Major prion protein (PRNP)
The protein contains 253 amino acids for an estimated molecular weight of 27661 Da.
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). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
Biological Process
Activation of protein kinase activity
Calcium-mediated signaling using intracellular calcium source
Cell cycle arrest
Cellular copper ion homeostasis
Cellular response to amyloid-beta
Cellular response to copper ion
Cellular response to drug
Dendritic spine maintenance
Learning or memory
Long-term memory
Modulation of age-related behavioral decline
Negative regulation of activated T cell proliferation
Negative regulation of amyloid precursor protein catabolic process
Negative regulation of amyloid-beta formation
Negative regulation of apoptotic process
Negative regulation of calcineurin-NFAT signaling cascade
Negative regulation of dendritic spine maintenance
Negative regulation of DNA-binding transcription factor activity
Negative regulation of interferon-gamma production
Negative regulation of interleukin-17 production
Negative regulation of interleukin-2 production
Negative regulation of long-term synaptic potentiation
Negative regulation of protein phosphorylation
Negative regulation of protein processing
Negative regulation of T cell receptor signaling pathway
Neuron projection maintenance
Positive regulation of neuron apoptotic process
Positive regulation of neuron death
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of protein localization to plasma membrane
Positive regulation of protein targeting to membrane
Positive regulation of protein tyrosine kinase activity
Protein destabilization
Protein homooligomerization
Protein insertion into ER membrane
Regulation of calcium ion import across plasma membrane
Regulation of glutamate receptor signaling pathway
Regulation of intracellular calcium activated chloride channel activity
Regulation of peptidyl-tyrosine phosphorylation
Regulation of potassium ion transmembrane transport
Response to amyloid-beta
Response to cadmium ion
Response to oxidative stress
Cellular Component
Anchored component of external side of plasma membrane
Cell surface
Cytoplasm
Cytosol
Dendrite
Endoplasmic reticulum
Extracellular exosome
Extrinsic component of membrane
Golgi apparatus
Inclusion body
Intracellular membrane-bounded organelle
Membrane raft
Nuclear membrane
Nucleus
Obsolete cell
Plasma membrane
Postsynapse
Postsynaptic density
Terminal bouton
Molecular Function
Amyloid-beta binding
Aspartic-type endopeptidase inhibitor activity
ATP-dependent protein binding
Calcium ion binding
Chaperone binding
Copper ion binding
Cupric ion binding
Cuprous ion binding
Glycosaminoglycan binding
Identical protein binding
Ion channel binding
Lamin binding
Microtubule binding
Protease binding
Protein-containing complex binding
Signaling receptor activity
Tubulin binding
Type 5 metabotropic glutamate receptor binding
The reference OMIM entry for this protein is 123400
Creutzfeldt-jakob disease; cjd
Creutzfeldt-jakob disease, familial creutzfeldt-jakob disease, sporadic, included; scjd, included
Creutzfeldt-jakob disease, variant, included; vcjd, included
Creutzfeldt-jakob disease, heidenhain variant, include
A number sign (#) is used with this entry because familial Creutzfeldt-Jakob disease can be caused by mutation in the prion protein gene (PRNP; 176640). Gerstmann-Straussler disease (GSD; 137440) and familial fatal insomnia (FFI; 600072) are 2 other allelic inherited prion diseases caused by mutation in the PRNP gene.
DESCRIPTION
The human prion diseases occur in inherited, acquired, and sporadic forms. Approximately 15% are inherited and associated with coding mutations in the PRNP gene. Acquired prion diseases include iatrogenic CJD, kuru (245300), variant CJD (vCJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) in cattle. Variant CJD is believed to be acquired from cattle infected with BSE. However, the majority of human cases of prion disease occur as sporadic CJD (sCJD) (Collinge et al., 1996; Parchi et al., 2000; Hill et al., 2003). Johnson and Gibbs (1998) provided a comprehensive review of Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. Tyler (2003) described the characteristics of sporadic CJD as encapsulated by C. Miller Fisher in 1960.CLINICAL FEATURES
Jakob et al. (1950) gave a follow-up on the first reported family, in which members of 3 generations may have been affected. Male-to-male transmission was documented. Davidson and Rabiner (1940) described 3 affected sibs. Friede and Dejong (1964) and later May et al. (1968) described an affected father and 3 daughters. Onset was between 38 and 45 years with a short duration of 10 months to 2 years. The disorder began with forgetfulness and nervousness, and progressed to jerky, trembling movements of the hands, loss of facial expression, and unsteady gait. Pathologic findings included severe status spongiosus, diffuse nerve cell degeneration, and some glial proliferation. Rosenthal et al. (1976) reported a family in which 16 members had a neurologic disease ranging from subacute and chronic dementia to various motor system abnormalities without dementia. Inheritance was autosomal dominant. Although the proband had typical CJD with neuropathologic demonstration of spongiform encephalopathy, a first cousin had chronic dementia without spongiform changes. Both patients had PAS-positive, eosinophilic plaques throughout the brain. The authors suggested that susceptibility for neurologic disease in this family was inherited as an autosomal dominant trait. Buge et al. (1978) reported a family in which 8 members spanning 3 generations had CJD. The family originated from southeast England and settled in France in 1870. Cathala et al. (1980) identified a second affected branch of the family reported by Buge et al. (1978), bringing the total number of people affected to 14. The pattern of inheritance was clearly autosomal dominant. Bertoni et al. (1983) reported 7 individuals with CJD in 3 generations of a large kindred. They pointed out that 3 of 4 patients studied in detail were first observed with supranuclear gaze paralysis, gait ataxia, and rapidly progressive dementia. Most of the affected persons were farmers. In a Chilean family, Cartier et al. (1985) described a brother and sister and possibly a third sib who had an unusual form of Creutzfeldt-Jakob disease with prominent ataxia. Brown et al. (1984) found that 5 to 10% of CJD patients had a relatively long course lasting more than 2 years. Of this group, approximately 30% had familial disease. In addition, they had a younger age at onset (average, 48 ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 123400 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).