UniProtKB - P23907 (PRIO_SHEEP)
Major prion protein
PRNP
Functioni
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).
By similarityMiscellaneous
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 64 | Cu(2+) 1By similarity | 1 | |
Metal bindingi | 65 | Cu(2+) 1; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 66 | Cu(2+) 1; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 72 | Cu(2+) 2By similarity | 1 | |
Metal bindingi | 73 | Cu(2+) 2; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 74 | Cu(2+) 2; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 80 | Cu(2+) 3By similarity | 1 | |
Metal bindingi | 81 | Cu(2+) 3; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 82 | Cu(2+) 3; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 88 | Cu(2+) 4By similarity | 1 | |
Metal bindingi | 90 | Cu(2+) 4; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 91 | Cu(2+) 4; via amide nitrogen and carbonyl oxygenBy similarity | 1 |
GO - Molecular functioni
- amyloid-beta binding Source: Ensembl
- copper ion binding Source: UniProtKB
- cuprous ion binding Source: Ensembl
- identical protein binding Source: IntAct
- microtubule binding Source: AgBase
- protein-containing complex binding Source: Ensembl
- tubulin binding Source: AgBase
- type 5 metabotropic glutamate receptor binding Source: Ensembl
GO - Biological processi
- calcium-mediated signaling using intracellular calcium source Source: Ensembl
- cellular response to amyloid-beta Source: Ensembl
- cellular response to copper ion Source: Ensembl
- positive regulation of neuron apoptotic process Source: Ensembl
- positive regulation of protein tyrosine kinase activity Source: Ensembl
- protein destabilization Source: Ensembl
- protein homooligomerization Source: InterPro
- regulation of intracellular calcium activated chloride channel activity Source: Ensembl
Keywordsi
Molecular function | Prion |
Ligand | Copper, Metal-binding, Zinc |
Protein family/group databases
TCDBi | 1.C.48.1.1, the prion peptide (prp) family |
Names & Taxonomyi
Protein namesi | Recommended name: Major prion proteinShort name: PrP Alternative name(s): CD_antigen: CD230 |
Gene namesi | Name:PRNP Synonyms:PRP, SIP |
Organismi | Ovis aries (Sheep) |
Taxonomic identifieri | 9940 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Ovis |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; GPI-anchor By similarity
Golgi apparatus
- Golgi apparatus By similarity
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.By similarity
Cytosol
- cytosol Source: Ensembl
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Nucleus
- nuclear membrane Source: Ensembl
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- anchored component of membrane Source: UniProtKB-KW
- cell surface Source: Ensembl
- dendrite Source: Ensembl
- inclusion body Source: Ensembl
- membrane raft Source: Ensembl
Keywords - Cellular componenti
Amyloid, Cell membrane, Golgi apparatus, MembranePathology & Biotechi
Involvement in diseasei
Keywords - Diseasei
Disease variantChemistry databases
ChEMBLi | CHEMBL2406893 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Add BLAST | 24 | |
ChainiPRO_0000025727 | 25 – 233 | Major prion proteinAdd BLAST | 209 | |
PropeptideiPRO_0000025728 | 234 – 256 | Removed in mature formSequence analysisAdd BLAST | 23 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 182 ↔ 217 | |||
Glycosylationi | 184 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Glycosylationi | 200 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Lipidationi | 233 | GPI-anchor amidated alanineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, LipoproteinPTM databases
GlyConnecti | 2954, 70 N-Linked glycans (2 sites) 2955, 70 N-Linked glycans (2 sites) |
Interactioni
Subunit structurei
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.
