SMN-Sm protein complex
Definition
Target type: cellularcomponent
A protein complex formed by the association of several methylated Sm proteins with the SMN complex; the latter contains the survival motor neuron (SMN) protein and at least eight additional integral components, including the Gemin2-8 and unrip proteins; additional proteins, including galectin-1 and galectin-3, are also found in the SMN-SM complex. The SMN-Sm complex is involved in spliceosomal snRNP assembly in the cytoplasm. [GOC:vw, PMID:11522829, PMID:17401408]
The SMN-Sm protein complex is a dynamic assembly that plays a critical role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome. The complex is primarily localized in the cytoplasm, but also shuttles between the cytoplasm and nucleus. It comprises the Survival of Motor Neuron (SMN) protein, which is the central scaffold of the complex, and seven Sm proteins: SmB, SmD1, SmD2, SmD3, SmE, SmF, and SmG. These proteins assemble into a heptameric ring structure, termed the Sm ring, which recognizes and binds to a conserved Sm site present in the snRNA.
The SMN complex functions in a multi-step process to assemble snRNPs. First, the Sm proteins assemble into the Sm ring, facilitated by the SMN protein. This ring then binds to the Sm site of the snRNA, forming the Sm core domain of the snRNP. Subsequently, other snRNP-specific proteins, including Sm-like proteins (LSm) and the U snRNP-associated proteins (U proteins), are recruited to the complex.
The assembly of the snRNP occurs in a stepwise manner, with the SMN complex acting as a chaperone. It facilitates the proper folding of the snRNA and ensures the correct stoichiometry of the Sm proteins. After the snRNP is fully assembled, it is transported to the nucleus, where it participates in pre-mRNA splicing.
The SMN complex is essential for cell viability. Mutations in the SMN gene, which encodes the SMN protein, lead to Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease characterized by progressive muscle weakness and atrophy. This highlights the importance of the SMN complex in maintaining normal cellular function.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Survival motor neuron protein | A survival motor neuron protein that is encoded in the genome of human. [PRO:DAN, UniProtKB:Q16637] | Homo sapiens (human) |
| Gem-associated protein 4 | A gem-associated protein 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P57678] | Homo sapiens (human) |
Compounds (3)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| indoprofen | indoprofen : A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(1-oxo-1,3-dihydroisoindol-2-yl)phenyl group. Initially used as an anti-inflammatory and analgesic, it was withdrawn from the market due to causing severe gastrointestinal bleeding. It has been subsequently found to increase production of the survival motor neuron protein. Indoprofen: A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21) | gamma-lactam; isoindoles; monocarboxylic acid | EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| 1-[4-(4-bromophenyl)-2-thiazolyl]-4-piperidinecarboxamide | piperidinecarboxamide | ||
| dehydrocurvularin |