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LRP2 LDL receptor related protein 2 [ Homo sapiens (human) ]

Gene ID: 4036, updated on 5-Aug-2018

Summary

Official Symbol
LRP2provided by HGNC
Official Full Name
LDL receptor related protein 2provided by HGNC
Primary source
HGNC:HGNC:6694
See related
Ensembl:ENSG00000081479 MIM:600073; Vega:OTTHUMG00000132179
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
DBS; GP330
Summary
The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]
Expression
Biased expression in kidney (RPKM 33.6), thyroid (RPKM 14.6) and 1 other tissue See more
Orthologs

Genomic context

See LRP2 in Genome Data Viewer
Location:
2q31.1
Exon count:
80
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (169127109..169362612, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (169983619..170219123, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene dehydrogenase/reductase 9 Neighboring gene ubiquitin conjugating enzyme E2 V1 pseudogene 6 Neighboring gene Bardet-Biedl syndrome 5 Neighboring gene kelch like family member 41

Genomic regions, transcripts, and products

Expression

  • Project title: 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Donnai Barrow syndrome
MedGen: C1857277 OMIM: 222448 GeneReviews: Donnai-Barrow Syndrome
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa.
NHGRI GWA Catalog
Gene-Smoking Interactions Identify Several Novel Blood Pressure Loci in the Framingham Heart Study.
NHGRI GWA Catalog
Genome-wide association study of hematological and biochemical traits in a Japanese population.
NHGRI GWA Catalog

Pathways from BioSystems

  • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
  • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
  • Hedgehog signaling pathway, organism-specific biosystem (from KEGG)
    Hedgehog signaling pathway, organism-specific biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
  • Hedgehog signaling pathway, conserved biosystem (from KEGG)
    Hedgehog signaling pathway, conserved biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of fat-soluble vitamins, organism-specific biosystem (from REACTOME)
    Metabolism of fat-soluble vitamins, organism-specific biosystemVitamins A, D, E, and K are classified as fat-soluble. Metabolic pathways by which dietary precursors of vitamins A (Harrison 2005) and K(Shearer et al. 2012) are converted to active forms, and by wh...
  • Metabolism of vitamins and cofactors, organism-specific biosystem (from REACTOME)
    Metabolism of vitamins and cofactors, organism-specific biosystemVitamins are a diverse group of organic compounds, classified according to their solubility, either fat-soluble or water-soluble, that are either not synthesized or synthesized only in limited amount...
  • Retinoid metabolism and transport, organism-specific biosystem (from REACTOME)
    Retinoid metabolism and transport, organism-specific biosystemVitamin A (all-trans-retinol) must be taken up, either as carotenes from plants, or as retinyl esters from animal food. The most prominent carotenes are alpha-carotene, lycopene, lutein, beta-cryptox...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling events mediated by the Hedgehog family, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by the Hedgehog family, organism-specific biosystem
    Signaling events mediated by the Hedgehog family
  • Thyroid hormone synthesis, organism-specific biosystem (from KEGG)
    Thyroid hormone synthesis, organism-specific biosystemThyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The function...
  • Thyroid hormone synthesis, conserved biosystem (from KEGG)
    Thyroid hormone synthesis, conserved biosystemThyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The function...
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
  • Visual phototransduction, organism-specific biosystem (from REACTOME)
    Visual phototransduction, organism-specific biosystemVisual phototransduction is the process by which photon absorption by visual pigment molecules in photoreceptor cells is converted to an electrical cellular response. The events in this process are p...
  • Vitamin B12 Metabolism, organism-specific biosystem (from WikiPathways)
    Vitamin B12 Metabolism, organism-specific biosystem
    Vitamin B12 Metabolism
  • Vitamin D (calciferol) metabolism, organism-specific biosystem (from REACTOME)
    Vitamin D (calciferol) metabolism, organism-specific biosystemVitamin D3 (cholecalciferol) is a steroid hormone that plays a role in regulating calcium and bone metabolism. It is obtained from the diet and produced in the skin by photolysis of 7-dehydrocholeste...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SH3 domain binding IEA
Inferred from Electronic Annotation
more info
 
calcium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
chaperone binding IPI
Inferred from Physical Interaction
more info
PubMed 
chaperone binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
drug binding ISS
Inferred from Sequence or Structural Similarity
more info
 
lipoprotein transporter activity TAS
Traceable Author Statement
more info
 
low-density lipoprotein particle receptor activity TAS
Traceable Author Statement
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
steroid hormone receptor binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
aorta development IEA
Inferred from Electronic Annotation
more info
 
cell proliferation IEA
Inferred from Electronic Annotation
more info
 
coronary artery morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
endocytosis TAS
Traceable Author Statement
more info
PubMed 
folate import across plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
forebrain development IEA
Inferred from Electronic Annotation
more info
 
lipid metabolic process TAS
Traceable Author Statement
more info
PubMed 
lipoprotein transport IEA
Inferred from Electronic Annotation
more info
 
male gonad development ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane organization TAS
Traceable Author Statement
more info
 
metal ion transport IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
neural tube closure ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron projection arborization ISS
Inferred from Sequence or Structural Similarity
more info
 
