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Protein

Low-density lipoprotein receptor

Gene

LDLR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.2 Publications
(Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins.2 Publications
(Microbial infection) Acts as a receptor for Vesicular stomatitis virus.1 Publication
(Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.1 Publication

GO - Molecular functioni

  • amyloid-beta binding Source: Ensembl
  • calcium ion binding Source: InterPro
  • clathrin heavy chain binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • low-density lipoprotein particle binding Source: BHF-UCL
  • low-density lipoprotein particle receptor activity Source: BHF-UCL
  • protease binding Source: BHF-UCL
  • very-low-density lipoprotein particle receptor activity Source: BHF-UCL
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • amyloid-beta clearance Source: ARUK-UCL
  • cellular response to fatty acid Source: Ensembl
  • cellular response to low-density lipoprotein particle stimulus Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol import Source: BHF-UCL
  • cholesterol metabolic process Source: UniProtKB-KW
  • cholesterol transport Source: HGNC
  • chylomicron remnant clearance Source: Reactome
  • endocytosis Source: ProtInc
  • intestinal cholesterol absorption Source: HGNC
  • lipid metabolic process Source: ProtInc
  • lipoprotein catabolic process Source: Ensembl
  • long-term memory Source: ARUK-UCL
  • low-density lipoprotein particle clearance Source: BHF-UCL
  • membrane organization Source: Reactome
  • negative regulation of amyloid fibril formation Source: ARUK-UCL
  • negative regulation of astrocyte activation Source: ARUK-UCL
  • negative regulation of gene expression Source: Ensembl
  • negative regulation of microglial cell activation Source: ARUK-UCL
  • negative regulation of protein metabolic process Source: ARUK-UCL
  • phospholipid transport Source: BHF-UCL
  • plasma lipoprotein particle clearance Source: ARUK-UCL
  • positive regulation of amyloid-beta clearance Source: ARUK-UCL
  • positive regulation of endocytosis Source: ARUK-UCL
  • positive regulation of gene expression Source: Ensembl
  • positive regulation of inflammatory response Source: Ensembl
  • positive regulation of lipoprotein particle clearance Source: ARUK-UCL
  • positive regulation of lysosomal protein catabolic process Source: ARUK-UCL
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • receptor-mediated endocytosis Source: ARUK-UCL
  • receptor-mediated endocytosis involved in cholesterol transport Source: BHF-UCL
  • regulation of cholesterol homeostasis Source: Ensembl
  • regulation of cholesterol metabolic process Source: Ensembl
  • regulation of phosphatidylcholine catabolic process Source: BHF-UCL
  • regulation of protein metabolic process Source: ARUK-UCL
  • response to caloric restriction Source: ARUK-UCL

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processCholesterol metabolism, Endocytosis, Host-virus interaction, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Enzyme and pathway databases

ReactomeiR-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8964026 Chylomicron clearance
R-HSA-8964038 LDL clearance
R-HSA-975634 Retinoid metabolism and transport
SIGNORiP01130

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor
Short name:
LDL receptor
Gene namesi
Name:LDLR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130164.11
HGNCiHGNC:6547 LDLR
MIMi606945 gene
neXtProtiNX_P01130

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 788ExtracellularBy similarityAdd BLAST767
Transmembranei789 – 810HelicalSequence analysisAdd BLAST22
Topological domaini811 – 860Cytoplasmic1 PublicationAdd BLAST50

