ID:MYLIP_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase MYLIP; EC=6.3.2.-; AltName: Full=Inducible degrader of the LDL-receptor; Short=Idol; AltName: Full=Myosin regulatory light chain interacting protein; Short=MIR; FUNCTION: 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. ENZYME REGULATION: Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory light chain (MRLC) and TMEM4. SUBCELLULAR LOCATION: Cytoplasm (Probable). Cell membrane; Peripheral membrane protein. TISSUE SPECIFICITY: Ubiquitously expressed. DEVELOPMENTAL STAGE: Expressed in fetal tissues and higher levels were detected in placenta and fetal lung. INDUCTION: Expression is directly activated by NR1H2 and NR1H3. Expression is not dependent of the sterol-response element-binding proteins (SREBPs). Expression is indirectly induced by LDL. DOMAIN: The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity. DOMAIN: The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails. DOMAIN: The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes. PTM: Autoubiquitinated. SIMILARITY: Contains 1 FERM domain. SIMILARITY: Contains 1 RING-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q8WY64
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0008092 cytoskeletal protein binding GO:0016740 transferase activity GO:0046872 metal ion binding GO:0061630 ubiquitin protein ligase activity GO:0005200 structural constituent of cytoskeleton
Biological Process: GO:0000209 protein polyubiquitination GO:0006511 ubiquitin-dependent protein catabolic process GO:0007399 nervous system development GO:0010977 negative regulation of neuron projection development GO:0010989 negative regulation of low-density lipoprotein particle clearance GO:0016567 protein ubiquitination GO:0031648 protein destabilization GO:0032802 low-density lipoprotein particle receptor catabolic process GO:0032803 regulation of low-density lipoprotein particle receptor catabolic process GO:0042632 cholesterol homeostasis GO:0045732 positive regulation of protein catabolic process GO:0031032 actomyosin structure organization
AK314648 - Homo sapiens cDNA, FLJ95492, highly similar to Homo sapiens myosin regulatory light chain interacting protein(MIR), mRNA. AK074391 - Homo sapiens cDNA FLJ23811 fis, clone HRC08372, highly similar to Homo sapiens myosin regulatory light chain interacting protein MIR mRNA. BC002860 - Homo sapiens myosin regulatory light chain interacting protein, mRNA (cDNA clone MGC:4180 IMAGE:3638617), complete cds. AF258586 - Homo sapiens PP5242 mRNA, complete cds. AF187016 - Homo sapiens myosin regulatory light chain interacting protein MIR mRNA, complete cds. AF006003 - Homo sapiens band 4.1 superfamily member BZF1 (BZF1) mRNA, complete cds. AF212221 - Homo sapiens BM023 mRNA, complete cds. JD535532 - Sequence 516556 from Patent EP1572962. JD406621 - Sequence 387645 from Patent EP1572962. EU176184 - Synthetic construct Homo sapiens clone IMAGE:100006342; FLH165473.01X; RZPDo839D03250D myosin regulatory light chain interacting protein (MYLIP) gene, encodes complete protein. CU678250 - Synthetic construct Homo sapiens gateway clone IMAGE:100019438 5' read MYLIP mRNA. HQ447323 - Synthetic construct Homo sapiens clone IMAGE:100070639; CCSB004200_03 myosin regulatory light chain interacting protein (MYLIP) gene, encodes complete protein. KJ893689 - Synthetic construct Homo sapiens clone ccsbBroadEn_03083 MYLIP gene, encodes complete protein. BT007055 - Homo sapiens myosin regulatory light chain interacting protein mRNA, complete cds. AK026739 - Homo sapiens cDNA: FLJ23086 fis, clone LNG06988, highly similar to AF187016 Homo sapiens myosin regulatory light chain interacting protein MIR mRNA. AJ420601 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1696899. LQ980393 - Sequence 39 from Patent WO2013050532. LQ980498 - Sequence 144 from Patent WO2013050532.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q8WY64 (Reactome details) participates in the following event(s):
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-8854628 MYLIP dimer ubiquitinates VLDLR on Lys-839 R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-8866427 VLDLR internalisation and degradation R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-8964043 Plasma lipoprotein clearance R-HSA-1280218 Adaptive Immune System R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance R-HSA-168256 Immune System R-HSA-382551 Transport of small molecules
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
