InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PARK7

Summary

InnateDB Protein

IDBP-88300.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PARK7

Protein Name

parkinson protein 7

Synonyms

DJ-1; DJ1; HEL-S-67p;

Species

Homo sapiens

Ensembl Protein

ENSP00000340278

InnateDB Gene

IDBG-88298 (PARK7)

Protein Structure

UniProt Annotation

Function

Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone. May regulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. {ECO:0000269PubMed:11477070, ECO:0000269PubMed:12612053, ECO:0000269PubMed:12939276, ECO:0000269PubMed:14749723, ECO:0000269PubMed:15181200, ECO:0000269PubMed:15502874, ECO:0000269PubMed:15976810, ECO:0000269PubMed:16390825, ECO:0000269PubMed:17015834, ECO:0000269PubMed:18626009, ECO:0000269PubMed:18711745, ECO:0000269PubMed:20304780, ECO:0000269PubMed:21097510, ECO:0000269PubMed:23847046, ECO:0000269PubMed:9070310}.

Subcellular Localization

Cell membrane; Lipid-anchor. Cytoplasm. Nucleus. Membrane raft. Mitochondrion. Note=Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage. Detected in tau inclusions in brains from neurodegenerative disease patients. Membrane raft localization in astrocytes and neuronal cells requires palmitoylation.

Disease Associations

Parkinson disease 7 (PARK7) [MIM:606324]: A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis- parkinsonism/dementia complex (Guam disease). {ECO:0000269PubMed:12446870, ECO:0000269PubMed:12953260, ECO:0000269PubMed:15254937, ECO:0000269PubMed:15365989}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain. Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa. {ECO:0000269PubMed:14579415, ECO:0000269PubMed:14662519, ECO:0000269PubMed:14705119, ECO:0000269PubMed:9070310}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 90 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	90 [view]
Protein-Protein	89 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003729	mRNA binding
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008233	peptidase activity
GO:0016532	superoxide dismutase copper chaperone activity
GO:0016684	oxidoreductase activity, acting on peroxide as acceptor
GO:0019899	enzyme binding
GO:0019955	cytokine binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0044388	small protein activating enzyme binding
GO:0044390	small protein conjugating enzyme binding
GO:0050681	androgen receptor binding
GO:0097110	scaffold protein binding
GO:1903135	cupric ion binding
GO:1903136	cuprous ion binding
GO:1990381	ubiquitin-specific protease binding

Biological Process

GO:0001933	negative regulation of protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0006508	proteolysis
GO:0006914	autophagy
GO:0006954	inflammatory response
GO:0007005	mitochondrion organization
GO:0007338	single fertilization
GO:0010629	negative regulation of gene expression
GO:0032091	negative regulation of protein binding
GO:0032757	positive regulation of interleukin-8 production
GO:0034599	cellular response to oxidative stress
GO:0042743	hydrogen peroxide metabolic process
GO:0043523	regulation of neuron apoptotic process
GO:0043524	negative regulation of neuron apoptotic process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046826	negative regulation of protein export from nucleus
GO:0050727	regulation of inflammatory response
GO:0050821	protein stabilization
GO:0051881	regulation of mitochondrial membrane potential
GO:0055114	oxidation-reduction process
GO:0060548	negative regulation of cell death
GO:0060765	regulation of androgen receptor signaling pathway
GO:0070301	cellular response to hydrogen peroxide
GO:0090073	positive regulation of protein homodimerization activity
GO:1900182	positive regulation of protein localization to nucleus
GO:1901215	negative regulation of neuron death
GO:1901299	negative regulation of hydrogen peroxide-mediated programmed cell death
GO:1901671	positive regulation of superoxide dismutase activity
GO:1901984	negative regulation of protein acetylation
GO:1903073	negative regulation of death-inducing signaling complex assembly
GO:1903094	negative regulation of protein K48-linked deubiquitination
GO:1903122	negative regulation of TRAIL-activated apoptotic signaling pathway
GO:2000157	negative regulation of ubiquitin-specific protease activity
GO:2000825	positive regulation of androgen receptor activity
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway
GO:2001268	negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0016605	PML body
GO:0045121	membrane raft
GO:0070062	extracellular vesicular exosome