Keywords - Cellular componenti

Cell membrane, Coated pit, Endosome, Golgi apparatus, LDL, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Familial hypercholesterolemia (FH)52 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA common autosomal dominant disorder characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. The disorder occurs in 2 clinical forms: a mild form that becomes evident in the fourth or fifth decade in individuals carrying heterozygous LDLR mutations; a more severe form that usually manifests in the first two decades of life in individuals with homozygous LDLR mutations.
See also OMIM:143890
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00530427C → W in FH; San Francisco. 1 PublicationCorresponds to variant dbSNP:rs2228671Ensembl.1
Natural variantiVAR_01394946C → S in FH; Japanese patient. 1 PublicationCorresponds to variant dbSNP:rs121908041Ensembl.1
Natural variantiVAR_00530547 – 48Missing in FH; Cape Town-1; retards receptor transport from the endoplasmic reticulum to the cell surface. 2 Publications2
Natural variantiVAR_00797950A → S in FH; German patient. 1 PublicationCorresponds to variant dbSNP:rs137853960Ensembl.1
Natural variantiVAR_07282750A → T in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs137853960Ensembl.1
Natural variantiVAR_00798056S → P in FH. 1 PublicationCorresponds to variant dbSNP:rs878854026Ensembl.1
Natural variantiVAR_00530778R → C in FH. 1 PublicationCorresponds to variant dbSNP:rs370860696Ensembl.1
Natural variantiVAR_00530887W → G in FH; French Canadian-4. 3 PublicationsCorresponds to variant dbSNP:rs121908025Ensembl.1
Natural variantiVAR_00530989C → Y in FH. 2 PublicationsCorresponds to variant dbSNP:rs875989894Ensembl.1
Natural variantiVAR_00531090D → G in FH; London-4. 1 PublicationCorresponds to variant dbSNP:rs771019366Ensembl.1
Natural variantiVAR_00531190D → N in FH. 1 PublicationCorresponds to variant dbSNP:rs749038326Ensembl.1
Natural variantiVAR_00531290D → Y in FH; Durban-1. 1 PublicationCorresponds to variant dbSNP:rs749038326Ensembl.1
Natural variantiVAR_00531392Q → E in FH; Spanish patient. 1 PublicationCorresponds to variant dbSNP:rs774467219Ensembl.1
Natural variantiVAR_00531495C → G in FH; Spanish patient. 1 PublicationCorresponds to variant dbSNP:rs879254456Ensembl.1
Natural variantiVAR_005315101E → K in FH; Lancashire; 6% of American English. 2 PublicationsCorresponds to variant dbSNP:rs144172724Ensembl.1
Natural variantiVAR_005317116C → R in FH; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization. 2 PublicationsCorresponds to variant dbSNP:rs879254482Ensembl.1
Natural variantiVAR_062371134C → F in FH. 1 PublicationCorresponds to variant dbSNP:rs879254514Ensembl.1
Natural variantiVAR_062372134C → W in FH. 1 PublicationCorresponds to variant dbSNP:rs879254515Ensembl.1
Natural variantiVAR_005318140E → K in FH; Philippines/Durban-2/Japan. 3 PublicationsCorresponds to variant dbSNP:rs748944640Ensembl.1
Natural variantiVAR_072828143C → R in FH. 1 PublicationCorresponds to variant dbSNP:rs875989901Ensembl.1
Natural variantiVAR_072829148C → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs879254526Ensembl.1
Natural variantiVAR_072830155C → Y in FH; results in defective LDL binding; does not affect receptor expression at the cell surface. 2 PublicationsCorresponds to variant dbSNP:rs879254536Ensembl.1
Natural variantiVAR_005320160C → Y in FH; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs879254541Ensembl.1
Natural variantiVAR_072831168D → A in FH; unknown pathological significance. 1 Publication1
Natural variantiVAR_005321168D → H in FH; Sephardic/Safed; 10% of the Sephardic Jews. 1 PublicationCorresponds to variant dbSNP:rs200727689Ensembl.1
Natural variantiVAR_005322168D → N in FH; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization. 2 PublicationsCorresponds to variant dbSNP:rs200727689Ensembl.1
