Protein: Major prion protein (PrP) (CD antigen CD230) (P13852)
Organism: Rattus norvegicus (Rat)
Function: Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P04156}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P04156}. Golgi apparatus {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of Cu(2+), to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis. {ECO:0000250|UniProtKB:P04156}.
Sequence: MANLGYWLLALFVTTCTDVGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQSGGTWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWSQGGGTHNQWNKPSKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPMLHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYYDGRRSSAVLFSSPPVILLISFLIFLIVG
InterPro domains: - IPR020949: Prion, copper binding octapeptide repeat region (repeat) [50-95]
- IPR000817: Prion protein (family) [7-252]
- IPR036924: Prion/Doppel beta-ribbon domain superfamily (homologous_superfamily) [90-231]
- IPR022416: Prion/Doppel protein, beta-ribbon domain (domain) [113-252]
- IPR025860: Major prion protein N-terminal (domain) [1-28]
Interaction partners: - Neural cell adhesion molecule 1
- Stress-induced-phosphoprotein 1
- Amyloid-beta precursor protein
- Tyrosine-protein kinase Fyn
- Neural cell adhesion molecule 2
- Ig-like domain-containing protein
- Caveolin-1
- Alpha-synuclein
- Endoplasmic reticulum chaperone BiP
- Glycogen synthase kinase-3 beta
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0042802 (identical protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0071840 (cellular component organization or biogenesis), GO:0003008 (system process), GO:0009892 (negative regulation of metabolic process), GO:0065008 (regulation of biological quality), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0007610 (behavior), GO:0048522 (positive regulation of cellular process), GO:0050790 (regulation of catalytic activity), GO:0010942 (positive regulation of cell death), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044093 (positive regulation of molecular function), GO:0051049 (regulation of transport), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0032409 (regulation of transporter activity), GO:0034762 (regulation of transmembrane transport), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0031647 (regulation of protein stability), GO:0010033 (response to organic substance), GO:0010035 (response to inorganic substance), GO:0010941 (regulation of cell death), GO:1901698 (response to nitrogen compound), GO:0031325 (positive regulation of cellular metabolic process), GO:0007611 (learning or memory), GO:0070887 (cellular response to chemical stimulus), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0050877 (nervous system process), GO:0080090 (regulation of primary metabolic process), GO:1901216 (positive regulation of neuron death), GO:0010038 (response to metal ion), GO:0071417 (cellular response to organonitrogen compound), GO:1901652 (response to peptide), GO:0050890 (cognition), GO:0030030 (cell projection organization), GO:0010562 (positive regulation of phosphorus metabolic process), GO:0051246 (regulation of protein metabolic process), GO:0071310 (cellular response to organic substance), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death), GO:0034765 (regulation of monoatomic ion transmembrane transport), GO:0051248 (negative regulation of protein metabolic process), GO:0043954 (cellular component maintenance), GO:1901699 (cellular response to nitrogen compound), GO:1901214 (regulation of neuron death), GO:0010468 (regulation of gene expression), GO:0019932 (second-messenger-mediated signaling), GO:0007613 (memory), GO:0010243 (response to organonitrogen compound), GO:0071241 (cellular response to inorganic substance), GO:0051247 (positive regulation of protein metabolic process), GO:0022898 (regulation of transmembrane transporter activity), GO:0051338 (regulation of transferase activity), GO:0099173 (postsynapse organization), GO:0043269 (regulation of monoatomic ion transport), GO:0043085 (positive regulation of catalytic activity), GO:0031648 (protein destabilization), GO:0034330 (cell junction organization), GO:1901701 (cellular response to oxygen-containing compound), GO:0010629 (negative regulation of gene expression), GO:0051174 (regulation of phosphorus metabolic process), GO:0043065 (positive regulation of apoptotic process), GO:0042981 (regulation of apoptotic process), GO:0051347 (positive regulation of transferase activity), GO:0030162 (regulation of proteolysis), GO:0044070 (regulation of monoatomic anion transport), GO:0031399 (regulation of protein modification process), GO:0045937 (positive regulation of phosphate metabolic process), GO:0032412 (regulation of monoatomic ion transmembrane transporter activity), GO:0120036 (plasma membrane bounded cell projection organization), GO:0043523 (regulation of neuron apoptotic process), GO:0019722 (calcium-mediated signaling), GO:0019220 (regulation of phosphate metabolic process), GO:1903318 (negative regulation of protein maturation), GO:0071248 (cellular response to metal ion), GO:0043549 (regulation of kinase activity), GO:1901653 (cellular response to peptide), GO:1904645 (response to amyloid-beta), GO:0097061 (dendritic spine organization), GO:0046688 (response to copper ion), GO:0007616 (long-term memory), GO:0050808 (synapse organization), GO:1903959 (regulation of monoatomic anion transmembrane transport), GO:0045861 (negative regulation of proteolysis), GO:1903317 (regulation of protein maturation), GO:0031401 (positive regulation of protein modification process), GO:0043525 (positive regulation of neuron apoptotic process), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:1904646 (cellular response to amyloid-beta), GO:0033674 (positive regulation of kinase activity), GO:0010359 (regulation of anion channel activity), GO:0010955 (negative regulation of protein processing), GO:0045859 (regulation of protein kinase activity), GO:0070613 (regulation of protein processing), GO:0071280 (cellular response to copper ion), GO:0106027 (neuron projection organization), GO:0042327 (positive regulation of phosphorylation), GO:0001934 (positive regulation of protein phosphorylation), GO:0035584 (calcium-mediated signaling using intracellular calcium source), GO:0050731 (positive regulation of peptidyl-tyrosine phosphorylation), GO:0061097 (regulation of protein tyrosine kinase activity), GO:0050730 (regulation of peptidyl-tyrosine phosphorylation), GO:0045860 (positive regulation of protein kinase activity), GO:0061098 (positive regulation of protein tyrosine kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0044297 (cell body), GO:0009986 (cell surface), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0031975 (envelope), GO:0098794 (postsynapse), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0120025 (plasma membrane bounded cell projection), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0045211 (postsynaptic membrane), GO:0043025 (neuronal cell body), GO:0005794 (Golgi apparatus), GO:0043197 (dendritic spine), GO:0098590 (plasma membrane region), GO:0005783 (endoplasmic reticulum), GO:0005635 (nuclear envelope), GO:0097447 (dendritic tree), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0099572 (postsynaptic specialization), GO:0097060 (synaptic membrane), GO:0031965 (nuclear membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0014069 (postsynaptic density), GO:0030425 (dendrite), GO:0043005 (neuron projection), GO:0098984 (neuron to neuron synapse), GO:0000139 (Golgi membrane), GO:0032279 (asymmetric synapse), GO:0005634 (nucleus), GO:0044309 (neuron spine)