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NIPA1 Membrane Protein Introduction

Introduction of NIPA1

The NIPA1 gene consists of five exons and encodes a 329 amino acid NIPA1 protein containing nine transmembrane domains and is thought to play a role in cellular magnesium metabolism. NIPA1 typically encodes a Mg2+ transporter and the loss of function of NIPA1 establishes the basis of SP phenotype. Subcellular localization with immunofluorescence revealed that endogenous NIPA1 protein is associated with cell surface in early endosomes and various neuronal and epithelial cells. High concentrations of magnesium ions lead to a decrease of NIPA1 on the cell surface, while low concentrations of magnesium ions lead to accumulation in early endosomes and recruitment of plasma membranes. The 5' end of NIPA1 contains a polyalanine repeat of 12-13 alanine residues. Some disease phenotypes are caused by polyalanine expansion in other genes, such as ocular dystrophies and Ondine syndrome.

Basic Information of NIPA1
Protein Name Magnesium transporter NIPA1
Gene Name NIPA1
Aliases Non-imprinted in Prader-Willi/Angelman syndrome region protein 1, Spastic paraplegia 6 protein
Organism Homo sapiens (Human)
UniProt ID Q7RTP0
Transmembrane Times 9
Length (aa) 329
Sequence MGTAAAAAAAAAAAAAGEGARSPSPAAVSLGLGVAVVSSLVNGSTFVLQKKGIVRAKRRGTSYLTDIVWWAGTIAMAVGQIGNFLAYTAVPTVLVTPLGALGVPFGSILASYLLKEKLNILGKLGCLLSCAGSVVLIIHSPKSESVTTQAELEEKLTNPVFVGYLCIVLLMLLLLIFWIAPAHGPTNIMVYISICSLLGSFTVPSTKGIGLAAQDILHNNPSSQRALCLCLVLLAVLGCSIIVQFRYINKALECFDSSVFGAIYYVVFTTLVLLASAILFREWSNVGLVDFLGMACGFTTVSVGIVLIQVFKEFNFNLGEMNKSNMKTD

Function of NIPA1 Membrane Protein

The NIPA1 mutation in humans and animals causes hereditary spastic paraplegia (HSP) type 6, a neurodegenerative disorder characterized by a motor neuron phenotype. The NIPA1 allele with a long polyalanine repeat increases the risk of Amyotrophic lateral sclerosis and is associated with a younger age when the disease is independently onset. Therefore, from the genetic and biological view, NIPA1 may be a reasonable candidate gene for the treatment of Amyotrophic lateral sclerosis. In vitro studies have shown that NIPA1 is an inhibitor of bone morphogenetic protein (BMP) signaling. NIPA1 interacts with the type II BMP receptor (BMPRII) and promotes its degradation by endocytosis and lysosomal degradation. The regulation of BMP signaling by NIPA1 in Drosophila is critical for synaptic growth and regulation of axon microtubules. Therefore, loss of function of the NIPA1 mutation or NIPA1 polyalanine amplification may be important causes of synaptic and axonal developmental defects.

The figure shows the predicted secondary structure of mouse NIPA1. Two mouse mutation sites T39R and G100R corresponding to the respective human T45R and G106R mutations are shown. Fig.1 The figure shows the predicted secondary structure of mouse NIPA1. Two mouse mutation sites T39R and G100R corresponding to the respective human T45R and G106R mutations are shown. (Goytain, 2007)

Application of NIPA1 Membrane Protein in Literature

  1. Svenstrup K., et al. NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy. European Journal of Neurology. 2011, 18(9): 1197-9. PubMed ID: 21599812

    This article finds that NIPA1 mutations are found in patients with complex HSP and epilepsy may be more common in spastic paraplegia type 6 than in other forms of hereditary spastic paraplegia because NIPA1 is closely related to heredity.

  2. Goytain A., et al. NIPA1(SPG6), the basis for autosomal dominant form of hereditary spastic paraplegia, encodes a functional Mg2+ transporter. Journal of Biological Chemistry. 2007, 282(11): 8060-8. PubMed ID: 17166836

    This article suggests that NIPA1 typically encodes a Mg2+ transporter and the loss of function of NIPA1 (SPG6) due to abnormal transport of the mutant protein establishes the basis for the HSP phenotype.

  3. Arkadir D., et al. Pure hereditary spastic paraplegia due to a de-novo mutation in the NIPA1 gene. European journal of neurology. 2014, 21(1): e2. PubMed ID: 25133278

    This article reports a family with a pure form of HSP due to a de novo transition mutation in the NIPA1 gene.

  4. Blauw H.M., et al. NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis. Human Molecular Genetics. 2012, 21(11): 2497-502. PubMed ID: 22378146

    This article reveals that repeated amplification of NIPA1 polyalanine is a common risk factor for amyotrophic lateral sclerosis and disease regulation.

  5. Du J., et al. Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1. Clinical Neurology & Neurosurgery. 2011, 113(6): 480-2. PubMed ID: 21419568

    This article reports the world's first complex case of SPG6 through the presence of peripheral neuropathy, which extends the phenotype of SPG6.

NIPA1 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-NIPA1 antibody development services.


During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

  1. Goytain A, et al. (2007). NIPA1(SPG6), the basis for autosomal dominant form of hereditary spastic paraplegia, encodes a functional Mg2+ transporter. Journal of Biological Chemistry. 282(11): 8060-8.

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