| http://purl.uniprot.org/citations/18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18165682 | http://www.w3.org/2000/01/rdf-schema#comment | "Dok-7 is a cytoplasmic activator of muscle-specific receptor-tyrosine kinase (MuSK). Both Dok-7 and MuSK are required for neuromuscular synaptogenesis. Mutations in DOK7 underlie a congenital myasthenic syndrome (CMS) associated with small and simplified neuromuscular synapses likely due to impaired Dok-7/MuSK signaling. The overwhelming majority of patients with DOK7 CMS have at least one allele with a frameshift mutation that causes a truncation in the COOH-terminal region of Dok-7 and affects MuSK activation. Dok-7 has pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains in the NH2-terminal moiety, both of which are indispensable for MuSK activation in myotubes, but little is known about additional functional elements. Here, we identify a chromosome region maintenance 1-dependent nuclear export signal (NES) in the COOH-terminal moiety and demonstrate that the NES-mediated cytoplasmic location of Dok-7 is essential for regulating the interaction with MuSK in myotubes. The NH2-terminal PH domain is responsible for the nuclear import of Dok-7. We also show that the Src homology 2 target motifs in the COOH-terminal moiety of Dok-7 are active and crucial for MuSK activation in myotubes. In addition, CMS-associated missense mutations found in the PH or PTB domain inactivate Dok-7. Together, these findings demonstrate that, in addition to the NH2-terminal PH and PTB domains, the COOH-terminal NES and Src homology 2 target motifs play key roles in Dok-7/MuSK signaling for neuromuscular synaptogenesis. Ablation or disruption of these functional elements in Dok-7 probably underlies the neuromuscular junction synaptopathy observed in DOK7 CMS."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m708607200"xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Iemura S."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Okada K."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Natsume T."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Yamanashi Y."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Ueno M."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Beeson D."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Higuchi O."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Spearman H."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/author | "Hamuro J."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/pages | "5518-5524"xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/title | "Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7."xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://purl.uniprot.org/core/volume | "283"xsd:string |
| http://purl.uniprot.org/citations/18165682 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18165682 |
| http://purl.uniprot.org/citations/18165682 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18165682 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J0R2-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |
| http://purl.uniprot.org/uniprot/#_A0A087WSY1-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |
| http://purl.uniprot.org/uniprot/#_A0A1W2PRA3-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |
| http://purl.uniprot.org/uniprot/#_A7E2S0-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |
| http://purl.uniprot.org/uniprot/#_O15146-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |
| http://purl.uniprot.org/uniprot/#_E9PVV8-mappedCitation-18165682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18165682 |