Mouse Anti-PRNP Recombinant Antibody (8H4) (CBMAB-0715CQ)

Prion protein

The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that tends to aggregate into rod-like structures. The encoded protein contains a highly unstable region of five tandem octapeptide repeats. This gene is found on chromosome 20, approximately 20 kbp upstream of a gene which encodes a biochemically and structurally similar protein to the one encoded by this gene. Mutations in the repeat region as well as elsewhere in this gene have been associated with Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru. An overlapping open reading frame has been found for this gene that encodes a smaller, structurally unrelated protein, AltPrp. Alternative splicing results in multiple transcript variants.

CJD; GSS; PrP; ASCR; KURU; PRIP; PrPc; CD230; AltPrP; p27-30; PrP27-30; PrP33-35C

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 Cu2+ or Zn2+ for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).

Activation of protein kinase activityIEA:Ensembl
Calcium-mediated signaling using intracellular calcium sourceManual Assertion Based On ExperimentIGI:ARUK-UCL
Cell cycleIEA:UniProtKB-KW
Cellular copper ion homeostasis1 PublicationNAS:UniProtKB
Cellular response to amyloid-betaManual Assertion Based On ExperimentIGI:ARUK-UCL
Cellular response to copper ionManual Assertion Based On ExperimentIDA:MGI
Cellular response to xenobiotic stimulusIEA:Ensembl
Dendritic spine maintenanceManual Assertion Based On ExperimentTAS:ARUK-UCL
Learning or memoryISS:ARUK-UCL
Long-term memoryManual Assertion Based On ExperimentTAS:ARUK-UCL
Negative regulation of activated T cell proliferationISS:BHF-UCL
Negative regulation of amyloid precursor protein catabolic processISS:ARUK-UCL
Negative regulation of amyloid-beta formationISS:ARUK-UCL
Negative regulation of apoptotic processIEA:Ensembl
Negative regulation of calcineurin-NFAT signaling cascadeISS:BHF-UCL
Negative regulation of dendritic spine maintenanceISS:ARUK-UCL
Negative regulation of DNA-binding transcription factor activityISS:BHF-UCL
Negative regulation of interferon-gamma productionISS:BHF-UCL
Negative regulation of interleukin-17 productionISS:BHF-UCL
Negative regulation of interleukin-2 productionISS:BHF-UCL
Negative regulation of long-term synaptic potentiationIEA:Ensembl
Negative regulation of protein phosphorylationISS:BHF-UCL
Negative regulation of protein processingManual Assertion Based On ExperimentTAS:ARUK-UCL
Negative regulation of T cell receptor signaling pathwayISS:BHF-UCL
Neuron projection maintenanceISS:ARUK-UCL
Positive regulation of neuron apoptotic processManual Assertion Based On ExperimentIMP:CAFA
Positive regulation of neuron deathISS:ARUK-UCL
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of protein localization to plasma membraneIEA:Ensembl
Positive regulation of protein targeting to membraneISS:ARUK-UCL
Positive regulation of protein tyrosine kinase activityManual Assertion Based On ExperimentIGI:ARUK-UCL
Protein destabilizationManual Assertion Based On ExperimentIMP:CAFA
Protein homooligomerizationIEA:InterPro
Regulation of calcium ion import across plasma membraneISS:ARUK-UCL
Biological Process regulation of glutamate receptor signaling pathwayISS:ARUK-UCL
Biological Process regulation of intracellular calcium activated chloride channel activityManual Assertion Based On ExperimentIGI:ARUK-UCL
Regulation of peptidyl-tyrosine phosphorylationISS:ARUK-UCL
Regulation of potassium ion transmembrane transportIEA:Ensembl
Response to amyloid-betaISS:ARUK-UCL
Response to cadmium ionIEA:Ensembl
Response to oxidative stressISS:UniProtKB

Cell membrane
Golgi apparatus
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.

Creutzfeldt-Jakob disease (CJD):
Occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.
Fatal familial insomnia (FFI):
Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.
Gerstmann-Straussler disease (GSD):
A rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain. GSD presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years.
Huntington disease-like 1 (HDL1):
Autosomal dominant, early-onset neurodegenerative disorder with prominent psychiatric features.
Kuru (KURU):
Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset.
Spongiform encephalopathy with neuropsychiatric features (SENF):
Autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.

The glycosylation pattern (the amount of mono-, di- and non-glycosylated forms or glycoforms) seems to differ in normal and CJD prion.