Protein: Mesencephalic astrocyte-derived neurotrophic factor (Arginine-rich protein) (Protein ARMET) (Q9CXI5)
Organism: Mus musculus (Mouse)
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.
Subcellular location: Secreted {ECO:0000269|PubMed:17507765, ECO:0000269|PubMed:23956175}. Endoplasmic reticulum lumen {ECO:0000269|PubMed:23956175}. Sarcoplasmic reticulum lumen {ECO:0000250|UniProtKB:P55145}. Note=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. {ECO:0000250|UniProtKB:P55145}.
Sequence: MWATRGLAVALALSVLPDSRALRPGDCEVCISYLGRFYQDLKDRDVTFSPATIEEELIKFCREARGKENRLCYYIGATDDAATKIINEVSKPLAHHIPVEKICEKLKKKDSQICELKYDKQIDLSTVDLKKLRVKELKKILDDWGEMCKGCAEKSDYIRKINELMPKYAPKAASARTDL
InterPro domains: - IPR019345: ARMET, C-terminal (domain) [126-168]
- IPR045332: ARMET, N-terminal (domain) [26-122]
- IPR036361: SAP domain superfamily (homologous_superfamily) [123-179]
- IPR045333: ARMET-like (family) [1-179]
Interaction partners: - Endoplasmic reticulum chaperone BiP
- Protein disulfide isomerase Creld2
- DnaJ homolog subfamily B member 11
- Stromal cell-derived factor 2-like protein 1
- X-box-binding protein 1
- Ubiquitin-conjugating enzyme E2 N
- Endoplasmin
- Protein disulfide-isomerase A4
- Proactivator polypeptide-like 1
- Protein disulfide-isomerase A6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097367 (carbohydrate derivative binding), GO:0008289 (lipid binding), GO:0051861 (glycolipid binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0048583 (regulation of response to stimulus), GO:0050794 (regulation of cellular process), GO:0080135 (regulation of cellular response to stress), GO:0080134 (regulation of response to stress), GO:1905897 (regulation of response to endoplasmic reticulum stress)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)