Natural variantiVAR_005323168D → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs200727689Ensembl.1
Natural variantiVAR_072832172D → N in FH; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization. 2 PublicationsCorresponds to variant dbSNP:rs879254554Ensembl.1
Natural variantiVAR_005325173C → W in FH. 1 PublicationCorresponds to variant dbSNP:rs769318035Ensembl.1
Natural variantiVAR_005326175D → N in FH; Afrikaner-3; 5-10% of Afrikaners. 1 PublicationCorresponds to variant dbSNP:rs121908033Ensembl.1
Natural variantiVAR_007981175D → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs121908033Ensembl.1
Natural variantiVAR_005327177S → L in FH; Puerto Rico. 4 PublicationsCorresponds to variant dbSNP:rs121908026Ensembl.1
Natural variantiVAR_072833184C → W in FH. 1 PublicationCorresponds to variant dbSNP:rs879254571Ensembl.1
Natural variantiVAR_013951184C → Y in FH; Glasco. 2 PublicationsCorresponds to variant dbSNP:rs121908039Ensembl.1
Natural variantiVAR_005330197C → R in FH; British patient. 1 PublicationCorresponds to variant dbSNP:rs730882085Ensembl.1
Natural variantiVAR_072834211H → L in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254603Ensembl.1
Natural variantiVAR_005331218Missing in FH; Piscataway/Lithuania. 3 Publications1
Natural variantiVAR_005332221D → G in FH; Padova. 6 PublicationsCorresponds to variant dbSNP:rs373822756Ensembl.1
Natural variantiVAR_007982221D → N in FH; German patient. 2 PublicationsCorresponds to variant dbSNP:rs875989906Ensembl.1
Natural variantiVAR_005333221D → Y in FH; Cologne patient. 2 PublicationsCorresponds to variant dbSNP:rs875989906Ensembl.1
Natural variantiVAR_062373222C → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs730882086Ensembl.1
Natural variantiVAR_005336224D → V in FH; Cologne patient. 1 PublicationCorresponds to variant dbSNP:rs879254630Ensembl.1
Natural variantiVAR_005338227D → E in FH; Afrikaner-1/Maine; 65-70% of Afrikaner Americans. 2 PublicationsCorresponds to variant dbSNP:rs121908028Ensembl.1
Natural variantiVAR_005341228E → K in FH; French Canadian-3/Mexico; 2% of French Canadians. 2 PublicationsCorresponds to variant dbSNP:rs121908029Ensembl.1
Natural variantiVAR_005340228E → Q in FH; Tulsa-2. 1 PublicationCorresponds to variant dbSNP:rs121908029Ensembl.1
Natural variantiVAR_005342231C → G in FH; Norwegian patient. 1 PublicationCorresponds to variant dbSNP:rs746091400Ensembl.1
Natural variantiVAR_072835243C → R in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254659Ensembl.1
Natural variantiVAR_005345248C → Y in FH; British patient. 1 PublicationCorresponds to variant dbSNP:rs879254663Ensembl.1
Natural variantiVAR_062374254Q → P in FH. 2 PublicationsCorresponds to variant dbSNP:rs879254667Ensembl.1
Natural variantiVAR_013953261C → F in FH; rare mutation; strongly reduced receptor activity. 1 PublicationCorresponds to variant dbSNP:rs121908040Ensembl.1
Natural variantiVAR_005347266D → E in FH; Cincinnati-1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs139043155Ensembl.1
Natural variantiVAR_062375276C → R in FH. 1 PublicationCorresponds to variant dbSNP:rs879254692Ensembl.1
Natural variantiVAR_072837276C → W in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs146651743Ensembl.1
Natural variantiVAR_005349276C → Y in FH; Syrian patient. 1 PublicationCorresponds to variant dbSNP:rs730882089Ensembl.1
Natural variantiVAR_005350277E → K in FH; patients from Sweden and La Havana; unknown pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs148698650Ensembl.1
Natural variantiVAR_072838285H → Y in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs730882091Ensembl.1
Natural variantiVAR_005351286S → R in FH; Greece-2; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs140241383Ensembl.1
Natural variantiVAR_007983288E → K in FH; German patient. 1 PublicationCorresponds to variant dbSNP:rs368657165Ensembl.1
Natural variantiVAR_072839300R → G in FH; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization. 2 PublicationsCorresponds to variant dbSNP:rs767618089Ensembl.1
