ID MYLIP_HUMAN Reviewed; 445 AA. AC Q8WY64; Q5TIA4; Q9BU73; Q9NRL9; Q9UHE7; DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2005, sequence version 2. DT 27-MAR-2024, entry version 188. DE RecName: Full=E3 ubiquitin-protein ligase MYLIP; DE EC=2.3.2.27; DE AltName: Full=Inducible degrader of the LDL-receptor; DE Short=Idol; DE AltName: Full=Myosin regulatory light chain interacting protein; DE Short=MIR; DE AltName: Full=RING-type E3 ubiquitin transferase MYLIP {ECO:0000305}; GN Name=MYLIP; Synonyms=BZF1, IDOL; ORFNames=BM-023, PP5242; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL RP STAGE, FUNCTION, INTERACTION WITH MYOSIN REGULATORY LIGHT CHAIN (MRLC), AND RP VARIANT SER-342. RC TISSUE=Brain; RX PubMed=10593918; DOI=10.1074/jbc.274.51.36288; RA Olsson P.-A., Korhonen L., Mercer E.A., Lindholm D.; RT "MIR is a novel ERM-like protein that interacts with myosin regulatory RT light chain and inhibits neurite outgrowth."; RL J. Biol. Chem. 274:36288-36292(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-342. RA Shi W., Mullersman J.E.; RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT SER-342. RC TISSUE=Bone marrow; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-342. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP MUTAGENESIS OF CYS-387, FUNCTION, SUBCELLULAR LOCATION, AND RP AUTOUBIQUITINATION. RX PubMed=14550572; DOI=10.1016/s0014-5793(03)01010-x; RA Bornhauser B.C., Johansson C., Lindholm D.; RT "Functional activities and cellular localization of the ezrin, radixin, RT moesin (ERM) and RING zinc finger domains in MIR."; RL FEBS Lett. 553:195-199(2003). RN [10] RP FUNCTION, AND INTERACTION WITH TMEM4. RX PubMed=12826659; DOI=10.1074/jbc.m306271200; RA Bornhauser B.C., Olsson P.-A., Lindholm D.; RT "MSAP is a novel MIR-interacting protein that enhances neurite outgrowth RT and increases myosin regulatory light chain."; RL J. Biol. Chem. 278:35412-35420(2003). RN [11] RP FUNCTION, INDUCTION, AND MUTAGENESIS OF CYS-387. RX PubMed=19520913; DOI=10.1126/science.1168974; RA Zelcer N., Hong C., Boyadjian R., Tontonoz P.; RT "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of RT the LDL receptor."; RL Science 325:100-104(2009). RN [12] RP FUNCTION. RX PubMed=20427281; DOI=10.1074/jbc.m110.123729; RA Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V., RA Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J., RA van Berkel T.J., Tontonoz P., Zelcer N.; RT "The E3 ubiquitin ligase IDOL induces the degradation of the low density RT lipoprotein receptor family members VLDLR and ApoER2."; RL J. Biol. Chem. 285:19720-19726(2010). RN [13] RP FUNCTION, AUTOUBIQUITINATION, AND MUTAGENESIS OF TYR-265 AND THR-269. RX PubMed=22109552; DOI=10.1073/pnas.1111589108; RA Calkin A.C., Goult B.T., Zhang L., Fairall L., Hong C., Schwabe J.W., RA Tontonoz P.; RT "FERM-dependent E3 ligase recognition is a conserved mechanism for targeted RT degradation of lipoprotein receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 108:20107-20112(2011). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 369-445 IN COMPLEX WITH UBE2D1, RP SUBUNIT, ACTIVITY REGULATION, IRON-BINDING SITES, AND MUTAGENESIS OF RP CYS-387; VAL-389 AND LEU-415. RX PubMed=21685362; DOI=10.1101/gad.2056211; RA Zhang L., Fairall L., Goult B.T., Calkin A.C., Hong C., Millard C.J., RA Tontonoz P., Schwabe J.W.; RT "The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL RT receptor."; RL Genes Dev. 25:1262-1274(2011). