M6PR | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | M6PR , CD-MPR, MPR 46, MPR-46, MPR46, SMPR, CD-mannose-6-phosphate receptor, cation dependent | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 154540 MGI: 96904 HomoloGene: 31086 GeneCards: M6PR | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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In the fields of biochemistry and cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein that in humans is encoded by the M6PR gene. [5] [6]
The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate (M6P) tags on acid hydrolase precursors in the Golgi apparatus that are destined for transport to the lysosome. Homologues of CD-MPR are found in all eukaryotes.
The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail. [7] The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer.
The cell surface receptor for insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor. [7] It consists of fifteen repeats homologous to the 157-residue CD-M6PR domain, two of which are responsible for binding to M6P.
Both CD-MPRs and CI-MPRs are lectins that bind their M6P-tagged cargo in the lumen of the Golgi apparatus. The CD-MPR shows greatly enhanced binding to M6P in the presence of divalent cations, such as manganese. [7] The MPRs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles. [8] They are trafficked to the early endosome where, in the relatively low pH environment of the endosome, the MPRs release their cargo. The MPRs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the MPRs.
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 materials. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.
A lysosome is a single membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that digest many kinds of biomolecules. A lysosome has a specific composition, of both its membrane proteins and its lumenal proteins. The lumen's pH (~4.5–5.0) is optimal for the enzymes involved in hydrolysis, analogous to the activity of the stomach. Besides degradation of polymers, the lysosome is involved in cell processes of secretion, plasma membrane repair, apoptosis, cell signaling, and energy metabolism.
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus.
Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network (TGN) and directly back to the plasma membrane. Mutations in retromer and its associated proteins have been linked to Alzheimer's and Parkinson's diseases.
Sorting nexin-1 is a protein that in humans is encoded by the SNX1 gene. The protein encoded by this gene is a sorting nexin. SNX1 is a component of the retromer complex.
Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.
Mannose-6-phosphate (M6P) is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase.
The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates.
ADP-ribosylation factor-binding protein GGA1 is a protein that in humans is encoded by the GGA1 gene.
ADP-ribosylation factor-binding protein GGA3 is a protein that in humans is encoded by the GGA3 gene.
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.
ADP-ribosylation factor-binding protein GGA2 is a protein that in humans is encoded by the GGA2 gene.
Mannose-6-phosphate receptor binding protein 1 (M6PRBP1) is a protein which in humans is encoded by the M6PRBP1 gene. Its gene product, as well as the gene itself, is commonly known as TIP47.
Alpha-centractin (yeast) or ARP1 is a protein that in humans is encoded by the ACTR1A gene.
VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex.
Rab GTPase-binding effector protein 1 is an enzyme that in humans is encoded by the RABEP1 gene. It belongs to rabaptin protein family.
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase is an enzyme that in humans is encoded by the NAGPA gene.
Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.
Rab9 effector protein with Kelch motifs also known as p40 is a protein that in humans is encoded by the RABEPK gene.
The endosomal sorting complexes required for transport (ESCRT) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans. A eukaryotic signature protein, the machinery is found in all eukaryotes and some archaea.