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PMID:11439185

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Citation

Imai, Y, Soda, M, Inoue, H, Hattori, N, Mizuno, Y and Takahashi, R (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105:891-902

Abstract

A putative G protein-coupled transmembrane polypeptide, named Pael receptor, was identified as an interacting protein with Parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When overexpressed in cells, this receptor tends to become unfolded, insoluble, and ubiquitinated in vivo. The insoluble Pael receptor leads to unfolded protein-induced cell death. Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. Moreover, the insoluble form of Pael receptor accumulates in the brains of AR-JP patients. Here, we show that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP.

Links

PubMed

Keywords

Acetylcysteine/analogs & derivatives; Acetylcysteine/pharmacology; Brain/cytology; Brain/metabolism; Cell Death; Cells, Cultured; Cysteine Proteinase Inhibitors/pharmacology; Endoplasmic Reticulum/metabolism; Humans; Ligases/genetics; Ligases/metabolism; Microscopy, Fluorescence; Parkinsonian Disorders/genetics; Parkinsonian Disorders/metabolism; Precipitin Tests; Protein Binding; Protein Folding; Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism; Recombinant Fusion Proteins/metabolism; Two-Hybrid System Techniques; Ubiquitin-Conjugating Enzymes; Ubiquitin-Protein Ligases; Ubiquitins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GPR37

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60260

F

  • occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

HUMAN:GPR37

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O15354

F

  • occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0016567: protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62253

F

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y385

F

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:1902236: negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2G1

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60260

F

Seeded From UniProt

complete

HUMAN:UB2J1

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60260

F

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

has_direct_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0016567: protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_direct_input:(UniProtKB:O15354)
  • part_of:(GO:0043161)

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

has_direct_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:1902236: negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y385

F

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62253

F

Seeded From UniProt

complete

HUMAN:GPR37

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:GPR37

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60260

F

occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

Notes

See also

References

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