By similarityBinary interactionsi
P23907
With | #Exp. | IntAct |
---|---|---|
itself | 3 | EBI-7670302,EBI-7670302 |
PRNP [P04156] from Homo sapiens. | 3 | EBI-7670302,EBI-977302 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- microtubule binding Source: AgBase
- tubulin binding Source: AgBase
- type 5 metabotropic glutamate receptor binding Source: Ensembl
Protein-protein interaction databases
DIPi | DIP-60917N |
IntActi | P23907, 1 interactor |
MINTi | P23907 |
STRINGi | 9940.ENSOARP00000004991 |
Chemistry databases
BindingDBi | P23907 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P23907 |
BMRBi | P23907 |
SASBDBi | P23907 |
SMRi | P23907 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P23907 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 54 – 62 | 1 | 9 | |
Repeati | 63 – 70 | 2 | 8 | |
Repeati | 71 – 78 | 3 | 8 | |
Repeati | 79 – 86 | 4 | 8 | |
Repeati | 87 – 95 | 5 | 9 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 25 – 233 | Interaction with GRB2, ERI3 and SYN1By similarityAdd BLAST | 209 | |
Regioni | 28 – 110 | DisorderedSequence analysisAdd BLAST | 83 | |
Regioni | 54 – 95 | 5 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd BLAST | 42 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | ENOG502S2A8, Eukaryota |
HOGENOMi | CLU_094631_0_0_1 |
OMAi | HNPGYPH |
Family and domain databases
Gene3Di | 1.10.790.10, 1 hit |
InterProi | View protein in InterPro IPR000817, Prion IPR036924, Prion/Doppel_b-ribbon_dom_sf IPR022416, Prion/Doppel_prot_b-ribbon_dom IPR025860, Prion_N_dom |
Pfami | View protein in Pfam PF00377, Prion, 1 hit PF11587, Prion_bPrPp, 1 hit |
PRINTSi | PR00341, PRION |
SMARTi | View protein in SMART SM00157, PRP, 1 hit |
SUPFAMi | SSF54098, SSF54098, 1 hit |
PROSITEi | View protein in PROSITE PS00291, PRION_1, 1 hit PS00706, PRION_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN
60 70 80 90 100
RYPPQGGGGW GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS
110 120 130 140 150
QWNKPSKPKT NMKHVAGAAA AGAVVGGLGG YMLGSAMSRP LIHFGNDYED
160 170 180 190 200
RYYRENMYRY PNQVYYRPVD RYSNQNNFVH DCVNITVKQH TVTTTTKGEN
210 220 230 240 250
FTETDIKIME RVVEQMCITQ YQRESQAYYQ RGASVILFSS PPVILLISFL
IFLIVG
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 112 | M → T1 Publication | 1 | |
Natural varianti | 136 | A → T1 Publication | 1 | |
Natural varianti | 136 | A → V in scrapie; short incubation; sA allele. 6 Publications | 1 | |
Natural varianti | 137 | M → T1 Publication | 1 | |
Natural varianti | 141 | L → F3 Publications | 1 | |
Natural varianti | 154 | R → H4 Publications | 1 | |
Natural varianti | 171 | R → H in scrapie; low incidence. 1 Publication | 1 | |
Natural varianti | 171 | R → K1 Publication | 1 | |
Natural varianti | 171 | R → Q Linked to susceptibility to scrapie. 9 Publications | 1 | |
Natural varianti | 211 | R → Q3 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M31313 Genomic DNA Translation: AAB97765.1 X79912 Genomic DNA Translation: CAA56283.1 U67922 Genomic DNA Translation: AAC78726.1 AJ223072 Genomic DNA Translation: CAA11073.1 AY350241 Genomic DNA Translation: AAR14214.1 AY350242 Genomic DNA Translation: AAR14215.1 AY350243 Genomic DNA Translation: AAR14216.1 AY350245 Genomic DNA Translation: AAR14218.1 AY350246 Genomic DNA Translation: AAR14219.1 AY350248 Genomic DNA Translation: AAR14221.1 AY350249 Genomic DNA Translation: AAR14222.1 AY350250 Genomic DNA Translation: AAR14223.1 AY350254 Genomic DNA Translation: AAR14227.1 AY350256 Genomic DNA Translation: AAR14229.1 AY350257 Genomic DNA Translation: AAR14230.1 AY350261 Genomic DNA Translation: AAR14234.1 AY350264 Genomic DNA Translation: AAR14237.1 AY350267 Genomic DNA Translation: AAR14240.1 AY350268 Genomic DNA Translation: AAR14241.1 AY350271 Genomic DNA Translation: AAR14244.1 AY350272 Genomic DNA Translation: AAR14245.1 AY350273 Genomic DNA Translation: AAR14246.1 AY350275 Genomic DNA Translation: AAR14248.1 AJ567984 Genomic DNA Translation: CAE00186.1 AJ567985 Genomic DNA Translation: CAE00187.1 AJ567986 Genomic DNA Translation: CAE00188.2 AJ567988 Genomic DNA Translation: CAE00190.1 D38179 Genomic DNA Translation: BAA07376.1 AJ000680 Genomic DNA Translation: CAA04235.1 AJ000681 Genomic DNA Translation: CAA04236.1 AJ000736 Genomic DNA Translation: CAA04274.1 AJ000738 Genomic DNA Translation: CAA04276.1 AJ000739 Genomic DNA Translation: CAA04277.1 AY907685 Genomic DNA Translation: AAW88332.1 AY907689 Genomic DNA Translation: AAW88336.1 AY907690 Genomic DNA Translation: AAW88337.1 AY907691 Genomic DNA Translation: AAW88338.1 |
