MYLIP_RAT
ID MYLIP_RAT Reviewed; 445 AA.
AC D3ZDI6;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 82.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP TISSUE SPECIFICITY.
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=11162443; DOI=10.1006/bbrc.2000.4028;
RA Olsson P.A., Bornhauser B.C., Korhonen L., Lindholm D.;
RT "Neuronal expression of the ERM-like protein MIR in rat brain and its
RT localization to human chromosome 6.";
RL Biochem. Biophys. Res. Commun. 279:879-883(2000).
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:0000250|UniProtKB:Q8BM54}.
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:0000250|UniProtKB:Q8WY64}. Cell
CC membrane {ECO:0000250|UniProtKB:Q8WY64}; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in developing and adult brain,
CC hippocampus, cerebellum, cerebral cortex, thalamus and substantia
CC nigra. Predominantly found in neurons. {ECO:0000269|PubMed:10593918,
CC ECO:0000269|PubMed:11162443}.
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. {ECO:0000250}.
CC -!- DOMAIN: The RING-type zinc finger mediates the interaction with UBE2D
CC E2 enzymes. {ECO:0000250}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250}.
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DR RefSeq; NP_001100814.2; NM_001107344.2.
DR AlphaFoldDB; D3ZDI6; -.
DR BMRB; D3ZDI6; -.
DR SMR; D3ZDI6; -.
DR STRING; 10116.ENSRNOP00000024021; -.
DR PaxDb; D3ZDI6; -.
DR Ensembl; ENSRNOT00000024021; ENSRNOP00000024021; ENSRNOG00000017579.
DR GeneID; 306825; -.
DR KEGG; rno:306825; -.
DR CTD; 29116; -.
DR RGD; 1305761; Mylip.
DR eggNOG; ENOG502QV76; Eukaryota.
DR GeneTree; ENSGT00940000156206; -.
DR HOGENOM; CLU_031820_1_0_1; -.
DR InParanoid; D3ZDI6; -.
DR OMA; CRALNII; -.
DR OrthoDB; 1340284at2759; -.
DR PhylomeDB; D3ZDI6; -.
DR TreeFam; TF351936; -.
DR Reactome; R-RNO-8866427; VLDLR internalisation and degradation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:D3ZDI6; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000017579; Expressed in thymus and 20 other tissues.
DR Genevisible; D3ZDI6; RN.
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:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; ISO:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
DR GO; GO:0032803; P:regulation of low-density lipoprotein particle receptor catabolic process; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:RGD.
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 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Iron; Membrane; Metal-binding;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..445
FT /note="E3 ubiquitin-protein ligase MYLIP"
FT /id="PRO_0000397121"
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 341..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"
SQ SEQUENCE 445 AA; 49890 MW; 6BF6766F610D6000 CRC64;
MLCYVTRPDA VLMEVEVEAK ANGEDCLNQV CRRLGIIEVD YFGLQFTGSK GESLWLNLRN
RISQQMDGLA PYRLKLRVKF FVEPHLILQE QTRHIFFLHI KESLLAGHLQ CSPEQAVELS
ALLAQTKFGD YNQNTAQYSY EDLCEKELSS STLNSIVGKH KELEGISQAS AEYQVLQIVS
AMENYGIEWH AVRDSEGQKL LIGVGPEGIS ICKEDFSPIN RIAYPVVQMA TQSGKNVYLT
VTKESGNSIV LLFKMISTRA ASGLYRAITE THAFYRCDTV TSAVMMQYSR DLKGHLASLF
LNENINLGKK YVFDIKRTSK EVYDHARRAL YNAGVVDLVS RNDQSPPSSP LKSSDSSMSC
SSCEGLSCQQ TRVLQEKLRK LKEAMLCMVC CEEEINSTFC PCGHTVCCES CAAQLQSCPV
CRSRVEHVQH VYLPTHTSLL NLTVI
