VLDLR_HUMAN
ID VLDLR_HUMAN Reviewed; 873 AA.
AC P98155; B2RMZ7; D3DRH6; Q5VVF6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Very low-density lipoprotein receptor;
DE Short=VLDL receptor;
DE Short=VLDL-R;
DE Flags: Precursor;
GN Name=VLDLR;
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].
RC TISSUE=Skeletal muscle;
RX PubMed=8128315; DOI=10.1007/bf01233382;
RA Gafvels M.E., Caird M., Britt D., Jackson C.L., Patterson D., Strauss J.F.;
RT "Cloning of a cDNA encoding a putative human very low density
RT lipoprotein/apolipoprotein E receptor and assignment of the gene to
RT chromosome 9pter-p23.";
RL Somat. Cell Mol. Genet. 19:557-569(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8069294; DOI=10.1093/hmg/3.4.531;
RA Webb J.C., Patel D.D., Jones M.D., Knight B.L., Soutar A.K.;
RT "Characterization and tissue-specific expression of the human 'very low
RT density lipoprotein (VLDL) receptor' mRNA.";
RL Hum. Mol. Genet. 3:531-537(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8294473; DOI=10.1016/s0021-9258(17)42151-x;
RA Sakai J., Hoshino A., Takahashi S., Miura Y., Ishii H., Suzuki H.,
RA Kawarabayasi Y., Yamamoto T.;
RT "Structure, chromosome location, and expression of the human very low
RT density lipoprotein receptor gene.";
RL J. Biol. Chem. 269:2173-2182(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8020981; DOI=10.1006/geno.1994.1171;
RA Oka K., Tzung K.W., Sullivan M., Lindsay E., Baldini A., Chan L.;
RT "Human very-low-density lipoprotein receptor complementary DNA and deduced
RT amino acid sequence and localization of its gene (VLDLR) to chromosome band
RT 9p24 by fluorescence in situ hybridization.";
RL Genomics 20:298-300(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-59; HIS-262; ILE-464;
RP VAL-561; HIS-613 AND ILE-791.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
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 INTERACTION WITH HRV VP1 (MICROBIAL INFECTION).
RX PubMed=12857919; DOI=10.1128/jvi.77.15.8504-8511.2003;
RA Neumann E., Moser R., Snyers L., Blaas D., Hewat E.A.;
RT "A cellular receptor of human rhinovirus type 2, the very-low-density
RT lipoprotein receptor, binds to two neighboring proteins of the viral
RT capsid.";
RL J. Virol. 77:8504-8511(2003).
RN [10]
RP INTERACTION WITH PAFAH1B3 AND PAFAH1B2.
RX PubMed=17330141; DOI=10.1371/journal.pone.0000252;
RA Zhang G., Assadi A.H., McNeil R.S., Beffert U., Wynshaw-Boris A., Herz J.,
RA Clark G.D., D'Arcangelo G.;
RT "The Pafah1b complex interacts with the reelin receptor VLDLR.";
RL PLoS ONE 2:e252-e252(2007).
RN [11]
RP INTERACTION WITH PCSK9.
RX PubMed=18039658; DOI=10.1074/jbc.m708098200;
RA Poirier S., Mayer G., Benjannet S., Bergeron E., Marcinkiewicz J.,
RA Nassoury N., Mayer H., Nimpf J., Prat A., Seidah N.G.;
RT "The proprotein convertase PCSK9 induces the degradation of low density
RT lipoprotein receptor (LDLR) and its closest family members VLDLR and
RT ApoER2.";
RL J. Biol. Chem. 283:2363-2372(2008).
RN [12]
RP UBIQUITINATION AT LYS-839 BY MYLIP, GLYCOSYLATION, AND MUTAGENESIS OF
RP LYS-825; LYS-828 AND LYS-839.
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 INTERACTION WITH STX5, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=23701949; DOI=10.1016/j.yexcr.2013.05.010;
RA Wagner T., Dieckmann M., Jaeger S., Weggen S., Pietrzik C.U.;
RT "Stx5 is a novel interactor of VLDL-R to affect its intracellular
RT trafficking and processing.";
RL Exp. Cell Res. 319:1956-1972(2013).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CLU.
