PRNP
Major prion protein
Also known as: AltPrP, CD230, CJD, GSS, PRIO_HUMAN, PRIP, PRP
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P04156
- Gene
- PRNP
- Ensembl
- ENSG00000171867
- Chromosome
- 20
- Canonical length
- 253 aa
- Protein class
- CD markers, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted membrane proteins, Transporters
- Subcellular location
- Nuclear membrane,Vesicles,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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. [provided by RefSeq, Nov 2014]
Canonical amino-acid sequenceUniProt
253 residues, UniProt reviewed canonical sequence.
>P04156|PRNP
1 MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGGGWGQP
61 HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HMAGAAAAGA
121 VVGGLGGYML GSAMSRPIIH FGSDYEDRYY RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV
181 NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV
241 ILLISFLIFL IVGLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PRNP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.52
- Highest tissue expression
- 480 nTPM
Expression across tissuesHPA
Tissue
- choroid plexus: 480 nTPM
- cerebral cortex: 367 nTPM
- cerebellum: 290 nTPM
- basal ganglia: 233 nTPM
- hippocampal formation: 223 nTPM
- amygdala: 219 nTPM
Single-cell type
- ocular epithelial cells: 461 nCPM
- kupffer cells: 448 nCPM
- epididymal basal cells: 384 nCPM
- retinal pigment epithelial cells: 379 nCPM
- schwann cells: 369 nCPM
- basal keratinocytes: 343 nCPM
Immune cell
- basophil: 880 nTPM
- MAIT T-cell: 101 nTPM
- classical monocyte: 74 nTPM
- T-reg: 73 nTPM
- total PBMC: 73 nTPM
- gdT-cell: 67 nTPM
Brain region
- choroid plexus: 609 nTPM
- cerebral cortex: 403 nTPM
- basal ganglia: 367 nTPM
- thalamus: 364 nTPM
- white matter: 332 nTPM
- hippocampal formation: 328 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about PRNP.
Disease | AllUniProt
Conditions PRNP is implicated in, by any mechanism.
- Creutzfeldt-Jakob disease (CJD) MIM:123400
- Fatal familial insomnia (FFI) MIM:600072
- Gerstmann-Straussler disease (GSD) MIM:137440
- Huntington disease-like 1 (HDL1) MIM:603218
- Kuru (KURU) MIM:245300
- Spongiform encephalopathy with neuropsychiatric features (SENF) MIM:606688
Disease | GeneticClinVar
29 pathogenic / likely-pathogenic of 197 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Huntington disease-like 1
- Gerstmann-Straussler-Scheinker syndrome
- Inherited Creutzfeldt-Jakob disease
- Spongiform encephalopathy with neuropsychiatric features
- CEREBRAL AMYLOID ANGIOPATHY, PRNP-RELATED
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.3
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.18
- DepMap mean gene effect
- 0.09
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to amyloid-beta
- cellular response to copper ion
- cellular response to xenobiotic stimulus
- dendritic spine maintenance
- intracellular copper ion homeostasis
- intracellular signal transduction
- learning or memory
- long-term memory
- 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 interleukin-17 production
- negative regulation of interleukin-2 production
- negative regulation of long-term synaptic potentiation
- negative regulation of protein processing
- negative regulation of T cell receptor signaling pathway
- negative regulation of transcription by RNA polymerase II
- negative regulation of type II interferon production
- neuron projection maintenance
- positive regulation of calcium-mediated signaling
- positive regulation of glutamate receptor signaling pathway
- positive regulation of neuron apoptotic process
- positive regulation of protein localization to plasma membrane
- positive regulation of protein targeting to membrane
- protein destabilization
- protein homooligomerization
- regulation of calcium ion import across plasma membrane
- regulation of cell cycle
- regulation of glutamate receptor signaling pathway
- regulation of potassium ion transmembrane transport
- response to amyloid-beta
- response to cadmium ion
- response to oxidative stress
Molecular functions
- amyloid-beta binding
- aspartic-type endopeptidase inhibitor activity
- ATP-dependent protein binding
- copper ion binding
- cupric ion binding
- cuprous ion binding
- glycosaminoglycan binding
- identical protein binding
- lamin binding
- microtubule binding
- molecular adaptor activity
- molecular condensate scaffold activity
- molecular function activator activity
- protease binding
- protein-containing complex binding
- protein-folding chaperone binding
- signaling receptor activity
- transmembrane transporter binding
- tubulin binding
- type 5 metabotropic glutamate receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Prion/Doppel protein, beta-ribbon domain
- Prion/Doppel beta-ribbon domain superfamily
- Prion/Doppel alpha-helical domain
- Prion protein
- Prion, copper binding octapeptide repeat region
- Major prion protein N-terminal
- Copper binding octapeptide repeat region
- Major prion protein bPrPp - N terminal
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PRNP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PRNP as an antibody target. Whether an autoantibody or antibody against PRNP could matter depends on whether native PRNP is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PRNP is annotated at the cell surface, where native PRNP is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label PRNP as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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