P67994 · PRIO_MACFU
- ProteinMajor prion protein
- GenePRNP
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids253 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
function
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu2+ or Zn2+ for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 61 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 62 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 63 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 69 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 70 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 71 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 77 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 78 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 79 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 85 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 86 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 87 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | Golgi apparatus | |
Cellular Component | plasma membrane | |
Cellular Component | side of membrane | |
Molecular Function | copper ion binding | |
Biological Process | protein homooligomerization |
Keywords
- Molecular function
- Ligand
Names & Taxonomy
Protein names
- Recommended nameMajor prion protein
- Short namesPrP
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionP67994
- Secondary accessions
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor, GPI-anchor
Note: Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of Cu2+, to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis.
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, lipidation, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-22 | |||||
Sequence: MANLGCWMLVLFVATWSDLGLC | ||||||
Chain | PRO_0000025685 | 23-230 | Major prion protein | |||
Sequence: KKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGS | ||||||
Disulfide bond | 179↔214 | |||||
Sequence: CVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMC | ||||||
Glycosylation | 181 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 197 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Lipidation | 230 | GPI-anchor amidated serine | ||||
Sequence: S | ||||||
Propeptide | PRO_0000025686 | 231-253 | Removed in mature form | |||
Sequence: SMVLFSSPPVILLISFLIFLIVG |
Keywords
- PTM
PTM databases
Interaction
Subunit
Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on the path to fibril formation. Copper binding may promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement. Interacts with KIAA1191.
Structure
Family & Domains
Features
Showing features for region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 23-230 | Interaction with GRB2, ERI3 and SYN1 | ||||
Sequence: KKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGS | ||||||
Region | 26-108 | Disordered | ||||
Sequence: PKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTS | ||||||
Repeat | 51-59 | 1 | ||||
Sequence: PQGGGGWGQ | ||||||
Region | 51-91 | 5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q | ||||
Sequence: PQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQ | ||||||
Repeat | 60-67 | 2 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 68-75 | 3 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 76-83 | 4 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 84-91 | 5 | ||||
Sequence: PHGGGWGQ |
Domain
The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization.
Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization.
Sequence similarities
Belongs to the prion family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length253
- Mass (Da)27,676
- Last updated2004-10-11 v1
- ChecksumF01D5EA64AB68C31