RX PubMed=24381170; DOI=10.1074/jbc.m113.529271;
RA Leeb C., Eresheim C., Nimpf J.;
RT "Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very
RT low density lipoprotein receptor (VLDLR) and signals via the Reelin-
RT signaling pathway.";
RL J. Biol. Chem. 289:4161-4172(2014).
RN [15]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH RELN AND
RP LRP8.
RX PubMed=30873003; DOI=10.3389/fnmol.2019.00053;
RA Dlugosz P., Tresky R., Nimpf J.;
RT "Differential Action of Reelin on Oligomerization of ApoER2 and VLDL
RT Receptor in HEK293 Cells Assessed by Time-Resolved Anisotropy and
RT Fluorescence Lifetime Imaging Microscopy.";
RL Front. Mol. Neurosci. 12:53-53(2019).
RN [16]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SEMLIKI FOREST VIRUS E2-E1
RP HETERODIMER (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=34929721; DOI=10.1038/s41586-021-04326-0;
RA Clark L.E., Clark S.A., Lin C., Liu J., Coscia A., Nabel K.G., Yang P.,
RA Neel D.V., Lee H., Brusic V., Stryapunina I., Plante K.S., Ahmed A.A.,
RA Catteruccia F., Young-Pearse T.L., Chiu I.M., Llopis P.M., Weaver S.C.,
RA Abraham J.;
RT "VLDLR and ApoER2 are receptors for multiple alphaviruses.";
RL Nature 602:475-480(2022).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 111-151 IN COMPLEX WITH HRV2.
RX PubMed=15064754; DOI=10.1038/nsmb753;
RA Verdaguer N., Fita I., Reithmayer M., Moser R., Blaas D.;
RT "X-ray structure of a minor group human rhinovirus bound to a fragment of
RT its cellular receptor protein.";
RL Nat. Struct. Mol. Biol. 11:429-434(2004).
RN [18]
RP VARIANTS ILE-59 AND LYS-379.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [19]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [20]
RP INVOLVEMENT IN CAMRQ1.
RX PubMed=16080122; DOI=10.1086/444400;
RA Boycott K.M., Flavelle S., Bureau A., Glass H.C., Fujiwara T.M.,
RA Wirrell E., Davey K., Chudley A.E., Scott J.N., McLeod D.R.,
RA Parboosingh J.S.;
RT "Homozygous deletion of the very low density lipoprotein receptor gene
RT causes autosomal recessive cerebellar hypoplasia with cerebral gyral
RT simplification.";
RL Am. J. Hum. Genet. 77:477-483(2005).
CC -!- FUNCTION: Multifunctional cell surface receptor that binds VLDL and
CC transports it into cells by endocytosis and therefore plays an
CC important role in energy metabolism. Binds also to a wide range of
CC other molecules including Reelin/RELN or apolipoprotein E/APOE-
CC containing ligands as well as clusterin/CLU (PubMed:24381170,
CC PubMed:30873003). In the off-state of the pathway, forms homooligomers
CC or heterooligomers with LRP8 (PubMed:30873003). Upon binding to
CC ligands, homooligomers are rearranged to higher order receptor clusters
CC that transmit the extracellular RELN signal to intracellular signaling
CC processes by binding to DAB1 (PubMed:30873003). This interaction
CC results in phosphorylation of DAB1 leading to the ultimate cell
CC responses required for the correct positioning of newly generated
CC neurons. Later, mediates a stop signal for migrating neurons,
CC preventing them from entering the marginal zone (By similarity).
CC {ECO:0000250|UniProtKB:P98156, ECO:0000269|PubMed:24381170,
CC ECO:0000269|PubMed:30873003}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Semliki Forest
CC virus. {ECO:0000269|PubMed:34929721}.
CC -!- SUBUNIT: Homooligomer (PubMed:30873003). Binds to the extracellular
CC matrix protein Reelin/RELN (PubMed:30873003). Interacts with LRP8
CC (PubMed:30873003). Interacts with LDLRAP1 (By similarity). Interacts
CC with SNX17 (By similarity). Interacts with DAB1. Interacts with PCSK9.
