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Low density lipoprotein receptor-related protein 2 also known as LRP-2 or megalin is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''LRP2''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.


Function

LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman nephritis) and originally named gp330 and subsequently megalin and later LRP2. LRP2/megalin is a multiligand binding
receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
found in the
plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
of many absorptive epithelial
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s. LRP2/megalin is a member of a family of receptors with structural similarities to the low density lipoprotein receptor ( LDLR). LRP2/megalin functions to mediate
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
of ligands leading to degradation in lysosomes or transcytosis. LRP2/megalin can also form complexes with
cubilin Cubilin is a protein that in humans is encoded by the ''CUBN'' gene. Function Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a re ...
: those complexes are able to reabsorb several molecules and can be inhibited by sodium maleate. LRP2 is expressed in epithelial cells of the
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
(thyrocytes), where it can serve as a receptor for the protein
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment o ...
(Tg).


Clinical significance

Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.


Interactions

LRP2 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with: *
DAB2 Disabled homolog 2 is a protein that in humans is encoded by the ''DAB2'' gene. Function DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines. The 770-amino acid predicted ...
, *
DLG4 PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is encoded by the ''DLG4'' (discs large homolog 4) gene. PSD-95 is a member of the membrane-associated guanylate kinase (MAG ...
, *
GIPC1 GIPC PDZ domain containing family, member 1 (GIPC1) is a protein that in humans is encoded by the ''GIPC1'' gene. GIPC was originally identified as it binds specifically to the C terminus of RGS-GAIP, a protein involved in the regulation of G prot ...
, *
ITGB1BP1 Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ''ITGB1BP1'' gene. The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domai ...
, *
LDL-receptor-related protein associated protein Low density lipoprotein receptor-related protein-associated protein 1 also known as LRPAP1 or RAP is a chaperone protein which in humans is encoded by the LRPAP1 gene. Function LRPAP1 is involved with trafficking of certain members of the LD ...
, *
LDLRAP1 Low-density lipoprotein receptor adapter protein 1 is a protein that in humans is encoded by the ''LDLRAP1'' gene. The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTB) domain. The PTB domain has b ...
, *
MAGI1 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 is an enzyme that in humans is encoded by the ''MAGI1'' gene. Function The protein encoded by this gene is a member of the membrane-associated guanylate kinase homolog ...
, *
MAPK8IP1 C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the ''MAPK8IP1'' gene. The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein ...
, *
MAPK8IP2 C-jun-amino-terminal kinase-interacting protein 2 is a protein or the name of the gene that encodes it. The gene is also known as Islet-Brain-2 (IB2). This protein is highly expressed in the brain and is almost always deleted in Phelan-McDermid s ...
, *
NOS1AP Nitric oxide synthase 1 adaptor protein (NOS1AP) also known as carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) is a protein that in humans is encoded by the ''NOS1AP'' gene. This gene encodes a cytosolic protein tha ...
, and *
SYNJ2BP Synaptojanin-2-binding protein is a protein that in humans is encoded by the ''SYNJ2BP'' gene. Interactions SYNJ2BP has been shown to interact with: * ACVR2A, * ACVR2B, * LRP1, and * LRP2 Low density lipoprotein receptor-related protein 2 a ...
.


References


Further reading

* * * * * * * * * * * * * * * * * *


External links


GeneReviews/NCBI/NIH/UW entry on Donnai-Barrow Syndrome
{{Lipoprotein metabolism