RefSeqi | NP_001009481.1, NM_001009481.1 XP_012043480.1, XM_012188090.2 |
Genome annotation databases
Ensembli | ENSOART00000005076; ENSOARP00000004991; ENSOARG00000004668 |
GeneIDi | 493887 |
KEGGi | oas:493887 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M31313 Genomic DNA Translation: AAB97765.1 X79912 Genomic DNA Translation: CAA56283.1 U67922 Genomic DNA Translation: AAC78726.1 AJ223072 Genomic DNA Translation: CAA11073.1 AY350241 Genomic DNA Translation: AAR14214.1 AY350242 Genomic DNA Translation: AAR14215.1 AY350243 Genomic DNA Translation: AAR14216.1 AY350245 Genomic DNA Translation: AAR14218.1 AY350246 Genomic DNA Translation: AAR14219.1 AY350248 Genomic DNA Translation: AAR14221.1 AY350249 Genomic DNA Translation: AAR14222.1 AY350250 Genomic DNA Translation: AAR14223.1 AY350254 Genomic DNA Translation: AAR14227.1 AY350256 Genomic DNA Translation: AAR14229.1 AY350257 Genomic DNA Translation: AAR14230.1 AY350261 Genomic DNA Translation: AAR14234.1 AY350264 Genomic DNA Translation: AAR14237.1 AY350267 Genomic DNA Translation: AAR14240.1 AY350268 Genomic DNA Translation: AAR14241.1 AY350271 Genomic DNA Translation: AAR14244.1 AY350272 Genomic DNA Translation: AAR14245.1 AY350273 Genomic DNA Translation: AAR14246.1 AY350275 Genomic DNA Translation: AAR14248.1 AJ567984 Genomic DNA Translation: CAE00186.1 AJ567985 Genomic DNA Translation: CAE00187.1 AJ567986 Genomic DNA Translation: CAE00188.2 AJ567988 Genomic DNA Translation: CAE00190.1 D38179 Genomic DNA Translation: BAA07376.1 AJ000680 Genomic DNA Translation: CAA04235.1 AJ000681 Genomic DNA Translation: CAA04236.1 AJ000736 Genomic DNA Translation: CAA04274.1 AJ000738 Genomic DNA Translation: CAA04276.1 AJ000739 Genomic DNA Translation: CAA04277.1 AY907685 Genomic DNA Translation: AAW88332.1 AY907689 Genomic DNA Translation: AAW88336.1 AY907690 Genomic DNA Translation: AAW88337.1 AY907691 Genomic DNA Translation: AAW88338.1 |
RefSeqi | NP_001009481.1, NM_001009481.1 XP_012043480.1, XM_012188090.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1G04 | NMR | - | A | 145-169 | [»] | |
1M25 | NMR | - | A | 145-169 | [»] | |
1S4T | NMR | - | A | 138-158 | [»] | |
1TPX | X-ray | 2.56 | A | 114-234 | [»] | |
1TQB | X-ray | 2.55 | A | 127-228 | [»] | |
1TQC | X-ray | 2.80 | A | 127-228 | [»] | |
1UW3 | X-ray | 2.04 | A | 128-233 | [»] | |
1XYU | NMR | - | A | 124-234 | [»] | |
1Y2S | NMR | - | A | 124-234 | [»] | |
2KTM | NMR | - | A | 172-234 | [»] | |
2MV8 | NMR | - | A | 103-234 | [»] | |
2MV9 | NMR | - | A | 103-234 | [»] | |
2N53 | NMR | - | A | 103-234 | [»] | |
2RMV | NMR | - | A | 145-169 | [»] | |
2RMW | NMR | - | A | 145-169 | [»] | |
AlphaFoldDBi | P23907 | |||||
BMRBi | P23907 | |||||
SASBDBi | P23907 | |||||
SMRi | P23907 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-60917N |
IntActi | P23907, 1 interactor |
MINTi | P23907 |
STRINGi | 9940.ENSOARP00000004991 |
Chemistry databases
BindingDBi | P23907 |
ChEMBLi | CHEMBL2406893 |
Protein family/group databases
TCDBi | 1.C.48.1.1, the prion peptide (prp) family |
PTM databases
GlyConnecti | 2954, 70 N-Linked glycans (2 sites) 2955, 70 N-Linked glycans (2 sites) |
Protocols and materials databases
ABCDi | P23907, 1 sequenced antibody |
Genome annotation databases
Ensembli | ENSOART00000005076; ENSOARP00000004991; ENSOARG00000004668 |
GeneIDi | 493887 |
KEGGi | oas:493887 |
Organism-specific databases
CTDi | 5621 |
Phylogenomic databases
eggNOGi | ENOG502S2A8, Eukaryota |
HOGENOMi | CLU_094631_0_0_1 |
OMAi | HNPGYPH |
Miscellaneous databases
EvolutionaryTracei | P23907 |
PROi | PR:P23907 |
Gene expression databases
ExpressionAtlasi | P23907, baseline |
Family and domain databases
Gene3Di | 1.10.790.10, 1 hit |
InterProi | View protein in InterPro IPR000817, Prion IPR036924, Prion/Doppel_b-ribbon_dom_sf IPR022416, Prion/Doppel_prot_b-ribbon_dom IPR025860, Prion_N_dom |
Pfami | View protein in Pfam PF00377, Prion, 1 hit PF11587, Prion_bPrPp, 1 hit |
PRINTSi | PR00341, PRION |
SMARTi | View protein in SMART SM00157, PRP, 1 hit |
SUPFAMi | SSF54098, SSF54098, 1 hit |
PROSITEi | View protein in PROSITE PS00291, PRION_1, 1 hit PS00706, PRION_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PRIO_SHEEP | |
Accessioni | P23907Primary (citable) accession number: P23907 Secondary accession number(s): Q5ECG0 Q7JGT4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1991 |
Last sequence update: | November 1, 1991 | |
Last modified: | May 25, 2022 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families