CC Interacts with PAFAH1B3 and PAFAH1B2, the catalytic complex of (PAF-AH
CC (I)) heterotetrameric enzyme; these interactions may modulate the
CC Reelin pathway (PubMed:17330141). Interacts with STX5; this interaction
CC mediates VLDLR translocation from the endoplasmic reticulum to the
CC plasma membrane (PubMed:23701949). Interacts with CLU
CC (PubMed:24381170). {ECO:0000250|UniProtKB:P98156,
CC ECO:0000269|PubMed:15064754, ECO:0000269|PubMed:17330141,
CC ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:23701949,
CC ECO:0000269|PubMed:30873003}.
CC -!- SUBUNIT: (Microbial infection) Interacts with protein VP1 of the minor-
CC group human rhinoviruses (HRVs) through the second and third LDL-
CC receptor class A domains. {ECO:0000269|PubMed:12857919}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Semliki Forest virus E2-
CC E1 heterodimer; this interaction mediates viral entry to host cell.
CC {ECO:0000269|PubMed:34929721}.
CC -!- INTERACTION:
CC P98155; P30533: LRPAP1; NbExp=5; IntAct=EBI-9004309, EBI-715927;
CC P98155; Q99068: Lrpap1; Xeno; NbExp=2; IntAct=EBI-9004309, EBI-919734;
CC P98155; Q60841: Reln; Xeno; NbExp=7; IntAct=EBI-9004309, EBI-9248666;
CC P98155-2; O43309: ZSCAN12; NbExp=3; IntAct=EBI-12047495, EBI-1210440;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23701949,
CC ECO:0000269|PubMed:34929721}; Single-pass type I membrane protein.
CC Membrane, clathrin-coated pit; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P98155-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P98155-2; Sequence=VSP_004304;
CC -!- TISSUE SPECIFICITY: Abundant in heart and skeletal muscle; also ovary
CC and kidney; not in liver.
CC -!- PTM: Ubiquitinated at Lys-839 by MYLIP leading to degradation.
CC {ECO:0000269|PubMed:20427281}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:23701949}.
CC -!- DISEASE: Cerebellar ataxia, intellectual disability, and dysequilibrium
CC syndrome 1 (CAMRQ1) [MIM:224050]: An autosomal recessive, congenital,
CC non-progressive cerebellar ataxia associated with disturbed
CC equilibrium, delayed ambulation, intellectual disability, cerebellar
CC hypoplasia and mild cerebral gyral simplification. Additional features
CC include short stature, strabismus, pes planus and, rarely, seizures.
CC {ECO:0000269|PubMed:16080122}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/vldlr/";
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DR EMBL; L20470; AAA53684.1; -; mRNA.
DR EMBL; S73849; AAB31735.1; -; mRNA.
DR EMBL; D16532; BAA03969.1; -; Genomic_DNA.
DR EMBL; D16493; BAA03945.1; -; mRNA.
DR EMBL; D16494; BAA03946.1; -; mRNA.
DR EMBL; L22431; AAA61344.1; -; mRNA.
DR EMBL; DQ067198; AAY46157.1; -; Genomic_DNA.
DR EMBL; AL450467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58805.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58806.1; -; Genomic_DNA.
DR EMBL; BC136562; AAI36563.1; -; mRNA.
DR CCDS; CCDS34979.1; -. [P98155-2]
DR CCDS; CCDS6446.1; -. [P98155-1]
DR PIR; A49729; A49729.
DR RefSeq; NP_001018066.1; NM_001018056.2. [P98155-2]
DR RefSeq; NP_003374.3; NM_003383.4. [P98155-1]
DR PDB; 1V9U; X-ray; 3.60 A; 5=111-151.
DR PDB; 3DPR; X-ray; 3.50 A; E=113-151.
DR PDB; 6BYV; NMR; -; A=70-190.
DR PDBsum; 1V9U; -.
DR PDBsum; 3DPR; -.
DR PDBsum; 6BYV; -.
DR AlphaFoldDB; P98155; -.
DR SMR; P98155; -.
DR BioGRID; 113277; 30.
DR DIP; DIP-40925N; -.
DR IntAct; P98155; 9.
DR STRING; 9606.ENSP00000371532; -.
DR DrugBank; DB14003; alpha-Tocopherol acetate.