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and CC subsequent proteasomal degradation of myosin regulatory light chain CC (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the CC UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite CC outgrowth in presence of NGF by counteracting the stabilization of MRLC CC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated CC neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular CC cholesterol uptake by mediating ubiquitination and subsequent CC degradation of LDLR. {ECO:0000269|PubMed:10593918, CC ECO:0000269|PubMed:12826659, ECO:0000269|PubMed:14550572, CC ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:20427281, CC ECO:0000269|PubMed:22109552}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; CC -!- ACTIVITY REGULATION: Can bind 1 iron ion per dimer. Iron binding seems CC to decrease LDLR degradation activity. {ECO:0000269|PubMed:21685362}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, CC UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory CC light chain (MRLC) and TMEM4. {ECO:0000269|PubMed:10593918, CC ECO:0000269|PubMed:12826659, ECO:0000269|PubMed:21685362}. CC -!- INTERACTION: CC Q8WY64; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-6952711, EBI-10173507; CC Q8WY64; Q92870-2: APBB2; NbExp=3; IntAct=EBI-6952711, EBI-21535880; CC Q8WY64; Q03989: ARID5A; NbExp=3; IntAct=EBI-6952711, EBI-948603; CC Q8WY64; P54252: ATXN3; NbExp=3; IntAct=EBI-6952711, EBI-946046; CC Q8WY64; Q9Y2B0: CNPY2; NbExp=3; IntAct=EBI-6952711, EBI-1054195; CC Q8WY64; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-6952711, EBI-742054; CC Q8WY64; G5E9A7: DMWD; NbExp=3; IntAct=EBI-6952711, EBI-10976677; CC Q8WY64; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-6952711, EBI-2349927; CC Q8WY64; Q9NQT4: EXOSC5; NbExp=3; IntAct=EBI-6952711, EBI-371876; CC Q8WY64; Q9NTX9: FAM217B; NbExp=3; IntAct=EBI-6952711, EBI-19153639; CC Q8WY64; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-6952711, EBI-2548508; CC Q8WY64; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-6952711, EBI-10961706; CC Q8WY64; O43464: HTRA2; NbExp=3; IntAct=EBI-6952711, EBI-517086; CC Q8WY64; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-6952711, EBI-6398041; CC Q8WY64; Q9C086: INO80B; NbExp=3; IntAct=EBI-6952711, EBI-715611; CC Q8WY64; Q5T7N3: KANK4; NbExp=3; IntAct=EBI-6952711, EBI-9355810; CC Q8WY64; O14901: KLF11; NbExp=3; IntAct=EBI-6952711, EBI-948266; CC Q8WY64; Q8N448: LNX2; NbExp=4; IntAct=EBI-6952711, EBI-2340947; CC Q8WY64; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-6952711, EBI-2548751; CC Q8WY64; P0CG21: NHLRC4; NbExp=3; IntAct=EBI-6952711, EBI-12868744; CC Q8WY64; Q86UR1-2: NOXA1; NbExp=5; IntAct=EBI-6952711, EBI-12025760; CC Q8WY64; Q6NSM0: NR1D2; NbExp=6; IntAct=EBI-6952711, EBI-10250949; CC Q8WY64; P55771: PAX9; NbExp=6; IntAct=EBI-6952711, EBI-12111000; CC Q8WY64; D3DTS7: PMP22; NbExp=3; IntAct=EBI-6952711, EBI-25882629; CC Q8WY64; Q8WWW0: RASSF5; NbExp=4; IntAct=EBI-6952711, EBI-367390; CC Q8WY64; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-6952711, EBI-748391; CC Q8WY64; O00560: SDCBP; NbExp=3; IntAct=EBI-6952711, EBI-727004; CC Q8WY64; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-6952711, EBI-5235340; CC Q8WY64; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-6952711, EBI-11955057; CC Q8WY64; Q86WV8: TSC1; NbExp=6; IntAct=EBI-6952711, EBI-12806590; CC