MANF
MANF (mesencephalic astrocyte derived neurotrophic factor, also known as ARP or ARMET) is an ER-resident protein that is also secreted. It promotes the survival of dopaminergic neurons and protects cells from endoplasmic reticulum stress-induced death. Browse Assay Genie's current range of MANF research reagents below, or read on for the biology behind the target.
MANF selectively promotes the survival of dopaminergic neurons of the ventral mid-brain and modulates GABAergic transmission to dopaminergic neurons of the substantia nigra, enhancing both spontaneous and evoked GABAergic inhibitory postsynaptic currents. Inside the cell, it is retained in the endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) through association with the chaperone HSPA5 (BiP). MANF stabilises HSPA5 in its substrate-bound ADP state and inhibits ATP binding and nucleotide exchange, which helps incorporate HSPA5 into chaperone-client complexes during ER stress. In this way it acts as a repressor of the unfolded protein response (UPR).
The protein is up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Once outside the cell, it binds the lipid sulfatide 3-O-sulfogalactosylceramide in the outer membrane of target cells. This binding promotes endocytic uptake and is required for MANF to relieve ER stress and cell toxicity under hypoxic and ER stress conditions. It also inhibits cell proliferation, and reducing expression of the MANF gene increases susceptibility to ER stress-induced death and results in cell proliferation. The protein belongs to the ARMET family and is found in the ER and Golgi as well as in secreted form.
Beyond the nervous system, MANF is essential for embryonic lung development and for the correct postnatal development of splenic white pulp. It is needed for endochondral ossification in long bones and the skull. In skeletal muscle it regulates the transition towards prorepair macrophages after injury, and in the myocardium it represses RELA expression and NF-kB signalling, limiting macrophage infiltration and M1 differentiation. The alias ARMET stems from the earlier name arginine-rich, mutated in early stage tumours. Polymorphisms in the N-terminal arginine-rich region were reported in solid tumours but were later found in normal tissues, so they are no longer thought to be tumour-related.
MANF promotes survival of ventral mid-brain dopaminergic neurons and modulates GABAergic input to the substantia nigra, making it a focus for dopaminergic neuron biology.
By binding HSPA5/BiP and repressing the unfolded protein response, MANF is a useful node for studying ER stress-induced cell death.
MANF is up-regulated and secreted in response to hypoxia and ER stress, and sulfatide-mediated uptake is needed for its protective role.
MANF regulates prorepair macrophage transition in injured muscle and limits NF-kB signalling and M1 macrophage differentiation in injured myocardium.
MANF promotes the survival of dopaminergic neurons and protects cells from ER stress-induced death. In the ER it binds HSPA5/BiP and represses the unfolded protein response. When secreted, it binds sulfatide on target cells and is taken up by endocytosis.
ARMET stands for arginine-rich, mutated in early stage tumours, an earlier name for the gene. Polymorphisms in its N-terminal arginine-rich region were reported in solid tumours but later found in normal tissue, so they are no longer considered tumour-related.
Yes. The human MANF gene has orthologues named Manf in both mouse and rat. Human MANF belongs to the ARMET family. Check the datasheet of any product for its validated reactivity.
Other ER chaperones, neurotrophic factors and NF-kB pathway targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P55145; product specifications from Assay Genie datasheets.