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Protein

Major prion protein

Gene

Prnp

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 a 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi61Copper or zinc 1By similarity1
Metal bindingi62Copper or zinc 1; via amide nitrogenBy similarity1
Metal bindingi63Copper or zinc 1; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi69Copper or zinc 2By similarity1
Metal bindingi70Copper or zinc 2; via amide nitrogenBy similarity1
Metal bindingi71Copper or zinc 2; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi77Copper or zinc 3By similarity1
Metal bindingi78Copper or zinc 3; via amide nitrogenBy similarity1
Metal bindingi79Copper or zinc 3; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi85Copper or zinc 4By similarity1
Metal bindingi86Copper or zinc 4; via amide nitrogenBy similarity1
Metal bindingi87Copper or zinc 4; via amide nitrogen and carbonyl oxygenBy similarity1

GO - Molecular functioni

  • ATP-dependent protein binding Source: RGD
  • chaperone binding Source: RGD
  • copper ion binding Source: UniProtKB
  • ion channel binding Source: RGD
  • lamin binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Prion

Keywords - Ligandi

Copper, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Major prion protein
Short name:
PrP
Alternative name(s):
CD_antigen: CD230
Gene namesi
Name:Prnp
Synonyms:Prn, Prp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi3410. Prnp.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity
  • 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

GO - Cellular componenti

  • anchored component of plasma membrane Source: RGD
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • endoplasmic reticulum Source: Ensembl
  • extracellular exosome Source: Ensembl
  • Golgi apparatus Source: UniProtKB-SubCell
  • membrane Source: RGD
  • membrane raft Source: Ensembl
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000002572329 – 231Major prion proteinAdd BLAST203
PropeptideiPRO_0000025724232 – 254Removed in mature formBy similarityAdd BLAST23

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi179 ↔ 214By similarity
Glycosylationi181N-linked (GlcNAc...)Curated1
Glycosylationi197N-linked (GlcNAc...)Curated1
Lipidationi231GPI-anchor amidated serineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP13852.
PRIDEiP13852.

PTM databases

iPTMnetiP13852.
PhosphoSitePlusiP13852.

Expressioni

Gene expression databases

BgeeiENSRNOG00000021259.
GenevisibleiP13852. RN.

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 (By similarity). Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity). Interacts with APP. Interacts with KIAA1191 (By similarity). Interacts with ADGRG6 (By similarity).By similarity

GO - Molecular functioni

  • ATP-dependent protein binding Source: RGD
  • chaperone binding Source: RGD
  • ion channel binding Source: RGD
  • lamin binding Source: RGD

Protein-protein interaction databases

BioGridi246818. 2 interactors.
STRINGi10116.ENSRNOP00000028881.

Structurei

3D structure databases

ProteinModelPortaliP13852.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati51 – 5919
Repeati60 – 6728
Repeati68 – 7538
Repeati76 – 8348
Repeati84 – 9158

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni23 – 231Interaction with GRB2, ERI3 and SYN1By similarityAdd BLAST209
Regioni23 – 38Interaction with ADGRG6By similarityAdd BLAST16
Regioni51 – 915 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd BLAST41

Domaini

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.By similarity
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.By similarity

Sequence similaritiesi

Belongs to the prion family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOGENOMiHOG000232077.
HOVERGENiHBG008260.
InParanoidiP13852.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP13852.
TreeFamiTF105188.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
[Graphical view]
PRINTSiPR00341. PRION.
SMARTiSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMiSSF54098. SSF54098. 1 hit.
PROSITEiPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P13852-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANLGYWLLA LFVTTCTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP
60 70 80 90 100
PQSGGTWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWS QGGGTHNQWN
110 120 130 140 150
KPSKPKTNLK HVAGAAAAGA VVGGLGGYML GSAMSRPMLH FGNDWEDRYY
160 170 180 190 200
RENMYRYPNQ VYYRPVDQYS NQNNFVHDCV NITIKQHTVT TTTKGENFTE
210 220 230 240 250
TDVKMMERVV EQMCVTQYQK ESQAYYDGRR SSAVLFSSPP VILLISFLIF

LIVG
Length:254
Mass (Da):27,804
Last modified:November 1, 1997 - v2
Checksum:i28F424D13BEFA2C6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69654 Genomic DNA. Translation: AAB30728.2.
D50093 Genomic DNA. Translation: BAA08790.1.
AF117322 Genomic DNA. Translation: AAD19993.1.
BC072692 mRNA. Translation: AAH72692.1.
M20313 mRNA. Translation: AAA41947.1.
PIRiA53892.
RefSeqiNP_036763.1. NM_012631.2.
XP_006235124.1. XM_006235062.3.
UniGeneiRn.3936.

Genome annotation databases

EnsembliENSRNOT00000028881; ENSRNOP00000028881; ENSRNOG00000021259.
GeneIDi24686.
KEGGirno:24686.
UCSCiRGD:3410. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69654 Genomic DNA. Translation: AAB30728.2.
D50093 Genomic DNA. Translation: BAA08790.1.
AF117322 Genomic DNA. Translation: AAD19993.1.
BC072692 mRNA. Translation: AAH72692.1.
M20313 mRNA. Translation: AAA41947.1.
PIRiA53892.
RefSeqiNP_036763.1. NM_012631.2.
XP_006235124.1. XM_006235062.3.
UniGeneiRn.3936.

3D structure databases

ProteinModelPortaliP13852.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246818. 2 interactors.
STRINGi10116.ENSRNOP00000028881.

PTM databases

iPTMnetiP13852.
PhosphoSitePlusiP13852.

Proteomic databases

PaxDbiP13852.
PRIDEiP13852.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028881; ENSRNOP00000028881; ENSRNOG00000021259.
GeneIDi24686.
KEGGirno:24686.
UCSCiRGD:3410. rat.

Organism-specific databases

CTDi5621.
RGDi3410. Prnp.

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOGENOMiHOG000232077.
HOVERGENiHBG008260.
InParanoidiP13852.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP13852.
TreeFamiTF105188.

Miscellaneous databases

PROiP13852.

Gene expression databases

BgeeiENSRNOG00000021259.
GenevisibleiP13852. RN.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
[Graphical view]
PRINTSiPR00341. PRION.
SMARTiSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMiSSF54098. SSF54098. 1 hit.
PROSITEiPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPRIO_RAT
AccessioniPrimary (citable) accession number: P13852
Secondary accession number(s): Q549H6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.