Q8WY64; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-6952711, EBI-739485; CC Q8WY64; Q05516: ZBTB16; NbExp=3; IntAct=EBI-6952711, EBI-711925; CC Q8WY64; Q99592: ZBTB18; NbExp=3; IntAct=EBI-6952711, EBI-3232046; CC Q8WY64; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-6952711, EBI-12287587; CC Q8WY64; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-6952711, EBI-740727; CC Q8WY64; Q7Z4V0: ZNF438; NbExp=3; IntAct=EBI-6952711, EBI-11962468; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:14550572}. Cell CC membrane {ECO:0000269|PubMed:14550572}; Peripheral membrane protein CC {ECO:0000269|PubMed:14550572}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8WY64-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WY64-2; Sequence=VSP_011828, VSP_011829; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:10593918}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal tissues and higher levels were CC detected in placenta and fetal lung. {ECO:0000269|PubMed:10593918}. CC -!- INDUCTION: Expression is directly activated by NR1H2 and NR1H3. CC Expression is not dependent of the sterol-response element-binding CC proteins (SREBPs). Expression is indirectly induced by LDL. CC {ECO:0000269|PubMed:19520913}. CC -!- DOMAIN: The RING domain mediates ubiquitination and the neurite CC outgrowth inhibitory activity. CC -!- DOMAIN: The FERM domain binds phospholipids and mediates lipoprotein CC receptors recognition at the plasma membrane through their cytoplasmic CC tails. CC -!- DOMAIN: The RING-type zinc finger mediates the interaction with UBE2D CC E2 enzymes. CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:14550572, CC ECO:0000269|PubMed:22109552}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF187016; AAF18974.1; -; mRNA. DR EMBL; AF006003; AAQ13408.1; -; mRNA. DR EMBL; AF006004; AAQ13409.1; -; Genomic_DNA. DR EMBL; AF212221; AAF87323.1; -; mRNA. DR EMBL; AF258586; AAG23789.1; -; mRNA. DR EMBL; BT007055; AAP35704.1; -; mRNA. DR EMBL; AL021407; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471087; EAW55366.1; -; Genomic_DNA. DR EMBL; BC002860; AAH02860.1; -; mRNA. DR CCDS; CCDS4536.1; -. [Q8WY64-1] DR RefSeq; NP_037394.2; NM_013262.3. [Q8WY64-1] DR PDB; 2YHN; X-ray; 3.00 A; A/B=369-445. DR PDB; 2YHO; X-ray; 2.10 A; A/C/E/G=369-445. DR PDB; 6QLY; X-ray; 2.50 A; A=1-344. DR PDB; 6QLZ; X-ray; 2.34 A; A/B/C=183-283. DR PDBsum; 2YHN; -. DR PDBsum; 2YHO; -. DR PDBsum; 6QLY; -. DR PDBsum; 6QLZ; -. DR AlphaFoldDB; Q8WY64; -. DR BMRB; Q8WY64; -. DR SMR; Q8WY64; -. DR BioGRID; 118882; 55. DR IntAct; Q8WY64; 45. DR MINT; Q8WY64; -. DR STRING; 9606.ENSP00000349298; -. DR iPTMnet; Q8WY64; -. DR PhosphoSitePlus; Q8WY64; -. DR BioMuta; MYLIP; -. DR DMDM; 84028296; -. DR jPOST; Q8WY64; -. DR MassIVE; Q8WY64; -. DR PaxDb; 9606-ENSP00000349298; -. DR PeptideAtlas; Q8WY64; -. DR ProteomicsDB; 75131; -. [Q8WY64-1] DR Antibodypedia; 25043; 271 antibodies from 28 providers. DR DNASU; 29116; -. DR Ensembl; ENST00000356840.8; ENSP00000349298.3; ENSG00000007944.15. [Q8WY64-1] DR GeneID; 29116; -. DR KEGG; hsa:29116; -. DR MANE-Select; ENST00000356840.8; ENSP00000349298.3; NM_013262.4; NP_037394.2. DR UCSC; uc003nbq.4; human. [Q8WY64-1] DR AGR; HGNC:21155; -. DR DisGeNET; 29116; -. DR GeneCards; MYLIP; -. DR HGNC; HGNC:21155; MYLIP. DR HPA; ENSG00000007944; Low tissue specificity. DR MIM; 610082; gene. DR neXtProt; NX_Q8WY64; -. DR OpenTargets; ENSG00000007944; -. DR Orphanet; 