Редактирование: HERC1 (раздел)

==Publications==

{{medline-entry
|title=Progressive Purkinje cell degeneration in tambaleante mutant mice is a consequence of a missense mutation in [[HERC1]] E3 ubiquitin ligase.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20041218
|abstract=The HERC gene family encodes proteins with two characteristic domains: HECT and [[RCC1]]-like. Proteins with HECT domains have been described to function as ubiquitin ligases, and those that contain [[RCC1]]-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large ([[HERC1]]-2) and small (HERC3-6). The giant [[HERC1]] protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and [[TSC2]] proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a G<-->A transition at position 1448, causing a Gly to Glu substitution (Gly483Glu) in the highly conserved N-terminal [[RCC1]]-like domain of the [[HERC1]] protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human [[HERC1]] cDNA, validated our findings. Histological and biochemical studies revealed extensive autophagy associated with an increase of the mutant protein level and a decrease of mTOR activity. Our observations concerning this first mutation in the Herc1 gene contribute to the functional annotation of the encoded E3 ubiquitin ligase and underline the crucial and unexpected role of this protein in Purkinje cell physiology.
|mesh-terms=* Amino Acid Sequence
* Animals
* Base Sequence
* Chromosome Mapping
* Dendrites
* Gene Expression Regulation
* Genetic Loci
* Genotype
* Longevity
* Mice
* Mice, Neurologic Mutants
* Molecular Sequence Data
* Mutation, Missense
* Phenotype
* Purkinje Cells
* Ubiquitin-Protein Ligases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791161
}}