to the skipping of exon 5 during cDNA sequencing, resulting in a premature termination codon .
Clinical Significance
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Ovarian Cancer: Tmco1 regulates cell proliferation, metastasis, and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance .
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Seizures: Mutations in Tmco1 have been associated with seizures in children .
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Cerebrofaciothoracic Dysplasia: Tmco1 deficiency can cause autosomal recessive cerebrofaciothoracic dysplasia .
Data Tables
Product Specs
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Target Background
Transmembrane and coiled-coil domains protein 1 (TMCO1) is a calcium-selective channel crucial for preventing calcium store overload, thus playing a vital role in calcium homeostasis. In response to endoplasmic reticulum (ER) stress, TMCO1 assembles into a homotetramer, forming a functional calcium-selective channel that regulates ER calcium content. It is also a component of a ribosome-associated ER translocon complex involved in the transport of multi-pass membrane proteins into the ER membrane and their biogenesis. Specifically, TMCO1, along with SEC61 and TMEM147, forms a lipid-filled cavity within the translocon. TMEM147 may insert hydrophobic segments of multi-pass membrane proteins from the lumen into this central membrane cavity, a process regulated by SEC61. Similarly, TMCO1 may insert hydrophobic segments of nascent chains from the cytosol into the cavity.
