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Enzyme Nomenclature
Information on EC 6.3.2.19 - ubiquitin-protein ligase
for references in articles please use BRENDA:EC6.3.2.19deleted. The ubiquitinylation process is now known to be performed by several enzymes in sequence, starting with EC 6.2.1.45 (ubiquitin-activating enzyme E1) and followed by several transfer reactions, including those of EC 2.3.2.23 (E2 ubiquitin-conjugating enzyme) and EC 2.3.2.27 (RING-type E3 ubiquitin transferase)
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EC Tree
6.3.2.19 ubiquitin-protein ligase
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
malfunction
metabolism
physiological function
malfunction
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elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx is involved in skeletal muscle protein breakdown in rats with thermal injury
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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ubiquitin ligases are associated with several diseases, e.g. cancer, neurodegeneration, viral infection, and metabolinc and immune diesases
malfunction
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downregulation of IBRDC2 induces increased cellular levels and accumulation of the active form of Bax
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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MURF3 knockdown in cardiomyocytes by an isogene-specific siRNA leads to upregulation of MURF2 expression. Knockdown of both MURF2 and MURF3 severely disrupts the formation of ordered Z- and M-bands, likely by perturbed tubulin dynamics. It is suggested that ubiquitin-mediated protein turnover and MURF2 in particular play an unrecognised role in the earliest steps of heart muscle differentiation, and that partial complementation of MURF2 deficiency is afforded by MURF3
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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silencing of Mule stabilizes Miz1, thereby suppressing TNFalpha-induced JNK activation and cell death
malfunction
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siRNA knockdown of MURF2 in neonatal rat cardiomyocytes disrupts posttranslational microtubule modification and myofibril assembly, and is only partly compensated by upregulation of MURF3 but not MURF1. It is suggested that ubiquitin-mediated protein turnover and MURF2 in particular play an unrecognised role in the earliest steps of heart muscle differentiation, and that partial complementation of MURF2 deficiency is afforded by MURF3
malfunction
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the knockdown of Fbxo45 in primary cultured hippocampal neurons results in a greater frequency of miniature excitatory postsynaptic currents
malfunction
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the knockdown of Fbxo45 in primary cultured hippocampal neurons results in a greater frequency of miniature excitatory postsynaptic currents
metabolism
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the enzyme is essential in the intercellular Notch signaling pathway, overview
metabolism
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the enzyme is involved in the ubiquitin-proteasome pathway, UPS, where it mediates the ubiquitin transfer from E2, the ubiquitin-conjugating enzyme to the lysine residue(s) of the substrate
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
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, mechanism, overview. All MGRN1 isozymes decrease agonist-induced cAMP production by as much as 50%
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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RMA E3 Ub ligases may play a role in the growth and development of Arabidopsis thaliana
physiological function
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subunit Fbw7 is considered to be a potent tumor suppressor
physiological function
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the CUL4ADDB1ROC1beta-TRCP complex is a major E3 ligase that regulates REDD1 stability
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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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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IBRDC2 is a regulatory factor for Bax and protects cells from unprompted Bax activation and cell death
physiological function
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MAPK kinase 4/SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase Itch. Itch controls MAPK kinase 4 stability
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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Smurf1 plays a critical role in embryogenesis and adult bone homeostasis
physiological function
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the BRCA1-BARD1 RING complex has an E3 ubiquitin ligase activity that plays an essential role in response to DNA damage
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
physiological function
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the E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain
physiological function
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the selective enrichment of Epe1 at boundaries requires its regulation by the conserved Cul4-Ddb1Cdt2 ubiquitin ligase, which directly recognizes Epe1 and promotes its polyubiquitylation and degradation. Epe1 is the sole target of the Cul4-Ddb1Cdt2 complex whose destruction is necessary for the preservation of heterochromatin
physiological function
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the ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid
physiological function
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UbcM2 regulates the stability and transcriptional activity of the antioxidant transcription factor Nrf2 (nuclear factor E2-related factor 2). UbcM2 is involved in the restoration of redox homeostasis following oxidative stress
physiological function
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Ube2 participates in fertilization or spermatogenesis/spermiogenesis
physiological function
-
ubiquitin ligase Mule is required for TNFalpha-induced JNK activation
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx
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Release 2023.1 (January 2023)
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