LDLR

Protein identityUniProt · HPA

UniProt accession

P01130

Gene

LDLR

Ensembl

ENSG00000130164

Chromosome

19

Canonical length

860 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles

OverviewNCBI Gene

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]

Canonical amino-acid sequenceUniProt

860 residues, UniProt reviewed canonical sequence.

>P01130|LDLR
     1  MGPWGWKLRW TVALLLAAAG TAVGDRCERN EFQCQDGKCI SYKWVCDGSA ECQDGSDESQ
    61  ETCLSVTCKS GDFSCGGRVN RCIPQFWRCD GQVDCDNGSD EQGCPPKTCS QDEFRCHDGK
   121  CISRQFVCDS DRDCLDGSDE ASCPVLTCGP ASFQCNSSTC IPQLWACDND PDCEDGSDEW
   181  PQRCRGLYVF QGDSSPCSAF EFHCLSGECI HSSWRCDGGP DCKDKSDEEN CAVATCRPDE
   241  FQCSDGNCIH GSRQCDREYD CKDMSDEVGC VNVTLCEGPN KFKCHSGECI TLDKVCNMAR
   301  DCRDWSDEPI KECGTNECLD NNGGCSHVCN DLKIGYECLC PDGFQLVAQR RCEDIDECQD
   361  PDTCSQLCVN LEGGYKCQCE EGFQLDPHTK ACKAVGSIAY LFFTNRHEVR KMTLDRSEYT
   421  SLIPNLRNVV ALDTEVASNR IYWSDLSQRM ICSTQLDRAH GVSSYDTVIS RDIQAPDGLA
   481  VDWIHSNIYW TDSVLGTVSV ADTKGVKRKT LFRENGSKPR AIVVDPVHGF MYWTDWGTPA
   541  KIKKGGLNGV DIYSLVTENI QWPNGITLDL LSGRLYWVDS KLHSISSIDV NGGNRKTILE
   601  DEKRLAHPFS LAVFEDKVFW TDIINEAIFS ANRLTGSDVN LLAENLLSPE DMVLFHNLTQ
   661  PRGVNWCERT TLSNGGCQYL CLPAPQINPH SPKFTCACPD GMLLARDMRS CLTEAEAAVA
   721  TQETSTVRLK VSSTAVRTQH TTTRPVPDTS RLPGATPGLT TVEIVTMSHQ ALGDVAGRGN
   781  EKKPSSVRAL SIVLPIVLLV FLCLGVFLLW KNWRLKNINS INFDNPVYQK TTEDEVHICH
   841  NQDGYSYPSR QMVSLEDDVA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LDLR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

112 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LDLR.

Disease | AllUniProt

Conditions LDLR is implicated in, by any mechanism.

• Hypercholesterolemia, familial, 1 (FHCL1) MIM:143890

Disease | GeneticClinVar

2,015 pathogenic / likely-pathogenic of 4,570 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypercholesterolemia, familial, 1
• Familial hypercholesterolemia
• Cardiovascular phenotype
• Homozygous familial hypercholesterolemia
• Dyslipidemia

ReferencesPubMed · IEDB

Publications for LDLR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.13

gnomAD pLI

0

gnomAD missense Z

0.12

DepMap mean gene effect

-0.21

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance
• amyloid-beta clearance by cellular catabolic process
• artery morphogenesis
• cellular response to fatty acid
• cellular response to low-density lipoprotein particle stimulus
• cholesterol homeostasis
• cholesterol import
• cholesterol metabolic process
• cholesterol transport
• endocytosis
• high-density lipoprotein particle clearance
• intestinal cholesterol absorption
• lipid metabolic process
• lipoprotein catabolic process
• long-term memory
• low-density lipoprotein particle clearance
• negative regulation of amyloid fibril formation
• negative regulation of astrocyte activation
• negative regulation of gene expression
• negative regulation of low-density lipoprotein particle clearance
• negative regulation of microglial cell activation
• negative regulation of protein metabolic process
• negative regulation of receptor recycling
• phagocytosis
• phospholipid transport
• plasma lipoprotein particle clearance
• positive regulation of gene expression
• positive regulation of inflammatory response
• positive regulation of lysosomal protein catabolic process
• positive regulation of triglyceride biosynthetic process
• receptor-mediated endocytosis
• receptor-mediated endocytosis involved in cholesterol transport
• regulation of cholesterol metabolic process
• regulation of phosphatidylcholine catabolic process
• regulation of protein metabolic process
• response to caloric restriction
• retinoid metabolic process

Molecular functions

• amyloid-beta binding
• calcium ion binding
• clathrin heavy chain binding
• identical protein binding
• lipoprotein particle binding
• low-density lipoprotein particle binding
• low-density lipoprotein particle receptor activity
• molecular adaptor activity
• protease binding
• very-low-density lipoprotein particle receptor activity
• virus receptor activity

Cellular components

• apical part of cell
• basolateral plasma membrane
• cell surface
• clathrin-coated endocytic vesicle membrane
• clathrin-coated pit
• early endosome
• endolysosome membrane
• endosome membrane
• external side of plasma membrane
• Golgi apparatus
• late endosome
• low-density lipoprotein particle
• lysosome
• membrane
• PCSK9-LDLR complex
• plasma membrane
• receptor complex
• somatodendritic compartment
• sorting endosome

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Growth factor receptor cysteine-rich domain superfamily
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• LDL receptor-like superfamily
• NOTCH1, EGF-like calcium-binding domain
• Low-density lipoprotein receptor-related
• Low-density lipoprotein receptor domain class A
• Low-density lipoprotein receptor repeat class B
• Calcium-binding EGF domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Cell membrane
• Cholesterol metabolism
• Coated pit
• Disulfide bond
• EGF-like domain
• Endocytosis
• Endosome
• Glycoprotein
• Golgi apparatus
• Host cell receptor for virus entry
• Host-virus interaction
• LDL
• Lipid metabolism
• Lipid transport
• Lysosome
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Steroid metabolism
• Sterol metabolism
• Transmembrane
• Transmembrane helix
• Transport
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of LDLR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRB1
• PGRMC1
• SNX17
• TMEM97
• PCSK9
• LRPAP1
• ARRB2