SMN2
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN) due to inactivating mutations in the encoding gene SMN1. A second duplicated gene,SMN2, produces very little but sufficient functional protein for survival. Humans have 2 nearly identical inverted SMN genes on chromosome 5q13, SMN1, the telomeric copy of the SMN gene, and SMN2, the centromeric copy, differ by only 5 base pairs, and the coding sequence differs by a single nucleotide. In contrast to SMN1, which predominantly produces full length SMN protein, the SMN2 gene produces predominantly a shortened, unstable, and rapidly degraded isoform.
Full length SMN protein is a ubiquitously expressed 294 amino acid polypeptide. The SMN protein is ubiquitously expressed and is localized in the cytoplasm, neuronal growth cones, neuronal extensions, the nucleolus and in punctate nuclear structures called Gemini of coiled bodies (Gems) and Cajal bodies. The SMN protein has thus been attributed several key regulatory cellular functions in neuronal cells, including roles in RNA metabolism [specifically small nuclear ribonucleoproteins (snRNPs)], actin cytoskeleton dynamics, mRNA transport, ubiquitin homeostasis, bioenergetics pathways and synaptic vesicle release. The RhoA-ROCK pathway is aberrantly upregulated in SMN-depleted rodent neuronal cells and in the spinal cord and skeletal muscle of Smn2B/– mice. The increased activity of the RhoA-ROCK pathway in SMA mice induces the increased phosphorylation of PTEN. The ubiquitin-like modifier activating enzyme Uba1 and its downstream effectors [including the Wnt signaling effector β-catenin (Ctnnb1)], have been identified as major targets acting downstream of SMN to regulate neuromuscular.
References
1.Arnold WD,et al. Muscle Nerve. 2015;51(2):157–167.
Full length SMN protein is a ubiquitously expressed 294 amino acid polypeptide. The SMN protein is ubiquitously expressed and is localized in the cytoplasm, neuronal growth cones, neuronal extensions, the nucleolus and in punctate nuclear structures called Gemini of coiled bodies (Gems) and Cajal bodies. The SMN protein has thus been attributed several key regulatory cellular functions in neuronal cells, including roles in RNA metabolism [specifically small nuclear ribonucleoproteins (snRNPs)], actin cytoskeleton dynamics, mRNA transport, ubiquitin homeostasis, bioenergetics pathways and synaptic vesicle release. The RhoA-ROCK pathway is aberrantly upregulated in SMN-depleted rodent neuronal cells and in the spinal cord and skeletal muscle of Smn2B/– mice. The increased activity of the RhoA-ROCK pathway in SMA mice induces the increased phosphorylation of PTEN. The ubiquitin-like modifier activating enzyme Uba1 and its downstream effectors [including the Wnt signaling effector β-catenin (Ctnnb1)], have been identified as major targets acting downstream of SMN to regulate neuromuscular.
References
1.Arnold WD,et al. Muscle Nerve. 2015;51(2):157–167.
Others
SMN2
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LMI-070
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RG7800
产品货号 : M11934
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D-156844
产品货号 : M10049
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