Natural variantiVAR_005352301D → A in FH; Greek patient. 1 PublicationCorresponds to variant dbSNP:rs879254714Ensembl.1
Natural variantiVAR_072840301D → G in FH; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization. 3 PublicationsCorresponds to variant dbSNP:rs879254714Ensembl.1
Natural variantiVAR_005354302C → W in FH; Iraki patient. 1 PublicationCorresponds to variant dbSNP:rs879254716Ensembl.1
Natural variantiVAR_005353302C → Y in FH; Spanish patient. 1 PublicationCorresponds to variant dbSNP:rs879254715Ensembl.1
Natural variantiVAR_005357306S → L in FH; Amsterdam; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11547917Ensembl.1
Natural variantiVAR_005358313C → Y in FH. 1 PublicationCorresponds to variants dbSNP:rs875989911 and dbSNP:rs875989910EnsemblEnsembl.1
Natural variantiVAR_072841314G → R in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs72658858Ensembl.1
Natural variantiVAR_005360318C → F in FH; Trieste. 2 PublicationsCorresponds to variant dbSNP:rs879254739Ensembl.1
Natural variantiVAR_062376318C → R in FH. 1 PublicationCorresponds to variant dbSNP:rs879254738Ensembl.1
Natural variantiVAR_072842326S → C in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254747Ensembl.1
Natural variantiVAR_005361327H → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs747507019Ensembl.1
Natural variantiVAR_067196329C → F in FH. 1 PublicationCorresponds to variant dbSNP:rs761954844Ensembl.1
Natural variantiVAR_005362329C → Y in FH; Chinese patient. 1 PublicationCorresponds to variant dbSNP:rs761954844Ensembl.1
Natural variantiVAR_005364338C → S in FH; Japanese patients. 2 PublicationsCorresponds to variant dbSNP:rs879254753Ensembl.1
Natural variantiVAR_005366342D → N in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs139361635Ensembl.1
Natural variantiVAR_005367343G → S in FH; Picardie; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs730882096Ensembl.1
Natural variantiVAR_005368350R → P in FH. 2 PublicationsCorresponds to variant dbSNP:rs875989914Ensembl.1
Natural variantiVAR_072843352C → R in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254769Ensembl.1
Natural variantiVAR_007984356D → Y in FH. 2 PublicationsCorresponds to variant dbSNP:rs767767730Ensembl.1
Natural variantiVAR_062377358C → Y in FH. 2 PublicationsCorresponds to variant dbSNP:rs875989915Ensembl.1
Natural variantiVAR_007985366Q → R in FH. 1 PublicationCorresponds to variant dbSNP:rs746982741Ensembl.1
Natural variantiVAR_005374368C → R in FH; French Canadian patient. 1 PublicationCorresponds to variant dbSNP:rs879254791Ensembl.1
Natural variantiVAR_072844368C → Y in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs768430352Ensembl.1
Natural variantiVAR_062378370N → T in FH. 1 PublicationCorresponds to variant dbSNP:rs879254792Ensembl.1
Natural variantiVAR_072845373G → D in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254797Ensembl.1
Natural variantiVAR_007986379C → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs879254804Ensembl.1
Natural variantiVAR_005376399A → D in FH. 1 PublicationCorresponds to variant dbSNP:rs875989918Ensembl.1
Natural variantiVAR_007987401L → V in FH. 1 PublicationCorresponds to variant dbSNP:rs146200173Ensembl.1
Natural variantiVAR_008995403F → L in FH; Japanese patient. 1 PublicationCorresponds to variant dbSNP:rs879254831Ensembl.1
Natural variantiVAR_072846404T → P in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254834Ensembl.1
Natural variantiVAR_072847406R → W in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121908043Ensembl.1
Natural variantiVAR_005378408E → K in FH; Algeria-1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs137943601Ensembl.1
Natural variantiVAR_005379414L → R in FH; Chinese patient. 1 PublicationCorresponds to variant dbSNP:rs748554592Ensembl.1
