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metabolism
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the ubiquitin ligase Huwe1 operates upstream of the N-Myc-DLL3-Notch pathway to control neural stem cell activity and promote neurogenesis, it is part of the Huwe1-N-myc pathway
malfunction
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Huwe1 balances proliferation and neurogenesis in the developing brain which is subverted in malignant brain tumors
malfunction
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mahogunin ring finger-1, MGRN1, is a RING domain-containing ubiquitin ligase mutated in mahoganoid, a mouse mutation causing coat color darkening, congenital heart defects, high embryonic lethality, and spongiform neurodegeneration. MGRN1 isoforms decrease MC1R and MC4R signaling to cAMP, without effect on beta2-adrenergic receptor and independently on receptor plasma membrane expression, ubiquitylation, internalization, or stability and occurred upstream of Galphas binding to/activation of adenylyl cyclase. Overexpression of Galpha5 abolishes the inhibitory effect of MGRN1
malfunction
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mice with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal hyperalgesia. Loss of MYCBP2 constitutively activates p38 MAPK and increases expression of several proteins involved in receptor trafficking. Loss of MYCBP2 inhibits internalization of transient receptor potential vanilloid receptor 1 and prevents desensitization of capsaicin-induced calcium increases
malfunction
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selective genetic inactivation of Cbl-b E3 ligase activity (C373AKI/KI knock-in) phenocopies the T cell responses observed when total Cbl-b is ablated, resulting in T cell hyperactivation, spontaneous autoimmunity, and impaired induction of T cell anergy in vivo. Mice carrying a Cbl-b E3 ligase-defective mutation spontaneously reject tumor cells that express human papilloma virus Ags
malfunction
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the knockdown of Fbxo45 in primary cultured hippocampal neurons results in a greater frequency of miniature excitatory postsynaptic currents
physiological function
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E3 ubiquitin ligases target specific molecules for proteolytic destruction and are key regulators of immune functions. The HECT-type E3 ligase AIP2 positively regulates T-cell activation, and AIP2 regulates activation-induced T-cell death by suppressing EGR2-mediated FasL expression via the ubiquitin pathway
physiological function
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E6-AP, a HECT domain family ubiquitin ligase implicated in Angelman syndrome, interacts with the substrate binding domain of Hsp70/Hsc70 chaperones and promotes the degradation of chaperone bound substrates
physiological function
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MGRN-1 is one of two accessory proteins for MC signaling, it inhibits functional coupling of MC1R and MC4R to the cAMP pathway, overview
physiological function
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the ubiquitin ligase Huwe1 operates upstream of the N-Myc-DLL3-Notch pathway to control neural stem cell activity and promote neurogenesis. It acts as tumor suppressor gene
physiological function
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Fbxo45 regulates neurotransmission at mature neurons. Fbxo45 induces the degradation of the synaptic vesicle-priming factor Munc13-1. Fbxo45 plays an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse
physiological function
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MYCBP2 regulates internalization of transient receptor potential vanilloid receptor 1 in peripheral sensory neurons as well as duration of thermal hyperalgesia through p38 MAPK. MYCBP2 negatively controls neuronal growth
physiological function
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the catalytic function of the E3 ligase Cbl-b is essential for negative regulation of T cells in vivo. Cbl-b E3 ligase activity is required for in vivo T cell tolerance
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