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PMID:23626584

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Citation

Trempe, JF and Fon, EA (2013) Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection. Front Neurol 4:38

Abstract

Autosomal recessive forms of Parkinson's disease are caused by mutations in three genes: Parkin, PINK1, and DJ-1. These genes encode for proteins with distinct enzymatic activities that may work together to confer neuroprotection. Parkin is an E3 ubiquitin ligase that has been shown to ubiquitinate substrates and to trigger proteasome-dependent degradation or autophagy, two crucial homeostatic processes in neurons. PINK1 is a mitochondrial protein kinase whose activity is required for Parkin-dependent mitophagy, a process that has been linked to neurodegeneration. Finally, DJ-1 is a protein homologous to a broad class of bacterial enzymes that may function as a sensor and modulator of reactive oxygen species, which have been implicated in neurodegenerative diseases. Here, we review the literature on the structure and biochemical functions of these three proteins.

Links

PubMed PMC3630392 Online version:10.3389/fneur.2013.00038

Keywords


Significance

Annotations

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

HUMAN:PRKN

involved_in

GO:0032368: regulation of lipid transport

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0010906: regulation of glucose metabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0017124: SH3 domain binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0008270: zinc ion binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0044314: protein K27-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0042417: dopamine metabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0085020: protein K6-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0035519: protein K29-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:1903351: cellular response to dopamine

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ABL1

involved_in

GO:0018108: peptidyl-tyrosine phosphorylation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ABL1

involved_in

GO:0051444: negative regulation of ubiquitin-protein transferase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • has_input:(UniProtKB:O60260)

Seeded From UniProt

complete

HUMAN:PARK7

involved_in

GO:1902903: regulation of supramolecular fiber organization

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • has_input:(UniProtKB:P37840)

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0044314: protein K27-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion


P

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0017124: SH3 domain binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0032368: regulation of lipid transport

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:1903351: cellular response to dopamine

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0008270: zinc ion binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0035519: protein K29-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0085020: protein K6-linked ubiquitination

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0042417: dopamine metabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0010906: regulation of glucose metabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PINK1

involved_in

GO:0036289: peptidyl-serine autophosphorylation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PINK1

involved_in

GO:0018105: peptidyl-serine phosphorylation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PARK7

involved_in

GO:1902903: regulation of supramolecular fiber organization

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

has_regulation_target:(UniProtKB:P37840)

Seeded From UniProt

complete

Notes

See also

References

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