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PRIO_SIGHI
ID   PRIO_SIGHI              Reviewed;         254 AA.
AC   Q9Z0T3;
DT   05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 96.
DE   RecName: Full=Major prion protein;
DE            Short=PrP;
DE   AltName: CD_antigen=CD230;
DE   Flags: Precursor;
GN   Name=PRNP; Synonyms=PRP;
OS   Sigmodon hispidus (Hispid cotton rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Sigmodontinae; Sigmodon.
OX   NCBI_TaxID=42415;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Brain;
RX   PubMed=10373359; DOI=10.1006/jmbi.1999.2831;
RA   Wopfner F., Weidenhofer G., Schneider R., von Brunn A., Gilch S.,
RA   Schwarz T.F., Werner T., Schatzl H.M.;
RT   "Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of
RT   flexible regions of the prion protein.";
RL   J. Mol. Biol. 289:1163-1178(1999).
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   -!- 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; AF117325; AAD19996.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9Z0T3; -.
DR   BMRB; Q9Z0T3; -.
DR   SMR; Q9Z0T3; -.
DR   GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR   GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
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; IPR025860; Prion_N_dom.
DR   Pfam; PF00377; Prion; 1.
DR   Pfam; PF11587; Prion_bPrPp; 1.
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   3: Inferred from homology;
KW   Amyloid; Cell membrane; Copper; Disulfide bond; Glycoprotein;
KW   Golgi apparatus; GPI-anchor; Lipoprotein; Membrane; Metal-binding; Prion;
KW   Repeat; Signal; Zinc.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000250"
FT   CHAIN           23..231
FT                   /note="Major prion protein"
FT                   /id="PRO_0000025729"
FT   PROPEP          232..254
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000025730"
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..91
FT                   /note="5"
FT   REGION          23..231
FT                   /note="Interaction with GRB2, ERI3 and SYN1"
FT                   /evidence="ECO:0000250|UniProtKB:P04925"
FT   REGION          25..107
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          51..91
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           231
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P04273"
FT   CARBOHYD        181
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        179..214
FT                   /evidence="ECO:0000250|UniProtKB:P04273"
SQ   SEQUENCE   254 AA;  27874 MW;  50C464D516E572DF CRC64;
     MANLGYWLLA LFVATWTDVG LCKKRPKPGG WNTGGSRYPG QGNPGGNRYP PQGGGTWGQP
     HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HVAGAAAAGA
     VVGGLGGYML GSAMSRPMIH FGNDWEDRYY RENMYRYPNQ VYYRPVDQYN NQNNFVHDCV
     NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCVTQYQK ESQAYYDGRR SSAVLFSSPP
     MILLISFLIF LIVG
 
 
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