DR DrugBank; DB06755; Beta carotene.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB11251; Tocopherol.
DR DrugBank; DB09270; Ubidecarenone.
DR GlyGen; P98155; 6 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P98155; -.
DR PhosphoSitePlus; P98155; -.
DR BioMuta; VLDLR; -.
DR DMDM; 1730111; -.
DR EPD; P98155; -.
DR jPOST; P98155; -.
DR MassIVE; P98155; -.
DR MaxQB; P98155; -.
DR PaxDb; P98155; -.
DR PeptideAtlas; P98155; -.
DR PRIDE; P98155; -.
DR ProteomicsDB; 57794; -. [P98155-1]
DR ProteomicsDB; 57795; -. [P98155-2]
DR Antibodypedia; 9217; 489 antibodies from 36 providers.
DR DNASU; 7436; -.
DR Ensembl; ENST00000382100.8; ENSP00000371532.2; ENSG00000147852.17. [P98155-1]
DR Ensembl; ENST00000681306.1; ENSP00000506072.1; ENSG00000147852.17. [P98155-2]
DR GeneID; 7436; -.
DR KEGG; hsa:7436; -.
DR MANE-Select; ENST00000382100.8; ENSP00000371532.2; NM_003383.5; NP_003374.3.
DR UCSC; uc003zhk.2; human. [P98155-1]
DR CTD; 7436; -.
DR DisGeNET; 7436; -.
DR GeneCards; VLDLR; -.
DR GeneReviews; VLDLR; -.
DR HGNC; HGNC:12698; VLDLR.
DR HPA; ENSG00000147852; Tissue enhanced (ovary).
DR MalaCards; VLDLR; -.
DR MIM; 192977; gene.
DR MIM; 224050; phenotype.
DR neXtProt; NX_P98155; -.
DR OpenTargets; ENSG00000147852; -.
DR Orphanet; 1766; Dysequilibrium syndrome.
DR PharmGKB; PA37317; -.
DR VEuPathDB; HostDB:ENSG00000147852; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000155460; -.
DR HOGENOM; CLU_008163_2_0_1; -.
DR InParanoid; P98155; -.
DR OMA; DEYACKN; -.
DR OrthoDB; 359795at2759; -.
DR PhylomeDB; P98155; -.
DR TreeFam; TF351700; -.
DR PathwayCommons; P98155; -.
DR Reactome; R-HSA-8866376; Reelin signalling pathway.
DR Reactome; R-HSA-8866427; VLDLR internalisation and degradation.
DR Reactome; R-HSA-8964046; VLDL clearance.
DR SignaLink; P98155; -.
DR SIGNOR; P98155; -.
DR BioGRID-ORCS; 7436; 10 hits in 1069 CRISPR screens.
DR ChiTaRS; VLDLR; human.
DR EvolutionaryTrace; P98155; -.
DR GeneWiki; VLDL_receptor; -.
DR GenomeRNAi; 7436; -.
DR Pharos; P98155; Tbio.
DR PRO; PR:P98155; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P98155; protein.
DR Bgee; ENSG00000147852; Expressed in heart right ventricle and 187 other tissues.
DR ExpressionAtlas; P98155; baseline and differential.
DR Genevisible; P98155; HS.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0034185; F:apolipoprotein binding; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:BHF-UCL.
DR GO; GO:0038024; F:cargo receptor activity; IDA:BHF-UCL.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; TAS:ProtInc.
DR GO; GO:0038025; F:reelin receptor activity; ISS:BHF-UCL.
DR GO; GO:0034189; F:very-low-density lipoprotein particle binding; IDA:BHF-UCL.
DR GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0034436; P:glycoprotein transport; IDA:BHF-UCL.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0007613; P:memory; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISS:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:BHF-UCL.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0021517; P:ventral spinal cord development; IEA:Ensembl.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; IDA:BHF-UCL.
DR CDD; cd00112; LDLa; 8.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 4.10.400.10; -; 8.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR032931; VLDLR.
DR PANTHER; PTHR24270:SF16; PTHR24270:SF16; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00057; Ldl_recept_a; 8.
DR Pfam; PF00058; Ldl_recept_b; 5.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00192; LDLa; 8.
