MANF

The protein encoded by this 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.

MESENCEPHALIC ASTROCYTE DERIVED NEUROTROPHIC FACTOR

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed: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 (PubMed:18561914, PubMed:22637475, PubMed:29497057).
Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PubMed:22637475).
Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475).
Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PubMed: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 (PubMed:29497057).

Dopaminergic neuron differentiationManual Assertion Based On ExperimentIBA:GO_Central
Neuron projection developmentManual Assertion Based On ExperimentIBA:GO_Central
Regulation of response to endoplasmic reticulum stressManual Assertion Based On ExperimentIMP:UniProtKB
Response to unfolded proteinIEA:UniProtKB-KW

Secreted
Endoplasmic reticulum lumen
Sarcoplasmic reticulum lumen
Retained in the endoplasmic reticulum (ER), and sarcoplasmic reticulum (SR) under normal conditions (PubMed:22637475).
Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475, PubMed:29497057).

May contain sialic acid residues.