Manf
Developmental stage
Expressed from birth.
Domain
The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response.
Function
Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells. 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.
Sequence Similarities
Belongs to the ARMET family.
Tissue Specificity
Strongly expressed in pancreatic islets and spermatocytes (at protein level). Expressed in chondrocytes (at protein level) (PubMed:23956175).
Cellular localization
- Secreted
- Endoplasmic reticulum lumen
- Sarcoplasmic reticulum lumen
- Retained in the endoplasmic reticulum (ER), and sarcoplasmic reticulum (SR) under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia.
Alternative names
Armet, Manf, Mesencephalic astrocyte-derived neurotrophic factor, Arginine-rich protein, Protein ARMET