Natural variantiVAR_062379415D → G in FH. 1 PublicationCorresponds to variant dbSNP:rs879254845Ensembl.1
Natural variantiVAR_005380416R → Q in FH; German patient. 1 PublicationCorresponds to variant dbSNP:rs773658037Ensembl.1
Natural variantiVAR_005381416R → W in FH; results in reduced receptor expression at the cell surface due to defective receptor recycling. 4 PublicationsCorresponds to variant dbSNP:rs570942190Ensembl.1
Natural variantiVAR_005382423I → T in FH; Swedish patient. 1 PublicationCorresponds to variant dbSNP:rs879254849Ensembl.1
Natural variantiVAR_005383429V → M in FH; Afrikaner-2; 20-30% of Afrikaners and 2% of FH Dutch. 5 PublicationsCorresponds to variant dbSNP:rs28942078Ensembl.1
Natural variantiVAR_005384431A → T in FH; Algeria-2; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs28942079Ensembl.1
Natural variantiVAR_007988432L → V in FH; German patient. 1 PublicationCorresponds to variant dbSNP:rs730882100Ensembl.1
Natural variantiVAR_005385433D → H in FH; Osaka-3. 1 PublicationCorresponds to variant dbSNP:rs121908036Ensembl.1
Natural variantiVAR_005386434T → K in FH; Algeria-3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs745343524Ensembl.1
Natural variantiVAR_072848442Y → H in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879254863Ensembl.1
Natural variantiVAR_062380451I → T in FH. 2 PublicationsCorresponds to variant dbSNP:rs879254874Ensembl.1
Natural variantiVAR_072849454T → N in FH; results in reduced receptor expression at the cell surface due to defective receptor recycling. 2 PublicationsCorresponds to variant dbSNP:rs879254879Ensembl.1
Natural variantiVAR_062381479L → P in FH. 1 PublicationCorresponds to variant dbSNP:rs879254900Ensembl.1
Natural variantiVAR_005391482D → H in FH. 2 PublicationsCorresponds to variant dbSNP:rs139624145Ensembl.1
Natural variantiVAR_005392483W → R in FH. 1 PublicationCorresponds to variant dbSNP:rs879254905Ensembl.1
Natural variantiVAR_005393487Missing in FH; Norwegian patient. 1 Publication1
Natural variantiVAR_072850492D → N in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373646964Ensembl.1
Natural variantiVAR_005395523V → M in FH; Kuwait. 1 PublicationCorresponds to variant dbSNP:rs28942080Ensembl.1
Natural variantiVAR_005396526P → S in FH; Cincinnati-3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs730882106Ensembl.1
Natural variantiVAR_005398549G → D in FH; Genoa. 2 PublicationsCorresponds to variant dbSNP:rs28941776Ensembl.1
Natural variantiVAR_005399564N → H in FH. 5 PublicationsCorresponds to variant dbSNP:rs397509365Ensembl.1
Natural variantiVAR_005400564N → S in FH; Sicily. 1 PublicationCorresponds to variant dbSNP:rs758194385Ensembl.1
Natural variantiVAR_008996568L → V in FH; Japanese patient. 1 PublicationCorresponds to variant dbSNP:rs746959386Ensembl.1
Natural variantiVAR_072851574R → C in FH. 1 PublicationCorresponds to variant dbSNP:rs185098634Ensembl.1
Natural variantiVAR_072852574R → H in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777188764Ensembl.1
Natural variantiVAR_072853577W → G in FH; results in loss of receptor expression at the cell surface. 2 PublicationsCorresponds to variant dbSNP:rs879255000Ensembl.1
Natural variantiVAR_072854577W → S in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138947766Ensembl.1
Natural variantiVAR_005402579D → N in FH; Cincinnati-4; less than 2% receptor activity. 2 PublicationsCorresponds to variant dbSNP:rs875989929Ensembl.1
Natural variantiVAR_062382579D → Y in FH. 1 PublicationCorresponds to variant dbSNP:rs875989929Ensembl.1
Natural variantiVAR_072855585I → T in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879255012Ensembl.1
Natural variantiVAR_005403592G → E in FH; Sicily. 1 PublicationCorresponds to variant dbSNP:rs137929307Ensembl.1
Natural variantiVAR_072856595R → W in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373371572Ensembl.1
Natural variantiVAR_072857601D → H in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs753707206Ensembl.1