426; NON RARE IN EUROPE: Familial hypobetalipoproteinemia. DR PharmGKB; PA134942677; -. DR VEuPathDB; HostDB:ENSG00000007944; -. DR eggNOG; ENOG502QV76; Eukaryota. DR GeneTree; ENSGT00940000156206; -. DR HOGENOM; CLU_031820_1_0_1; -. DR InParanoid; Q8WY64; -. DR OMA; FYCCETV; -. DR OrthoDB; 5406876at2759; -. DR PhylomeDB; Q8WY64; -. DR TreeFam; TF351936; -. DR PathwayCommons; Q8WY64; -. DR Reactome; R-HSA-8866427; VLDLR internalisation and degradation. DR Reactome; R-HSA-9031525; NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8WY64; -. DR SIGNOR; Q8WY64; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 29116; 60 hits in 1206 CRISPR screens. DR ChiTaRS; MYLIP; human. DR GeneWiki; MYLIP; -. DR GenomeRNAi; 29116; -. DR Pharos; Q8WY64; Tbio. DR PRO; PR:Q8WY64; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q8WY64; Protein. DR Bgee; ENSG00000007944; Expressed in oocyte and 201 other cell types or tissues. DR ExpressionAtlas; Q8WY64; baseline and differential. DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl. DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Ensembl. DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:UniProtKB. DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl. DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0032803; P:regulation of low-density lipoprotein particle receptor catabolic process; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13195; FERM_C_MYLIP_IDOL; 1. DR CDD; cd17104; FERM_F1_MYLIP; 1. DR CDD; cd16523; RING-HC_MYLIP; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR000798; Ez/rad/moesin-like. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR018979; FERM_N. DR InterPro; IPR018980; FERM_PH-like_C. DR InterPro; IPR041790; MYLIP_FERM_C. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR23280; 4.1 G PROTEIN; 1. DR PANTHER; PTHR23280:SF13; E3 UBIQUITIN-PROTEIN LIGASE MYLIP; 1. DR Pfam; PF09380; FERM_C; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF09379; FERM_N; 1. DR Pfam; PF13920; zf-C3HC4_3; 1. DR PRINTS; PR00935; BAND41. DR PRINTS; PR00661; ERMFAMILY. DR SMART; SM00295; B41; 1. DR SMART; SM01196; FERM_C; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q8WY64; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Iron; KW Membrane; Metal-binding; Reference proteome; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..445 FT /note="E3 ubiquitin-protein ligase MYLIP" FT /id="PRO_0000055972" FT DOMAIN 1..279 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT ZN_FING 387..422 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 431..433 FT /note="Critical for homodimerization" FT BINDING 360 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT BINDING 363 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT BINDING 368 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT VAR_SEQ 1..181 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11042152" FT /id="VSP_011828" FT VAR_SEQ 316..445 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11042152" FT /id="VSP_011829" FT VARIANT 342 FT /note="N -> S (in dbSNP:rs9370867)" FT /evidence="ECO:0000269|PubMed:10593918, FT ECO:0000269|PubMed:11042152, ECO:0000269|PubMed:15498874, FT ECO:0000269|Ref.2" FT /id="VAR_019805" FT MUTAGEN 265 FT /note="Y->A: Unable to clear LDLR from the plasma FT membrane." FT /evidence="ECO:0000269|PubMed:22109552" FT MUTAGEN 269 FT /note="T->R: Unable to clear LDLR from the plasma FT membrane." FT /evidence="ECO:0000269|PubMed:22109552" FT MUTAGEN 387 FT /note="C->A: Abolishes autoubiquitination." FT /evidence="ECO:0000269|PubMed:14550572, FT ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:21685362" FT MUTAGEN 387 FT /note="C->A: Abolishes ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:14550572, FT ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:21685362" FT MUTAGEN 389 FT /note="V->R: Inhibits LDLR degradation." FT /evidence="ECO:0000269|PubMed:21685362" FT MUTAGEN 415 FT /note="L->E: Inhibits LDLR degradation." FT /evidence="ECO:0000269|PubMed:21685362" FT CONFLICT 199 FT /note="K -> R (in Ref. 1; AAF18974)" FT /evidence="ECO:0000305" FT CONFLICT 262..263 FT /note="SG -> TR (in Ref. 3; AAF87323)" FT /evidence="ECO:0000305" FT CONFLICT 309..310 FT /note="KK -> PRN (in Ref. 3; AAF87323)" FT /evidence="ECO:0000305" FT STRAND 2..6 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 12..16 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 23..34 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 39..41 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 42..47 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 62..65 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 71..80 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 84..86 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 90..105 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 113..127 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:6QLY" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 150..162 FT /evidence="ECO:0007829|PDB:6QLY" FT TURN 163..165 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 168..181 FT /evidence="ECO:0007829|PDB:6QLY" FT TURN 183..186 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 188..193 FT /evidence="ECO:0007829|PDB:6QLZ" FT TURN 195..197 FT /evidence="ECO:0007829|PDB:6QLY" FT STRAND 199..204 FT /evidence="ECO:0007829|PDB:6QLZ" FT STRAND 206..213 FT /evidence="ECO:0007829|PDB:6QLZ" FT STRAND 218..223 FT /evidence="ECO:0007829|PDB:6QLZ" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:6QLZ" FT STRAND 227..233 FT /evidence="ECO:0007829|PDB:6QLZ" FT STRAND 236..242 FT /evidence="ECO:0007829|PDB:6QLZ" FT STRAND 248..254 FT /evidence="ECO:0007829|PDB:6QLZ" FT HELIX 258..270 FT /evidence="ECO:0007829|PDB:6QLZ" FT TURN 273..275 FT /evidence="ECO:0007829|PDB:6QLZ" FT HELIX 280..298 FT /evidence="ECO:0007829|PDB:6QLY" FT TURN 308..310 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 319..331 FT /evidence="ECO:0007829|PDB:6QLY" FT HELIX 374..384 FT /evidence="ECO:0007829|PDB:2YHO" FT TURN 388..390 FT /evidence="ECO:0007829|PDB:2YHO" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:2YHO" FT STRAND 397..400 FT /evidence="ECO:0007829|PDB:2YHO" FT HELIX 409..412 FT /evidence="ECO:0007829|PDB:2YHO" FT TURN 419..421 FT /evidence="ECO:0007829|PDB:2YHO" FT STRAND 427..430 FT /evidence="ECO:0007829|PDB:2YHO" SQ SEQUENCE 445 AA; 49910 MW; 342E643B0532B45C CRC64; MLCYVTRPDA VLMEVEVEAK ANGEDCLNQV CRRLGIIEVD YFGLQFTGSK GESLWLNLRN RISQQMDGLA PYRLKLRVKF FVEPHLILQE QTRHIFFLHI KEALLAGHLL CSPEQAVELS ALLAQTKFGD YNQNTAKYNY EELCAKELSS ATLNSIVAKH KELEGTSQAS AEYQVLQIVS AMENYGIEWH SVRDSEGQKL LIGVGPEGIS ICKDDFSPIN RIAYPVVQMA TQSGKNVYLT VTKESGNSIV LLFKMISTRA ASGLYRAITE THAFYRCDTV TSAVMMQYSR DLKGHLASLF LNENINLGKK YVFDIKRTSK EVYDHARRAL YNAGVVDLVS RNNQSPSHSP LKSSESSMNC SSCEGLSCQQ TRVLQEKLRK LKEAMLCMVC CEEEINSTFC PCGHTVCCES CAAQLQSCPV CRSRVEHVQH VYLPTHTSLL NLTVI //