| Tbio | E3 ubiquitin-protein ligase MYLIP |
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.
The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]
The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count |
|---|---|
| Endometriosis | 535 |
| Disease | Target Count | P-value |
|---|---|---|
| atypical teratoid/rhabdoid tumor | 1095 | 1.59827713903704E-8 |
| lung adenocarcinoma | 2714 | 2.67536274026712E-6 |
| malignant mesothelioma | 3163 | 7.85707199070718E-6 |
| osteosarcoma | 7933 | 4.55308187795423E-5 |
| tuberculosis and treatment for 6 months | 686 | 1.58186348424119E-4 |
| ulcerative colitis | 2087 | 1.71310264427134E-4 |
| group 4 medulloblastoma | 1875 | 2.50861146161733E-4 |
| adult high grade glioma | 2148 | 0.0031051129512065 |
| acute myeloid leukemia | 785 | 0.00541983549842801 |
| ovarian cancer | 8492 | 0.00942697704347509 |
| pancreatic carcinoma | 567 | 0.0101432680083894 |
| pancreatic cancer | 2300 | 0.0101432680083896 |
| adrenocortical carcinoma | 1427 | 0.0239521825319872 |
| medulloblastoma, large-cell | 6234 | 0.026190020710391 |
| Disease | log2 FC | p |
|---|---|---|
| pancreatic cancer | -1.200 | 0.010 |
| malignant mesothelioma | 1.500 | 0.000 |
| osteosarcoma | 1.939 | 0.000 |
| group 4 medulloblastoma | -1.800 | 0.000 |
| atypical teratoid/rhabdoid tumor | -1.700 | 0.000 |
| medulloblastoma, large-cell | -1.300 | 0.026 |
| adrenocortical carcinoma | -1.166 | 0.024 |
| tuberculosis and treatment for 6 months | 1.100 | 0.000 |
| adult high grade glioma | -1.100 | 0.003 |
| pancreatic carcinoma | -1.200 | 0.010 |
| lung adenocarcinoma | -1.200 | 0.000 |
| acute myeloid leukemia | 1.200 | 0.005 |
| ulcerative colitis | -1.100 | 0.000 |
| ovarian cancer | 1.200 | 0.009 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Horse | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Chicken | OMA EggNOG Inparanoid |
| Anole lizard | OMA EggNOG Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| Zebrafish | OMA EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 26719329 | Data suggest inducible expression of IDOL is subject to robust, rapid regulation by process that is sensitive to deubiquitinase inhibition in human/mouse cell lines and primary human cells; transcriptional induction of IDOL leads to degradation of LDLR. |
| 26666640 | Identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. |
| 26601593 | Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients |
| 26527619 | The study identified MARCH6 as a negative regulator of SREBP2-mediated transcription and described an unexpected E3 circuit functionally linking MARCH6 and IDOL to limit uptake of low-density lipoprotein via the LDLR pathway. |
| 25927920 | IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population. |
| 25171759 | study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. |
| 24935961 | Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions in transgenic mice. |
| 23733886 | evidence for the existence of an LXR-IDOL-mediated internalization pathway for the LDLR that is distinct from that used for lipoprotein uptake |
| 23382078 | IDOL is recruited to plasma membrane by low-density lipoprotein receptor (LDLR), promotes LDLR internalization in the absence of clathrin or caveolae, and facilitates LDLR degradation by shuttling it into the multivesicular body protein-sorting pathway |
| 23324548 | Results show that IDOL contributes to variation in circulating levels of LDL-C. |
| More... |
MLCYVTRPDAVLMEVEVEAKANGEDCLNQVCRRLGIIEVDYFGLQFTGSKGESLWLNLRNRISQQMDGLA 1 - 70 PYRLKLRVKFFVEPHLILQEQTRHIFFLHIKEALLAGHLLCSPEQAVELSALLAQTKFGDYNQNTAKYNY 71 - 140 EELCAKELSSATLNSIVAKHKELEGTSQASAEYQVLQIVSAMENYGIEWHSVRDSEGQKLLIGVGPEGIS 141 - 210 ICKDDFSPINRIAYPVVQMATQSGKNVYLTVTKESGNSIVLLFKMISTRAASGLYRAITETHAFYRCDTV 211 - 280 TSAVMMQYSRDLKGHLASLFLNENINLGKKYVFDIKRTSKEVYDHARRALYNAGVVDLVSRNNQSPSHSP 281 - 350 LKSSESSMNCSSCEGLSCQQTRVLQEKLRKLKEAMLCMVCCEEEINSTFCPCGHTVCCESCAAQLQSCPV 351 - 420 CRSRVEHVQHVYLPTHTSLLNLTVI 421 - 445 //
| PMID | Year | Title |
|---|---|---|
| 26719329 | 2016 | Deubiquitylase Inhibition Reveals Liver X Receptor-independent Transcriptional Regulation of the E3 Ubiquitin Ligase IDOL and Lipoprotein Uptake. |
| 26666640 | 2016 | The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. |
| 26601593 | 2016 | IDOL, inducible degrader of low-density lipoprotein receptor, serves as a potential therapeutic target for dyslipidemia. |
| 26527619 | 2015 | A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes. |
| 25927920 | 2015 | IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population. |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. |
| 25171759 | 2014 | The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia. |
| 24935961 | 2014 | Transgenic expression of dominant-active IDOL in liver causes diet-induced hypercholesterolemia and atherosclerosis in mice. |
| 24097068 | 2013 | Discovery and refinement of loci associated with lipid levels. |
| 23733886 | 2013 | The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation. |
| More... |
