Mesencephalic astrocyte-derived neurotrophic factor (P0C5H9)

Uniprot ID P0C5H9
Protein Name Mesencephalic astrocyte-derived neurotrophic factor
Gene Name Manf
Species Rattus norvegicus (Rat)
Signal peptide(a) Y Secretome P(b)
Function Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (By similarity). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (PubMed:16462600). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (PubMed:16462600). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (By similarity). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (By similarity). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (By similarity). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (By similarity). 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 (By similarity). .
GO - Molecular function
  • growth factor activity : IEA:UniProtKB-KW
  • sulfatide binding : ISO:RGD
GO - Biological process
  • dopaminergic neuron differentiation : IBA:GO_Central
  • neuron projection development : IBA:GO_Central
  • regulation of response to endoplasmic reticulum stress : ISO:RGD
  • response to unfolded protein : IEA:UniProtKB-KW
  • vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure : ISO:RGD
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(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.