UniProt functional annotation for P23907



	UniProt functional annotation for P23907

UniProt code: P23907.

Organism: Ovis aries (Sheep).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Caprinae; Ovis.

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 Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity). {ECO:0000250|UniProtKB:P04156, ECO:0000250|UniProtKB:P04925}.

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. {ECO:0000250|UniProtKB:P04156, ECO:0000250|UniProtKB:P04925}.

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}.

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. {ECO:0000250|UniProtKB:P04156}.

Domain: 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. {ECO:0000250|UniProtKB:P04156}.

Polymorphism: A number of amino acid polymorphism sites that influence scrapie susceptibility and transmission have been described. These are alanine to threonine or valine at codon 136, arginine to histidine at codon 154, and arginine to glutamine, histidine or lysine at codon 171. A number of allelic variants have been described based on the amino acids found at these three positions: VRQ, ARQ, AHQ, TRQ, ARK, ARR and ARH. {ECO:0000269|PubMed:14769911}.

Disease: Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc. {ECO:0000305}.

Disease: Note=Scrapie is a transmissible neurodegenerative disorder of sheep and goats. Most sheep that contract the disease naturally die between 24 and 50 months of age. The incubation period in sheep depends on the strain(s) of the infecting pathogen, sheep age at exposure, and the sheep genotype. Scrapie can be spread between flockmates, or it can be transmitted from an infected ewe to its lamb. {ECO:0000269|PubMed:1681027, ECO:0000269|PubMed:7897344, ECO:0000269|PubMed:8094373}.

Miscellaneous: This protein is produced by a bicistronic gene which also produces the major prion protein/PRNP from an overlapping reading frame.

Miscellaneous: The alternative prion protein/AltPrP (AC F7VJQ3) and PRNP have no apparent direct functional relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of PRNP (By similarity). In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon. {ECO:0000250}.

Similarity: Belongs to the prion family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Ovis aries (Sheep).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Caprinae; Ovis.



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 Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity). {ECO:0000250\|UniProtKB:P04156, ECO:0000250\|UniProtKB:P04925}.


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. {ECO:0000250\|UniProtKB:P04156, ECO:0000250\|UniProtKB:P04925}.
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}.
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. {ECO:0000250\|UniProtKB:P04156}.
Domain:		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. {ECO:0000250\|UniProtKB:P04156}.
Polymorphism:		A number of amino acid polymorphism sites that influence scrapie susceptibility and transmission have been described. These are alanine to threonine or valine at codon 136, arginine to histidine at codon 154, and arginine to glutamine, histidine or lysine at codon 171. A number of allelic variants have been described based on the amino acids found at these three positions: VRQ, ARQ, AHQ, TRQ, ARK, ARR and ARH. {ECO:0000269\|PubMed:14769911}.
Disease:		Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc. {ECO:0000305}.
Disease:		Note=Scrapie is a transmissible neurodegenerative disorder of sheep and goats. Most sheep that contract the disease naturally die between 24 and 50 months of age. The incubation period in sheep depends on the strain(s) of the infecting pathogen, sheep age at exposure, and the sheep genotype. Scrapie can be spread between flockmates, or it can be transmitted from an infected ewe to its lamb. {ECO:0000269\|PubMed:1681027, ECO:0000269\|PubMed:7897344, ECO:0000269\|PubMed:8094373}.
Miscellaneous:		This protein is produced by a bicistronic gene which also produces the major prion protein/PRNP from an overlapping reading frame.
Miscellaneous:		The alternative prion protein/AltPrP (AC F7VJQ3) and PRNP have no apparent direct functional relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of PRNP (By similarity). In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon. {ECO:0000250}.
Similarity:		Belongs to the prion family. {ECO:0000305}.