MAP3K10: Human mitogen-activated protein kinase kinase kinase 10 (SH3 domain)
PDB Code: 2RF0
The mixed lineage kinase MAP3K10 belongs to the TKL ( Tyrosine Kinase Like) family of serine threonine kinases. The full-length protein consists of an N-terminal SH3 domain, a kinase catalytic domain, a double leucine zipper motif and a Rac/Cdc42 GTPase-binding (CRIB) motif .
MAP3K10 has been linked to a number of diverse cellular functions including a proposed role in neuronal apoptosis, in enhancement of trans-repression of alien and nuclear receptors, a function in vesicle formation and in endosome recycling by binding to clathrin. In addition, MAP3K10 has been suggested to be involved in neuronal toxicity induced by polyglutamine-expanded huntingtin as observed in Huntington disease and other neurodegenerative diseases.
Here we determined the structure of the SH3 domain of MAP3K10. This protein interaction domain has been shown to play a role in the auto-regulation of MAP3K10. SH3-defective mutants of the closely related protein MLK3 exhibited increased catalytic activity compared with wild type MLK3 suggesting that the SH3 domain negatively regulates MLK3 activity by interacting with the Cdc42/Rac binding motif in the C-terminus of mixed linage kinases.
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