MYLIP_MOUSE
ID MYLIP_MOUSE Reviewed; 445 AA.
AC Q8BM54; Q3TX01; Q8BLY9; Q91Z47;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 162.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=14651927; DOI=10.1016/j.ydbio.2003.09.001;
RA Knowlton M.N., Chan B.M.C., Kelly G.M.;
RT "The zebrafish band 4.1 member Mir is involved in cell movements associated
RT with gastrulation.";
RL Dev. Biol. 264:407-429(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Aorta, Embryo, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-387, AND UBIQUITINATION.
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 [5]
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).
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:19520913,
CC ECO:0000269|PubMed:20427281}.
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:0000250|UniProtKB:Q8WY64}.
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:0000250|UniProtKB:Q8WY64}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8WY64}; Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BM54-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BM54-2; Sequence=VSP_011830;
CC -!- TISSUE SPECIFICITY: Expressed in liver, spleen, intestine and adrenals.
CC {ECO:0000269|PubMed:19520913}.
CC -!- DOMAIN: The RING domain mediates ubiquitination and the neurite
CC outgrowth inhibitory activity. {ECO:0000250}.
CC -!- DOMAIN: The FERM domain binds phospholipids and mediates lipoprotein
CC receptors recognition at the plasma membrane through their cytoplasmic
CC tails. {ECO:0000250}.
CC -!- DOMAIN: The RING-type zinc finger mediates the interaction with UBE2D
CC E2 enzymes. {ECO:0000250}.
CC -!- PTM: Autoubiquitinated. {ECO:0000305|PubMed:19520913}.
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; AY434449; AAQ98867.1; -; mRNA.
DR EMBL; AK034887; BAC28868.1; -; mRNA.
DR EMBL; AK040836; BAC30716.1; -; mRNA.
DR EMBL; AK159478; BAE35115.1; -; mRNA.
DR EMBL; BC010206; AAH10206.1; -; mRNA.
DR CCDS; CCDS36648.1; -. [Q8BM54-1]
DR RefSeq; NP_722484.2; NM_153789.3. [Q8BM54-1]
DR AlphaFoldDB; Q8BM54; -.
DR BMRB; Q8BM54; -.
DR SMR; Q8BM54; -.
DR BioGRID; 229999; 4.
DR IntAct; Q8BM54; 1.
DR MINT; Q8BM54; -.
DR STRING; 10090.ENSMUSP00000047403; -.
DR PhosphoSitePlus; Q8BM54; -.
DR PaxDb; Q8BM54; -.
DR PRIDE; Q8BM54; -.
DR ProteomicsDB; 287570; -. [Q8BM54-1]
DR ProteomicsDB; 287571; -. [Q8BM54-2]
DR Antibodypedia; 25043; 236 antibodies from 28 providers.
DR DNASU; 218203; -.
DR Ensembl; ENSMUST00000038275; ENSMUSP00000047403; ENSMUSG00000038175. [Q8BM54-1]
DR Ensembl; ENSMUST00000222178; ENSMUSP00000152597; ENSMUSG00000038175. [Q8BM54-2]
DR GeneID; 218203; -.
DR KEGG; mmu:218203; -.
DR UCSC; uc007qgz.1; mouse. [Q8BM54-1]
DR CTD; 29116; -.
DR MGI; MGI:2388271; Mylip.
DR VEuPathDB; HostDB:ENSMUSG00000038175; -.
DR eggNOG; ENOG502QV76; Eukaryota.
DR GeneTree; ENSGT00940000156206; -.
DR HOGENOM; CLU_031820_1_0_1; -.
DR InParanoid; Q8BM54; -.
DR OMA; CRALNII; -.
DR OrthoDB; 1340284at2759; -.
DR PhylomeDB; Q8BM54; -.
DR TreeFam; TF351936; -.
DR Reactome; R-MMU-8866427; VLDLR internalisation and degradation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 218203; 7 hits in 77 CRISPR screens.
DR ChiTaRS; Mylip; mouse.
DR PRO; PR:Q8BM54; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8BM54; protein.
DR Bgee; ENSMUSG00000038175; Expressed in prostate gland ventral lobe and 252 other tissues.
DR Genevisible; Q8BM54; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IC:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IDA:BHF-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; ISO:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0031648; P:protein destabilization; IDA:BHF-UCL.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:0032803; P:regulation of low-density lipoprotein particle receptor catabolic process; IMP:BHF-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
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 Alternative splicing; Cell membrane; Cytoplasm; Iron; Membrane;
KW 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_0000055973"
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 340..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..433
FT /note="Critical for homodimerization"
FT /evidence="ECO:0000250"
FT BINDING 360
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 363
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 368
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011830"
FT MUTAGEN 387
FT /note="C->A: Loss of ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:19520913"
FT CONFLICT 113
FT /note="P -> A (in Ref. 3; AAH10206)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 49849 MW; 31C73572C95D0711 CRC64;
MLCYVTRPDA VLMEVEVEAK ANGEDCLNQV CRRLGIIEVD YFGLQFTGSK GESLWLNLRN
RISQQMDGLA PYRLKLRVKF FVEPHLILQE QTRHIFFLHI KESLLAGHLQ CSPEQAVELS
ALLAQTKFGD YNQNTAQYSY EDLCEKELSS STLNSIVAKH KELEGISQAS AEYQVLQIVS
AMENYGIEWH AVRDSEGQKL LIGVGPEGIS ICKEDFSPIN RIAYPVVQMA TQSGKNVYLT
VTKESGNSIV LLFKMISTRA ASGLYRAITE THAFYRCDTV TSAVMMQYSR DLKGHLASLF
LNENINLGKK YVFDIKRTSK EVYDHARRAL YNAGVVDLVS RSDQSPPSSP LKSSDSSMSC
SSCEGLSCQQ TRVLQEKLRK LKEAMLCMAC CEEEINSTFC PCGHTVCCES CAAQLQSCPV
CRSRVEHVQH VYLPTHTSLL NLTVI
