MYLIP_HUMAN
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 03-AUG-2022, entry version 180.
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}.
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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; 44.
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; Q8WY64; -.
DR PeptideAtlas; Q8WY64; -.
DR PRIDE; Q8WY64; -.
DR ProteomicsDB; 75131; -. [Q8WY64-1]
DR Antibodypedia; 25043; 236 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 CTD; 29116; -.
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; CRALNII; -.
DR OrthoDB; 1340284at2759; -.
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 UniPathway; UPA00143; -.
DR BioGRID-ORCS; 29116; 53 hits in 1119 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 199 other tissues.
DR ExpressionAtlas; Q8WY64; baseline and differential.
DR Genevisible; Q8WY64; HS.
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 Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 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 Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SMART; SM01196; FERM_C; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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