outflow tract septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of lysosomal protein catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of oligodendrocyte progenitor proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
pulmonary artery morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
receptor-mediated endocytosis IDA
Inferred from Direct Assay
more info
PubMed 
receptor-mediated endocytosis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
retinoid metabolic process TAS
Traceable Author Statement
more info
 
secondary heart field specification ISS
Inferred from Sequence or Structural Similarity
more info
 
sensory perception of sound ISS
Inferred from Sequence or Structural Similarity
more info
 
vagina development ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular compact myocardium morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular septum development IEA
Inferred from Electronic Annotation
more info
 
vitamin D metabolic process TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
Golgi apparatus IEA
Inferred from Electronic Annotation
more info
 
apical plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
axon ISS
Inferred from Sequence or Structural Similarity
more info
 
brush border membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
clathrin-coated pit IEA
Inferred from Electronic Annotation
more info
 
clathrin-coated vesicle membrane TAS
Traceable Author Statement
more info
 
dendrite ISS
Inferred from Sequence or Structural Similarity
more info
 
endocytic vesicle IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
endosome lumen IEA
Inferred from Electronic Annotation
more info
 
external side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
extracellular exosome HDA PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
lysosomal membrane HDA PubMed 
lysosome TAS
Traceable Author Statement
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
receptor complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
low-density lipoprotein receptor-related protein 2
Names
Heymann nephritis antigen homolog
LRP-2
calcium sensor protein
glycoprotein 330
megalin

NCBI Reference Sequences (RefSeq)

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

  1. NG_012634.1 RefSeqGene

    Range
    5001..240504
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004525.2NP_004516.2  low-density lipoprotein receptor-related protein 2 precursor

    See identical proteins and their annotated locations for NP_004516.2

    Status: REVIEWED

    Source sequence(s)
    AC007556, AY265357, AY265358, CD673312, DA200673, DA339827, DA401915, U33837
    Consensus CDS
    CCDS2232.1
    UniProtKB/Swiss-Prot
    P98164
    UniProtKB/TrEMBL
    Q7Z5C0, Q7Z5C1
    Related
    ENSP00000263816.3, OTTHUMP00000163042, ENST00000263816.7, OTTHUMT00000255231
    Conserved Domains (12) summary
    smart00192
    Location:29052937
    LDLa; Low-density lipoprotein receptor domain class A
    smart00135
    Location:15011543
    LY; Low-density lipoprotein-receptor YWTD domain
    smart00179
    Location:40074047
    EGF_CA; Calcium-binding EGF-like domain
    COG3391
    Location:20922285
    YncE; DNA-binding beta-propeller fold protein YncE [General function prediction only]
    cd00112
    Location:37593793
    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 ...
    cd05819
    Location:20972142
    NHL; NHL repeat [structural motif]
    pfam00057
    Location:28632895
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00058
    Location:41974237
    Ldl_recept_b; Low-density lipoprotein receptor repeat class B
    pfam12662
    Location:31323155
    cEGF; Complement Clr-like EGF-like
    pfam14670
    Location:23462382
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:31473190
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
    cl18310
    Location:20912300
    NHL; NHL repeat unit of beta-propeller proteins

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    169127109..169362612 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011511183.3XP_011509485.1  low-density lipoprotein receptor-related protein 2 isoform X1

    Conserved Domains (12) summary
    smart00192
    Location:29052937
    LDLa; Low-density lipoprotein receptor domain class A
    smart00135
    Location:15011543
    LY; Low-density lipoprotein-receptor YWTD domain
    smart00179
    Location:39644004
    EGF_CA; Calcium-binding EGF-like domain
    COG3391
    Location:20922285
    YncE; DNA-binding beta-propeller fold protein YncE [General function prediction only]
    cd00112
    Location:37163750
    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 ...
    cd05819
    Location:20972142
    NHL; NHL repeat [structural motif]
    pfam00057
    Location:28632895
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00058
    Location:41544194
    Ldl_recept_b; Low-density lipoprotein receptor repeat class B
    pfam12662
    Location:31323155
    cEGF; Complement Clr-like EGF-like
    pfam14670
    Location:23462382
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:31473190
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
    cl18310
    Location:20912300
    NHL; NHL repeat unit of beta-propeller proteins
  2. XM_011511184.2XP_011509486.1  low-density lipoprotein receptor-related protein 2 isoform X2

    Conserved Domains (12) summary
    smart00192
    Location:21422174
    LDLa; Low-density lipoprotein receptor domain class A
    smart00135
    Location:738780
    LY; Low-density lipoprotein-receptor YWTD domain
    smart00179
    Location:32443284
    EGF_CA; Calcium-binding EGF-like domain
    COG3391
    Location:13291522
    YncE; DNA-binding beta-propeller fold protein YncE [General function prediction only]
    cd00112
    Location:29963030
    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 ...
    cd05819
    Location:13341379
    NHL; NHL repeat [structural motif]
    pfam00057
    Location:21002132
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00058
    Location:34343474
    Ldl_recept_b; Low-density lipoprotein receptor repeat class B
    pfam12662
    Location:23692392
    cEGF; Complement Clr-like EGF-like
    pfam14670
    Location:15831619
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:23842427
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
    cl18310
    Location:13281537
    NHL; NHL repeat unit of beta-propeller proteins
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