MANF - mesencephalic astrocyte derived neurotrophic factor (human)
Gene
Symbol
Taxonomy
Dates
- Create:2016-09-14
- Modify:2025-01-18
Description
The protein encoded by the MANF gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]
Enables sulfatide binding activity. Involved in regulation of response to endoplasmic reticulum stress. Located in endoplasmic reticulum lumen. Implicated in Parkinsonism; breast cancer; carcinoma (multiple); and pancreatic cancer.
- ARMET
- ARP
- DDDS
- mesencephalic astrocyte-derived neurotrophic factor
- arginine-rich, mutated in early stage tumors
Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PMID: 12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (PMID: 18561914, PMID: 22637475, PMID: 29497057). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PMID: 22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PMID: 22637475). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PMID: 29497057). Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions (PMID: 29497057).
Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605
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