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

    Gene ID: 4036, updated on 24-Dec-2017
    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
    Location:
    2q31.1
    Exon count:
    80
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (169127109..169362613, 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

    • 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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
    • 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...
    Products Interactant Other Gene Complex Source Pubs Description

    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 
    drug binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    lipoprotein transporter activity TAS
    Traceable Author Statement
    more info
     
    low-density lipoprotein 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 
    folic acid 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 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
     
    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 
    Preferred Names
    low-density lipoprotein receptor-related protein 2
    Names
    Heymann nephritis antigen homolog
    LRP-2
    calcium sensor protein
    glycoprotein 330
    megalin

    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 108

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

      Range
      169127109..169362613 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011511183.2XP_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

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      169989632..170225372 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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