Lrp2 LDL receptor related protein 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Lrp2provided by RGD
Official Full Name: LDL receptor related protein 2provided by RGD
Primary source: RGD:68407
See related: Ensembl:ENSRNOG00000056184 AllianceGenome:RGD:68407
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables several functions, including PDZ domain binding activity; insulin-like growth factor I binding activity; and low-density lipoprotein particle receptor binding activity. Involved in several processes, including endocytic hemoglobin import into cell; positive regulation of transport; and response to vitamin D. Located in several cellular components, including apical plasma membrane; axonal growth cone; and brush border membrane. Part of receptor complex. Used to study hypertension. Biomarker of autosomal dominant polycystic kidney disease; end stage renal disease; membranous glomerulonephritis; and nephrosis. Human ortholog(s) of this gene implicated in Donnai-Barrow syndrome and autoimmune thyroiditis. Orthologous to human LRP2 (LDL receptor related protein 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward (RPKM 5350.7) See more
Orthologs: human mouse all
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Genomic context

Location:: 3q21

Exon count:: 79

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (74597148..74754535, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (54189305..54346769, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (55665153..55822484, complement)

Chromosome 3 - NC_086021.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Low Density Lipoprotein Receptor-related Protein 2 Expression and Function in Cultured Astrocytes and Microglia.
Title: Low Density Lipoprotein Receptor-related Protein 2 Expression and Function in Cultured Astrocytes and Microglia.
Angiotensin II type 2 receptor activation preserves megalin in the kidney and prevents proteinuria in high salt diet fed rats.
Title: Angiotensin II type 2 receptor activation preserves megalin in the kidney and prevents proteinuria in high salt diet fed rats.
Megalin: A Novel Endocytic Receptor for Prorenin and Renin.
Title: Megalin: A Novel Endocytic Receptor for Prorenin and Renin.
Renal megalin expression was found to be upregulated in early type 2 diabetic rats in a process that may involve high glucose and insulin in a PI3K/Akt-dependent manner.
Title: Increased megalin expression in early type 2 diabetes: role of insulin-signaling pathways.
Mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of diabetes mellitus.
Title: Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus.
Data suggest that, in acute kidney injury (here, due to cadmium poisoning), kidney exhibits down-regulation of megalin receptor activity; up-regulation of NFkappaB, TLR2 (toll like receptor-2), and TLR4 (toll like receptor-4); and significant reduction in GSH (glutathione).
Title: Relevance of megalin receptor injury with nuclear factor-kappa B upregulation in acute kidney injury induced in rats.
Exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of diabetic nephropathy in T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules.
Title: Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy.
Data suggest both LRP1 and LRP2 are necessary in growth cones for ligand- (zinc metallothionein IIa-)mediated chemotactic calcium-dependent signal transduction in sensory neurons, for axon guidance/neurogenesis, and for peripheral nerve regeneration.
Title: Low-density Lipoprotein Receptor-related Proteins in a Novel Mechanism of Axon Guidance and Peripheral Nerve Regeneration.
Megalin-mediated B12 endocytosis in renal tubules may be regulated by methylmalonic acid.
Title: Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during vitamin B12 deficiency.
The inhibition of megalin/cubilin or lysosomal cathepsin B reduced albuminuria-induced NLRP3 inflammasome activation.
Title: Megalin/Cubulin-Lysosome-mediated Albumin Reabsorption Is Involved in the Tubular Cell Activation of NLRP3 Inflammasome and Tubulointerstitial Inflammation.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH140983 (e-PCR)
- UniSTS:222984

