PRIO_RABIT
ID PRIO_RABIT Reviewed; 252 AA.
AC Q95211;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: Full=PrP27-30;
DE AltName: Full=PrP33-35C;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=New Zealand white;
RX PubMed=9031631; DOI=10.1016/s0378-1119(96)00598-7;
RA Loftus B., Rogers M.;
RT "Characterization of a prion protein (PrP) gene from rabbit; a species with
RT apparent resistance to infection by prions.";
RL Gene 184:215-219(1997).
RN [2]
RP STRUCTURE BY NMR OF 91-228 OF WILD TYPE AND MUTANT ASN-173, AND DISULFIDE
RP BOND.
RX PubMed=20639199; DOI=10.1074/jbc.m110.118844;
RA Wen Y., Li J., Yao W., Xiong M., Hong J., Peng Y., Xiao G., Lin D.;
RT "Unique structural characteristics of the rabbit prion protein.";
RL J. Biol. Chem. 285:31682-31693(2010).
CC -!- FUNCTION: Its primary physiological function is unclear. Has
CC cytoprotective activity against internal or environmental stresses. May
CC play a role in neuronal development and synaptic plasticity. May be
CC required for neuronal myelin sheath maintenance. May play a role in
CC iron uptake and iron homeostasis. Soluble oligomers are toxic to
CC cultured neuroblastoma cells and induce apoptosis (in vitro).
CC Association with GPC1 (via its heparan sulfate chains) targets PRNP to
CC lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated
CC GPC1 deaminase degradation of its heparan sulfate side chains (By
CC similarity). {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Soluble oligomers may represent an
CC intermediate stage on the path to fibril formation. Copper binding may
CC promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and
CC SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this
CC interaction alters MGRN1 subcellular location and causes lysosomal
CC enlargement. Interacts with KIAA1191. {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- INTERACTION:
CC Q95211; Q95211: PRNP; NbExp=2; IntAct=EBI-15889930, EBI-15889930;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04156};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P04156}. Golgi
CC apparatus {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts
CC via association with the heparan sulfate chains of GPC1. Colocates, in
CC the presence of Cu(2+), to vesicles in para- and perinuclear regions,
CC where both proteins undergo internalization. Heparin displaces PRNP
CC from lipid rafts and promotes endocytosis.
CC {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: The normal, monomeric form has a mainly alpha-helical
CC structure. The disease-associated, protease-resistant form forms
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Disease mutations may favor
CC intermolecular contacts via short beta strands, and may thereby trigger
CC oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. At
CC low copper concentrations, the sidechains of His residues from three or
CC four repeats contribute to the binding of a single copper ion.
CC Alternatively, a copper ion can be bound by interaction with the
CC sidechain and backbone amide nitrogen of a single His residue. The
CC observed copper binding stoichiometry suggests that two repeat regions
CC cooperate to stabilize the binding of a single copper ion. At higher
CC copper concentrations, each octamer can bind one copper ion by
CC interactions with the His sidechain and Gly backbone atoms. A mixture
CC of binding types may occur, especially in the case of octamer repeat
CC expansion. Copper binding may stabilize the conformation of this region
CC and may promote oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DISEASE: Note=Found in high quantity in the brain of humans and animals
CC infected with degenerative neurological diseases such as kuru,
CC Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS),
CC scrapie, bovine spongiform encephalopathy (BSE), transmissible mink
CC encephalopathy (TME), etc. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; U28334; AAC48697.1; -; Genomic_DNA.
DR PIR; JC6175; JC6175.
DR RefSeq; XP_008254357.1; XM_008256135.2.
DR RefSeq; XP_008254358.1; XM_008256136.2.
DR PDB; 2FJ3; NMR; -; A=91-228.
DR PDB; 2JOH; NMR; -; A=91-228.
DR PDB; 2JOM; NMR; -; A=91-228.
DR PDB; 4HLS; X-ray; 1.45 A; A/B=119-229.
DR PDB; 4HMM; X-ray; 1.50 A; A/B=119-229.
