LRP1 LDL receptor related protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRP1provided by HGNC
Official Full Name: LDL receptor related protein 1provided by HGNC
Primary source: HGNC:HGNC:6692
See related: Ensembl:ENSG00000123384 MIM:107770; AllianceGenome:HGNC:6692
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APR; KPA; LRP; A2MR; CD91; DDH3; APOER; LRP1A; TGFBR5; IGFBP3R; IGFBP-3R; IGFBP3R1
Summary: This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]
Expression: Ubiquitous expression in fat (RPKM 73.6), ovary (RPKM 50.9) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.3

Exon count:: 89

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (57128483..57213361)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (57096318..57181610)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (57522266..57607144)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.
Title: Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.
Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.
Title: Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.
LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer.
Title: LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer.
LRP1 is the cell-surface endocytosis receptor for vaspin in adipocytes.
Title: LRP1 is the cell-surface endocytosis receptor for vaspin in adipocytes.
LRP-1 Binds Fibrinogen in a Sialylation-Dependent Manner: A Quartz Crystal Microbalance Study.
Title: LRP-1 Binds Fibrinogen in a Sialylation-Dependent Manner: A Quartz Crystal Microbalance Study.
Apolipoprotein E-containing lipoproteins and their extracellular interactions with LRP1 affect LPS-induced inflammation.
Title: Apolipoprotein E-containing lipoproteins and their extracellular interactions with LRP1 affect LPS-induced inflammation.
A reactive monocyte subset characterized by low expression of CD91 is expanded during sterile and septic inflammation.
Title: A reactive monocyte subset characterized by low expression of CD91 is expanded during sterile and septic inflammation.
Apolipoprotein E isoforms and their Cys-thiol modifications impact LRP1-mediated metabolism of triglyceride-rich lipoproteins.
Title: Apolipoprotein E isoforms and their Cys-thiol modifications impact LRP1-mediated metabolism of triglyceride-rich lipoproteins.
ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.
Title: ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.
Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.
Title: Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.

Submit: New GeneRIF Correction See all GeneRIFs (331)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Developmental dysplasia of the hip 3 MedGen: C5882750 OMIM: 620690 GeneReviews: Not available	not available
Keratosis pilaris atrophicans MedGen: C0263428 OMIM: 604093 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies susceptibility loci for migraine without aura. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study reveals three susceptibility loci for common migraine in the general population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat downregulates OCLN (occludin) and LRP1 and upregulates AGER (RAGE), and in a RhoA/ROCK1 dependent manner as shown through hydroxyfasudil inhibition in hCMEC/D3 cells	PubMed
	tat	HIV-1 Tat increases in inhibitory synapse number in neurons are dependent on LRP binding and NMDAR activation but not PSD95 ubiquitination	PubMed
	tat	HIV-1 Tat potentiates NMDA-evoked (Ca2+)I responses involve LRP and a Src family kinase via the NOS/sGC/PKG pathway	PubMed
	tat	HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface	PubMed
	tat	HIV-1 Tat and TGF-beta secretion enhance parasite entry in human macrophages by upregulating surface expression of CD91/LRP-1	PubMed
	tat	HIV-1 Tat decreases the scaffolding protein postsynaptic density 95 (PSD95) in synapses via the low-density lipoprotein receptor-related protein (LRP); Tat decreases PSD95 in a concentration-dependent manner	PubMed
	tat	Binding of HIV-1 Tat to LRP inhibits neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor and amyloid beta-protein	PubMed
	tat	LRP binds to the core domain of HIV-1 Tat (amino acids 37-48) and promotes the efficient uptake of Tat into neurons, suggesting Tat may mediate HIV-1 induced neuropathology through disruption of LRP ligands and activation of neuronal genes	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G28611 (e-PCR)
- UniSTS:43044