D3Rat239 (e-PCR), detects polymorphism
- UniSTS:227624

UniSTS:485602 (e-PCR)
- UniSTS:485602

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
NOT enables amyloid-beta binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables cargo receptor activity	ISO Inferred from Sequence Orthology more info
enables hemoglobin binding	IDA Inferred from Direct Assay more info	PubMed
enables hormone binding	IBA Inferred from Biological aspect of Ancestor more info
enables hormone binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor I binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-folding chaperone binding	IEA Inferred from Electronic Annotation more info
enables protein-folding chaperone binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in animal organ regeneration	IEP Inferred from Expression Pattern more info	PubMed
involved_in aorta development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within aorta development	ISO Inferred from Sequence Orthology more info
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chemoattraction of axon	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in coronary artery morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in coronary artery morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in coronary artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within coronary vasculature development	ISO Inferred from Sequence Orthology more info
involved_in diol metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within diol metabolic process	ISO Inferred from Sequence Orthology more info
involved_in endocytic hemoglobin import into cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endosomal transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in folate import across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in folate import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in folate import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within heart development	ISO Inferred from Sequence Orthology more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within kidney development	ISO Inferred from Sequence Orthology more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in male gonad development	ISO Inferred from Sequence Orthology more info
involved_in male gonad development	ISS Inferred from Sequence or Structural Similarity more info
involved_in metal ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in metal ion transport	IEA Inferred from Electronic Annotation more info
involved_in metal ion transport	ISO Inferred from Sequence Orthology more info
involved_in metanephric proximal tubule development	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in neural tube closure	ISO Inferred from Sequence Orthology more info
involved_in neural tube closure	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection arborization	IEA Inferred from Electronic Annotation more info
involved_in neuron projection arborization	ISO Inferred from Sequence Orthology more info
involved_in neuron projection arborization	ISS Inferred from Sequence or Structural Similarity more info
involved_in outflow tract septum morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in outflow tract septum morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in outflow tract septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lipoprotein transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lysosomal protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neurogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neurogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of oligodendrocyte progenitor proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of oligodendrocyte progenitor proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of oligodendrocyte progenitor proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in protein transport	ISO Inferred from Sequence Orthology more info
involved_in pulmonary artery morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in pulmonary artery morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in pulmonary artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in receptor-mediated endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor-mediated endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in receptor-mediated endocytosis	IEA Inferred from Electronic Annotation more info
involved_in receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in response to X-ray	IDA Inferred from Direct Assay more info	PubMed
involved_in response to leptin	IEA Inferred from Electronic Annotation more info
involved_in response to leptin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to leptin	ISO Inferred from Sequence Orthology more info
involved_in response to retinoic acid	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to vitamin D	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in secondary heart field specification	IEA Inferred from Electronic Annotation more info
involved_in secondary heart field specification	ISO Inferred from Sequence Orthology more info
involved_in secondary heart field specification	ISS Inferred from Sequence or Structural Similarity more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	ISO Inferred from Sequence Orthology more info
involved_in sensory perception of sound	ISS Inferred from Sequence or Structural Similarity more info
involved_in transcytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vagina development	IEA Inferred from Electronic Annotation more info
involved_in vagina development	ISO Inferred from Sequence Orthology more info
involved_in vagina development	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular compact myocardium morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in ventricular compact myocardium morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in ventricular compact myocardium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular septum development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within ventricular septum development	ISO Inferred from Sequence Orthology more info
involved_in vitamin D metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within vitamin D metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in apical part of cell	ISO Inferred from Sequence Orthology more info
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in axonal growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in brush border	IDA Inferred from Direct Assay more info	PubMed
located_in brush border	ISO Inferred from Sequence Orthology more info
located_in brush border membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border membrane	IEA Inferred from Electronic Annotation more info
located_in brush border membrane	ISO Inferred from Sequence Orthology more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated pit	IEA Inferred from Electronic Annotation more info
located_in clathrin-coated pit	ISO Inferred from Sequence Orthology more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in endocytic vesicle	IEA Inferred from Electronic Annotation more info
located_in endocytic vesicle	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in endosome lumen	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in external side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IEA Inferred from Electronic Annotation more info
part_of receptor complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: low-density lipoprotein receptor-related protein 2

Names: LRP-2; glycoprotein 330; gp330; low density lipoprotein-related protein 2; megalin

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.

mRNA and Protein(s)

NM_030827.2 → NP_110454.2 low-density lipoprotein receptor-related protein 2 precursor

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000003

UniProtKB/Swiss-Prot

P98158

UniProtKB/TrEMBL

A0A0G2K9W7, A6HM07

Related

ENSRNOP00000075159.1, ENSRNOT00000082624.2

Conserved Domains (11) summary

smart00192
Location:2907 → 2939

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:1502 → 1544

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:1391 → 1430

EGF_CA; Calcium-binding EGF-like domain

COG3391
Location:2110 → 2302

YncE; DNA-binding beta-propeller fold protein YncE [General function prediction only]

cd00112
Location:3761 → 3795

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 ...

pfam00057
Location:1065 → 1101

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:1884 → 1928

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam12662
Location:3134 → 3157

cEGF; Complement Clr-like EGF-like

pfam14670
Location:2023 → 2059

FXa_inhibition; Coagulation Factor Xa inhibitory site

NF033759
Location:2743 → 3131

exchanger_TraA; outer membrane exchange protein TraA

cl39070
Location:837 → 877

Ldl_recept_b; Low-density lipoprotein receptor repeat class B