Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive degeneration of motoneurons in spinal cord and brainstem. The telomeric copy of a duplicated gene termed survival motor neuron (smn), which maps to chromosome 5q13, has been found to be deleted in most patients. The encoded gene product is a novel protein which recently has been shown to accumulate in specific nuclear organelles (gemini of coiled bodies, GEMS), and to play a part in the formation of the spliceosome complex. We have cloned and sequenced the rat smn cDNA. Antibodies generated against an N-terminus peptide recognized a main protein of 32 kDa in immunoblots of rat embryonic tissue extracts. Minor bands of 35 kDa, 45 kDa and, in perinatal muscle, of 24 kDa were also specifically detected, indicating that SMN is expressed as different molecular forms. Subcellular fractionation indicated that the 32 kDa form is mainly soluble, while the 35 kDa and 45 kDa products segregate to the microsomal-mitochondrial fraction. SMN protein is highly regulated during development: expression is high in embryonic tissues (central nervous system, muscle, lung and liver), and then progressively decreases to very low levels in most tissues of the adult. The demonstration of different molecular forms of SMN along with its developmental regulation may help to understand the contribution of this protein in the appearance of SMA phenotype.
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PMID:Survival motor neuron (SMN) protein in rat is expressed as different molecular forms and is developmentally regulated. 975 61

The survival motor neuron (SMN) gene is deleted or mutated in over 98% of spinal muscular atrophy patients who show specific motoneuron loss. By performing transfection experiments with rat smn cDNA, we show that two isoforms of SMN with Mr of 32 kDa and 35 kDa are produced by the same cDNA. In cultured motoneurons, both forms colocalize in coiled bodies and not in GEMS bodies as shown for HeLa cells. Subcellular fractionation of cells acutely dissociated from rat embryonic ventral spinal cord shows that the two SMN isoforms have a different subcellular localization, namely, that the 32 kDa isoform is enriched in the cytosol, whereas the 35 kDa isoform is segregating in the microsomal fraction. We show that the 35 kDa isoform of SMN is part of an insoluble complex but is absent from the cytoplasmic membranes and from the mitochondria. Immunostaining studies show that neither SMN isoform colocalizes with Bcl-2, the mitochondrial antiapoptotic protein suggested to bind to SMN in HeLa cells. Our results show that the isoforms of SMN protein have different subcellular localization and may therefore play independent biological roles. Moreover, the absence of colocalization of SMN with Bcl-2 in motoneurons suggests that some of the interactors of SMN may vary depending on the cell type, and this underscores the importance of identifying motoneuron-specific SMN interactors.
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PMID:Expression and subcellular localization of two isoforms of the survival motor neuron protein in different cell types. 1105 3

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive loss of the spinal motoneurons. The SMA-determining gene has been termed survival motor neuron (SMN) and is deleted or mutated in over 98% of patients. The encoded gene product is a protein expressed as different isoforms. In particular, we showed that the rat SMN cDNA produces two isoforms with M(r) of 32 and 35kDa, both localized in nuclear coiled bodies, but the 32kDa form is also cytoplasmic, whereas the 35kDa form is also microsomal. To determine the molecular relationship between these two isoforms and potential post-translational modifications, we performed transfection experiments with a double-tagged rat SMN. Immunoblot and immunostaining studies demonstrated that the 32kDa SMN isoform derives from the full length 35kDa, through a proteolytic cleavage at the C-terminal. Furthermore, the 35kDa SMN isoform is physiologically phosphorylated in vivo. This may modulate its interaction with molecular partners, either proteins or nucleic acids.
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PMID:Post-translational modifications in the survival motor neuron protein. 1546 16