SHGC-141809 (e-PCR)
- UniSTS:171090

D12S113E (e-PCR)
- UniSTS:147353

RH44498 (e-PCR)
- UniSTS:44747

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables alpha-2 macroglobulin receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables alpha-2 macroglobulin receptor activity	TAS Traceable Author Statement more info	PubMed
enables amyloid-beta binding	IC Inferred by Curator more info
enables apolipoprotein binding	IBA Inferred from Biological aspect of Ancestor more info
enables apolipoprotein binding	IDA Inferred from Direct Assay more info	PubMed
enables apolipoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
enables apolipoprotein receptor activity	TAS Traceable Author Statement more info	PubMed
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables cargo receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables cargo receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cargo receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables cargo receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables clathrin heavy chain binding	IPI Inferred from Physical Interaction more info	PubMed
enables heparan sulfate proteoglycan binding	TAS Traceable Author Statement more info	PubMed
enables lipoprotein particle receptor binding	IC Inferred by Curator more info	PubMed
enables low-density lipoprotein particle receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables scavenger receptor activity	TAS Traceable Author Statement more info	PubMed
enables signaling receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance	NAS Non-traceable Author Statement more info	PubMed
involved_in amyloid-beta clearance	TAS Traceable Author Statement more info	PubMed
involved_in amyloid-beta clearance by cellular catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid-beta clearance by cellular catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid-beta clearance by cellular catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in amyloid-beta clearance by transcytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid-beta clearance by transcytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta clearance by transcytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in aorta morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic cell clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in astrocyte activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amyloid-beta	ISS Inferred from Sequence or Structural Similarity more info
involved_in enzyme-linked receptor protein signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in lipid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in lipoprotein transport	NAS Non-traceable Author Statement more info	PubMed
involved_in lysosomal transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of SMAD protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of Wnt signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of negative regulation of metallopeptidase activity	IC Inferred by Curator more info	PubMed
involved_in negative regulation of platelet-derived growth factor receptor-beta signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of smooth muscle cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in phagocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phagocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of amyloid-beta clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of amyloid-beta clearance	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cholesterol efflux	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of lipid transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of lysosomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein binding	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in receptor internalization	TAS Traceable Author Statement more info	PubMed
involved_in receptor-mediated endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of actin cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cholesterol transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of extracellular matrix disassembly	TAS Traceable Author Statement more info	PubMed
involved_in regulation of phospholipase A2 activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in retinoid metabolic process	TAS Traceable Author Statement more info
involved_in transcytosis	TAS Traceable Author Statement more info	PubMed
involved_in transport across blood-brain barrier	ISS Inferred from Sequence or Structural Similarity more info
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated pit	IEA Inferred from Electronic Annotation more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in focal adhesion	HDA more info	PubMed
located_in lysosomal membrane	HDA more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in microtubule organizing center	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
part_of plasma membrane protein complex	TAS Traceable Author Statement more info	PubMed
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: prolow-density lipoprotein receptor-related protein 1

Names: TbetaR-V/LRP-1/IGFBP-3 receptor; alpha-2-macroglobulin receptor; apolipoprotein E receptor; low density lipoprotein receptor-related protein 1; type V tgf-beta receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016444.2 RefSeqGene

Range

5002..89880

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002332.3 → NP_002323.2 prolow-density lipoprotein receptor-related protein 1 preproprotein

See identical proteins and their annotated locations for NP_002323.2

Status: REVIEWED

Source sequence(s)

AC023237, AC137628, AC137834

Consensus CDS

CCDS8932.1

UniProtKB/Swiss-Prot

Q07954, Q2PP12, Q86SW0, Q8IVG8

Related

ENSP00000243077.3, ENST00000243077.8

Conserved Domains (9) summary

smart00192
Location:3493 → 3526

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:3094 → 3136

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:2982 → 3011

EGF_CA; Calcium-binding EGF-like domain

COG3386
Location:2253 → 2463

YvrE; Sugar lactone lactonase YvrE [Carbohydrate transport and metabolism]

cd00112
Location:3575 → 3609

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam00058
Location:4013 → 4053

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam12662
Location:2962 → 2985

cEGF; Complement Clr-like EGF-like

pfam14670
Location:807 → 842

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00104
Location:71 → 104

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...