Natural variantiVAR_007989608P → S in FH. 1 PublicationCorresponds to variant dbSNP:rs879255034Ensembl.1
Natural variantiVAR_005405633R → C in FH. 1 PublicationCorresponds to variant dbSNP:rs746118995Ensembl.1
Natural variantiVAR_072858639V → D in FH. 1 PublicationCorresponds to variant dbSNP:rs794728584Ensembl.1
Natural variantiVAR_005406649P → L in FH. 1 PublicationCorresponds to variant dbSNP:rs879255081Ensembl.1
Natural variantiVAR_005407667C → Y in FH; French Canadian-2; 5% of French Canadians. 2 PublicationsCorresponds to variant dbSNP:rs28942083Ensembl.1
Natural variantiVAR_005408677C → R in FH; New York-3. 1 PublicationCorresponds to variant dbSNP:rs775092314Ensembl.1
Natural variantiVAR_005410685P → L in FH; Gujerat/Zambia/Belgian/Dutch/Sweden/Japan. 7 PublicationsCorresponds to variant dbSNP:rs28942084Ensembl.1
Natural variantiVAR_013955699P → L in FH; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs201573863Ensembl.1
Natural variantiVAR_005412700D → E in FH; Spanish patient. 1 PublicationCorresponds to variant dbSNP:rs759858813Ensembl.1
Natural variantiVAR_008997714E → K in FH; Japanese patient. 1 PublicationCorresponds to variant dbSNP:rs869320652Ensembl.1
Natural variantiVAR_005413726T → I in FH; Paris-9; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs45508991Ensembl.1
Natural variantiVAR_005415797V → M in FH; La Havana patient. 2 PublicationsCorresponds to variant dbSNP:rs750518671Ensembl.1
Natural variantiVAR_005416799 – 801Missing in FH; Danish patient. 1 Publication3
Natural variantiVAR_072860806V → D in FH; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879255208Ensembl.1
Natural variantiVAR_011864814R → Q in FH; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs5928Ensembl.1
Natural variantiVAR_005417820 – 822Missing in FH. 3
Natural variantiVAR_072861825N → K in FH; does not affect receptor expression at the cell surface; does not affect LDL binding; results in impaired LDL uptake and internalization. 2 PublicationsCorresponds to variant dbSNP:rs374045590Ensembl.1
Natural variantiVAR_062383826P → S in FH. 1 Publication1
Natural variantiVAR_005419828Y → C in FH; J.D.Bari/Syria; 2-fold decreased affinity for LDLRAP1. 2 PublicationsCorresponds to variant dbSNP:rs28942085Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi811K → R: No change. No change; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816; R-830 and A-839. 1 Publication1
Mutagenesisi816K → R: No change. No change; when associated with R-830. No change; when associated with R-811 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-830 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-830 and A-839. 1 Publication1
Mutagenesisi821I → A: 3-fold decreased affinity for LDLRAP1. 1 Publication1
Mutagenesisi821I → R: 10-fold decreased affinity for LDLRAP1. 1 Publication1
Mutagenesisi828Y → A: Abolishes interaction with ARRB2. 1 Publication1
Mutagenesisi829Q → A: Decreased affinity for LDLRAP1. 1 Publication1
Mutagenesisi830K → R: No change. No change; when associated with R-816. No change; when associated with R-811 and R-816. Insensitive to MYLIP-triggered degradation; when associated with A-839. Insensitive to MYLIP-triggered degradation; when associated with R-816 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and A-839. 1 Publication1
Mutagenesisi839C → A: No change. Insensitive to MYLIP-triggered degradation; when associated with R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and R-830. 1 Publication1
Mutagenesisi854S → A: No effect on receptor internalization. 1 Publication1
Mutagenesisi854S → D: Enhances interaction with ARRB2 and receptor internalization. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3949
GeneReviewsiLDLR
MalaCardsiLDLR
MIMi143890 phenotype
OpenTargetsiENSG00000130164
Orphaneti406 Heterozygous familial hypercholesterolemia
391665 Homozygous familial hypercholesterolemia
PharmGKBiPA227