DR PDB; 4HMR; X-ray; 1.60 A; A/B=119-229.
DR PDBsum; 2FJ3; -.
DR PDBsum; 2JOH; -.
DR PDBsum; 2JOM; -.
DR PDBsum; 4HLS; -.
DR PDBsum; 4HMM; -.
DR PDBsum; 4HMR; -.
DR AlphaFoldDB; Q95211; -.
DR BMRB; Q95211; -.
DR SMR; Q95211; -.
DR DIP; DIP-59794N; -.
DR STRING; 9986.ENSOCUP00000001797; -.
DR PRIDE; Q95211; -.
DR Ensembl; ENSOCUT00000002082; ENSOCUP00000001797; ENSOCUG00000002086.
DR GeneID; 100008658; -.
DR CTD; 5621; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR GeneTree; ENSGT00510000049083; -.
DR HOGENOM; CLU_094631_0_0_1; -.
DR InParanoid; Q95211; -.
DR OMA; HNPGYPH; -.
DR TreeFam; TF105188; -.
DR EvolutionaryTrace; Q95211; -.
DR Proteomes; UP000001811; Chromosome 4.
DR Bgee; ENSOCUG00000002086; Expressed in prefrontal cortex and 6 other tissues.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016234; C:inclusion body; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:1903135; F:cupric ion binding; IEA:Ensembl.
DR GO; GO:1903136; F:cuprous ion binding; IEA:Ensembl.
DR GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IEA:Ensembl.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0032147; P:activation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1990535; P:neuron projection maintenance; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IEA:Ensembl.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR000817; Prion.
DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR InterPro; IPR020949; Prion_copper_b_octapeptide.
DR InterPro; IPR025860; Prion_N_dom.
DR Pfam; PF00377; Prion; 1.
DR Pfam; PF11587; Prion_bPrPp; 1.
DR Pfam; PF03991; Prion_octapep; 5.
DR PRINTS; PR00341; PRION.
DR SMART; SM00157; PRP; 1.
DR SUPFAM; SSF54098; SSF54098; 1.
DR PROSITE; PS00291; PRION_1; 1.
DR PROSITE; PS00706; PRION_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Cell membrane; Copper; Disulfide bond; Glycoprotein;
KW Golgi apparatus; GPI-anchor; Lipoprotein; Membrane; Metal-binding; Prion;
KW Reference proteome; Repeat; Signal; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..229
FT /note="Major prion protein"
FT /id="PRO_0000025721"
FT PROPEP 230..252
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025722"
FT REPEAT 51..59
FT /note="1"
FT REPEAT 60..67
FT /note="2"
FT REPEAT 68..75
FT /note="3"
FT REPEAT 76..83
FT /note="4"
FT REPEAT 84..92
FT /note="5"
FT REGION 23..229
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 26..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..92
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 61
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 62
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 63
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 69
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 70
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 71
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 77
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 78
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 79
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 85
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 86
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 87
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 229
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 178..213
FT /evidence="ECO:0000269|PubMed:20639199"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:2FJ3"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:2JOH"
FT HELIX 143..152
FT /evidence="ECO:0007829|PDB:4HLS"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:4HLS"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4HMM"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:4HLS"
FT HELIX 171..191
FT /evidence="ECO:0007829|PDB:4HLS"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:4HLS"
FT HELIX 199..220
FT /evidence="ECO:0007829|PDB:4HLS"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:4HLS"
SQ SEQUENCE 252 AA; 27432 MW; 2E177AAF38B23A54 CRC64;
MAHLGYWMLL LFVATWSDVG LCKKRPKPGG GWNTGGSRYP GQSSPGGNRY PPQGGGWGQP
HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGTHNQWGK PSKPKTSMKH VAGAAAAGAV
VGGLGGYMLG SAMSRPLIHF GNDYEDRYYR ENMYRYPNQV YYRPVDQYSN QNSFVHDCVN
ITVKQHTVTT TTKGENFTET DIKIMERVVE QMCITQYQQE SQAAYQRAAG VLLFSSPPVI
LLISFLIFLI VG