DR SMART; SM00135; LY; 5.
DR SUPFAM; SSF57424; SSF57424; 8.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS01209; LDLRA_1; 8.
DR PROSITE; PS50068; LDLRA_2; 8.
DR PROSITE; PS51120; LDLRB; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cholesterol metabolism;
KW Coated pit; Disulfide bond; EGF-like domain; Endocytosis; Glycoprotein;
KW Host-virus interaction; Intellectual disability; Isopeptide bond;
KW Lipid metabolism; Lipid transport; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; VLDL.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..873
FT /note="Very low-density lipoprotein receptor"
FT /id="PRO_0000017343"
FT TOPO_DOM 28..797
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 798..819
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 820..873
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..69
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 70..110
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 111..151
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 152..190
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 191..231
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 237..275
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 276..314
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 316..355
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 356..395
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 396..435
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 439..480
FT /note="LDL-receptor class B 1"
FT REPEAT 481..524
FT /note="LDL-receptor class B 2"
FT REPEAT 525..567
FT /note="LDL-receptor class B 3"
FT REPEAT 568..611
FT /note="LDL-receptor class B 4"
FT REPEAT 612..654
FT /note="LDL-receptor class B 5"
FT REPEAT 655..697
FT /note="LDL-receptor class B 6"
FT DOMAIN 702..750
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 751..790
FT /note="Clustered O-linked oligosaccharides"
FT MOTIF 832..837
FT /note="Endocytosis signal"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..45
FT /evidence="ECO:0000250"
FT DISULFID 40..58
FT /evidence="ECO:0000250"
FT DISULFID 52..67
FT /evidence="ECO:0000250"
FT DISULFID 72..84
FT /evidence="ECO:0000250"
FT DISULFID 79..97
FT /evidence="ECO:0000250"
FT DISULFID 91..108
FT /evidence="ECO:0000250"
FT DISULFID 113..127
FT DISULFID 120..140
FT DISULFID 134..149
FT DISULFID 154..166
FT /evidence="ECO:0000250"
FT DISULFID 161..179
FT /evidence="ECO:0000250"
FT DISULFID 173..188
FT /evidence="ECO:0000250"
FT DISULFID 193..205
FT /evidence="ECO:0000250"
FT DISULFID 200..218
FT /evidence="ECO:0000250"
FT DISULFID 212..229
FT /evidence="ECO:0000250"
FT DISULFID 239..251
FT /evidence="ECO:0000250"
FT DISULFID 246..264
FT /evidence="ECO:0000250"
FT DISULFID 258..273
FT /evidence="ECO:0000250"
FT DISULFID 278..290
FT /evidence="ECO:0000250"
FT DISULFID 285..303
FT /evidence="ECO:0000250"
FT DISULFID 297..312
FT /evidence="ECO:0000250"
FT DISULFID 318..331
FT /evidence="ECO:0000250"
FT DISULFID 326..344
FT /evidence="ECO:0000250"
FT DISULFID 338..355
FT /evidence="ECO:0000250"
FT DISULFID 360..371
FT /evidence="ECO:0000250"
FT DISULFID 367..380
FT /evidence="ECO:0000250"
FT DISULFID 382..394
FT /evidence="ECO:0000250"
FT DISULFID 400..410
FT /evidence="ECO:0000250"
FT DISULFID 406..419
FT /evidence="ECO:0000250"
FT DISULFID 421..434
FT /evidence="ECO:0000250"
FT DISULFID 706..719
FT /evidence="ECO:0000250"
FT DISULFID 715..734
FT /evidence="ECO:0000250"
FT DISULFID 736..749
FT /evidence="ECO:0000250"
FT CROSSLNK 839
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20427281"
FT VAR_SEQ 751..779
FT /note="STATTVTYSETKDTNTTEISATSGLVPGG -> R (in isoform
FT Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_004304"
FT VARIANT 59
FT /note="V -> I (in dbSNP:rs6149)"
FT /evidence="ECO:0000269|PubMed:10391209, ECO:0000269|Ref.5"
FT /id="VAR_011865"
FT VARIANT 262
FT /note="P -> H (in dbSNP:rs34761707)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025063"
FT VARIANT 379
FT /note="E -> K (in dbSNP:rs6146)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011866"
FT VARIANT 464
FT /note="L -> I (in dbSNP:rs34753566)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025064"
FT VARIANT 561
FT /note="I -> V (in dbSNP:rs35724190)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025065"
FT VARIANT 613
FT /note="R -> H (in dbSNP:rs35948251)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025066"
FT VARIANT 791
FT /note="V -> I (in dbSNP:rs35334949)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025067"
FT MUTAGEN 825
FT /note="K->R: Insensitive to MYLIP-triggered degradation;
FT when associated with R-828 and R-839."