Chemistry databases

ChEMBLiCHEMBL3311
DrugBankiDB00707 Porfimer

Polymorphism and mutation databases

BioMutaiLDLR
DMDMi126073

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000001731222 – 860Low-density lipoprotein receptorAdd BLAST839

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 39
Disulfide bondi34 ↔ 52
Disulfide bondi46 ↔ 63
Disulfide bondi68 ↔ 82
Disulfide bondi75 ↔ 95
Disulfide bondi89 ↔ 104
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi109 ↔ 121By similarity
Disulfide bondi116 ↔ 134
Disulfide bondi128 ↔ 143
Disulfide bondi148 ↔ 160
Disulfide bondi155 ↔ 173
Glycosylationi156N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi167 ↔ 184
Disulfide bondi197 ↔ 209
Disulfide bondi204 ↔ 222
Disulfide bondi216 ↔ 231
Disulfide bondi236 ↔ 248
Disulfide bondi243 ↔ 261
Disulfide bondi255 ↔ 270
Glycosylationi272N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi276 ↔ 289
Disulfide bondi284 ↔ 302
Disulfide bondi296 ↔ 313
Disulfide bondi318 ↔ 329
Disulfide bondi325 ↔ 338
Disulfide bondi340 ↔ 352
Disulfide bondi358 ↔ 368
Disulfide bondi364 ↔ 377
Disulfide bondi379 ↔ 392
Glycosylationi515N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi657N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi667 ↔ 681
Disulfide bondi677 ↔ 696
Disulfide bondi698 ↔ 711
Modified residuei724PhosphothreonineBy similarity1

Post-translational modificationi

N- and O-glycosylated.5 Publications
Ubiquitinated by MYLIP leading to degradation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP01130
MaxQBiP01130
PaxDbiP01130
PeptideAtlasiP01130
PRIDEiP01130

PTM databases

GlyConnecti343
iPTMnetiP01130
PhosphoSitePlusiP01130
UniCarbKBiP01130

Expressioni

Gene expression databases

BgeeiENSG00000130164
CleanExiHS_LDLR
ExpressionAtlasiP01130 baseline and differential
GenevisibleiP01130 HS

Organism-specific databases

HPAiHPA009647
HPA013159

Interactioni

Subunit structurei

Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID domain) (PubMed:12221107, PubMed:22509010). Interacts with ARRB1 (PubMed:12944399). Interacts with SNX17 (PubMed:14739284). Interacts with the full-length immature form of PCSK9 (via C-terminus) (PubMed:17461796, PubMed:21149300).By similarity6 Publications
(Microbial infection) Interacts with vesicular stomatitis virus glycoprotein.1 Publication
(Microbial infection) May interact with HIV-1 Tat.1 Publication

Binary interactionsi

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GO - Molecular functioni

  • clathrin heavy chain binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protease binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110141, 42 interactors
DIPiDIP-29695N
ELMiP01130
IntActiP01130, 20 interactors
MINTiP01130
STRINGi9606.ENSP00000454071

Chemistry databases

BindingDBiP01130

Structurei

Secondary structure

1860
Legend: HelixTurnBeta strandPDB Structure known for this area
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Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi29 – 33Combined sources5
Beta strandi35 – 37Combined sources3
Beta strandi39 – 41Combined sources