FT /evidence="ECO:0000269|PubMed:20427281"
FT MUTAGEN 828
FT /note="K->R: Insensitive to MYLIP-triggered degradation;
FT when associated with R-825 and R-839."
FT /evidence="ECO:0000269|PubMed:20427281"
FT MUTAGEN 839
FT /note="K->R: Insensitive to MYLIP-triggered degradation.
FT Insensitive to MYLIP-triggered degradation; when associated
FT with R-825 and R-828."
FT /evidence="ECO:0000269|PubMed:20427281"
FT CONFLICT 9
FT /note="L -> V (in Ref. 1; AAA53684)"
FT /evidence="ECO:0000305"
FT CONFLICT 13
FT /note="L -> V (in Ref. 4; AAA61344)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="G -> A (in Ref. 1; AAA53684)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="L -> H (in Ref. 1; AAA53684)"
FT /evidence="ECO:0000305"
FT CONFLICT 766
FT /note="T -> S (in Ref. 4; AAA61344)"
FT /evidence="ECO:0000305"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:6BYV"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:6BYV"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:6BYV"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:6BYV"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:3DPR"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:3DPR"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:3DPR"
FT TURN 141..145
FT /evidence="ECO:0007829|PDB:3DPR"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:6BYV"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6BYV"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:6BYV"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:6BYV"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:6BYV"
SQ SEQUENCE 873 AA; 96098 MW; 8BAC29438A78C2B8 CRC64;
MGTSALWALW LLLALCWAPR ESGATGTGRK AKCEPSQFQC TNGRCITLLW KCDGDEDCVD
GSDEKNCVKK TCAESDFVCN NGQCVPSRWK CDGDPDCEDG SDESPEQCHM RTCRIHEISC
GAHSTQCIPV SWRCDGENDC DSGEDEENCG NITCSPDEFT CSSGRCISRN FVCNGQDDCS
DGSDELDCAP PTCGAHEFQC STSSCIPISW VCDDDADCSD QSDESLEQCG RQPVIHTKCP
ASEIQCGSGE CIHKKWRCDG DPDCKDGSDE VNCPSRTCRP DQFECEDGSC IHGSRQCNGI
RDCVDGSDEV NCKNVNQCLG PGKFKCRSGE CIDISKVCNQ EQDCRDWSDE PLKECHINEC
LVNNGGCSHI CKDLVIGYEC DCAAGFELID RKTCGDIDEC QNPGICSQIC INLKGGYKCE
CSRGYQMDLA TGVCKAVGKE PSLIFTNRRD IRKIGLERKE YIQLVEQLRN TVALDADIAA
QKLFWADLSQ KAIFSASIDD KVGRHVKMID NVYNPAAIAV DWVYKTIYWT DAASKTISVA
TLDGTKRKFL FNSDLREPAS IAVDPLSGFV YWSDWGEPAK IEKAGMNGFD RRPLVTADIQ
WPNGITLDLI KSRLYWLDSK LHMLSSVDLN GQDRRIVLKS LEFLAHPLAL TIFEDRVYWI
DGENEAVYGA NKFTGSELAT LVNNLNDAQD IIVYHELVQP SGKNWCEEDM ENGGCEYLCL
PAPQINDHSP KYTCSCPSGY NVEENGRDCQ STATTVTYSE TKDTNTTEIS ATSGLVPGGI
NVTTAVSEVS VPPKGTSAAW AILPLLLLVM AAVGGYLMWR NWQHKNMKSM NFDNPVYLKT
TEEDLSIDIG RHSASVGHTY PAISVVSTDD DLA
