PARK7
entrez
11315
canonical
uniprot
Q99497
canonical
ensembl
ENSG00000116288
resolver
ensp
ENSP00000340278
resolver
ensp
ENSP00000366708
resolver
ensp
ENSP00000366711
resolver
ensp
ENSP00000418770
resolver
ensp
ENSP00000465404
resolver
ensp
ENSP00000542682
resolver
ensp
ENSP00000542684
resolver
ensp
ENSP00000542687
resolver
ensp
ENSP00000542690
resolver
ensp
ENSP00000593356
resolver
ensp
ENSP00000593357
resolver
ensp
ENSP00000593358
resolver
enst
ENST00000338639
resolver
enst
ENST00000377488
resolver
enst
ENST00000377491
resolver
enst
ENST00000493373
resolver
enst
ENST00000493678
resolver
enst
ENST00000872623
resolver
enst
ENST00000872625
resolver
enst
ENST00000872628
resolver
enst
ENST00000872631
resolver
enst
ENST00000923297
resolver
enst
ENST00000923298
resolver
enst
ENST00000923299
resolver
genesymbol
HEL-S-67p
resolver
genesymbol
PARK7
resolver
hgnc
HGNC:16369
resolver
uniprot
B2R4Z1
resolver
uniprot
O14805
resolver
uniprot
Q6DR95
resolver
uniprot
Q7LFU2
resolver
uniprot
V9HWC2
resolver
uniprot_entry
PARK7_HUMAN
resolver
uniprot_entry
V9HWC2_HUMAN
resolver
uniprot_sec
B2R4Z1
resolver
uniprot_sec
O14805
resolver
uniprot_sec
Q6DR95
resolver
uniprot_sec
Q7LFU2
resolver
amino_acid_sequence
MASKRALVILAKGAEEMETVIPVDVMRRAGIKVTVAGLAGKDPVQCSRDVVICPDASLEDAKKEGPYDVVVLPGGNLGAQNLSESAAVKEILKEQENRKGLIAAICAGPTALLAHEIGFGSKVTTHPLAKDKMMNGGHYTYSENRVEKDGLILTSRGPGTSFEFALAIVEALNGKEVAAQVKAPLVLKD
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:12446870, ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:12953260, ECO:0000269|PubMed:14607841, ECO:0000269|PubMed:14713311, ECO:0000269|PubMed:15254937, ECO:0000269|PubMed:15365989, ECO:0000269|PubMed:16240358, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:18785233, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:26972524, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30928208}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.2.-
uniprot
proteins
ec_number
3.5.1.-
uniprot
proteins
ec_number
3.5.1.124
uniprot
proteins
function
FUNCTION: Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:12796482, PubMed:17015834, PubMed:18711745, PubMed:19229105, PubMed:20304780, PubMed:25416785, PubMed:26995087, PubMed:28993701). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:14749723, PubMed:15502874, PubMed:17015834, PubMed:18711745, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:25416785, PubMed:28596309). But this function is rebuted by other works (PubMed:27903648, PubMed:31653696). As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:25416785, PubMed:26995087, PubMed:28013050). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin (PubMed:30150385). Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels (PubMed:30150385, PubMed:30894531). Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093, PubMed:28993701, PubMed:31653696). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:16632486, PubMed:19229105). 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 (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30150385, ECO:0000269|PubMed:30894531, ECO:0000269|PubMed:9070310}.
uniprot
proteins
mass_dalton
19891
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="L->P: Abolishes detoxification activity on methylglyocal-adducted CoA."; /evidence="ECO:0000269|PubMed:28993701"; MUTAGEN 18; /note="E->A: Strongly decreases enzymatic activity. Almost abolishes detoxification activity on methylglyocal-adducted CoA."; /evidence="ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:28993701"; MUTAGEN 18; /note="E->D: Strongly decreases enzymatic activity."; /evidence="ECO:0000269|PubMed:22523093"; MUTAGEN 18; /note="E->N: Strongly decreases enzymatic activity."; /evidence="ECO:0000269|PubMed:22523093"; MUTAGEN 18; /note="E->Q: Strongly decreases enzymatic activity."; /evidence="ECO:0000269|PubMed:22523093"; MUTAGEN 46; /note="C->A: Reduces protein stability. No effect on oxidation."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:23847046"; MUTAGEN 46; /note="C->A: Reduces protein stability. No effect on oxidation. Reduced localization in lipid rafts; when associated with A-106."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:23847046"; MUTAGEN 46; /note="C->S: No effect on mitochondrial translocation neither on deglycase activity."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785"; MUTAGEN 51; /note="V->A: Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide."; /evidence="ECO:0000269|PubMed:14749723"; MUTAGEN 53; /note="C->A: Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide."; /evidence="ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:18711745"; MUTAGEN 53; /note="C->S: No effect on mitochondrial translocation neither on deglycase activity."; /evidence="ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:25416785"; MUTAGEN 106; /note="C->A: Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23847046"; MUTAGEN 106; /note="C->A: Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B. Removes the glycations and restores histone 3. Reduced localization in lipid rafts; when associated with A-46."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:30894531"; MUTAGEN 106; /note="C->D: Abolishes oxidation and association with mitochondria. No effect on chaperone activity."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:23847046"; MUTAGEN 106; /note="C->S: Loss of protein and nucleic acid deglycase activity. No effect on mitochondrial translocation. Reduced protease activity. No effect on protection against metal cytotoxicity. No effect on methylglyoxal-adducted glutathione or CoA."; /evidence="ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701"; MUTAGEN 126; /note="H->A: Strongly decreases enzymatic activity."; /evidence="ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:22523093"; MUTAGEN 130; /note="K->R: Partially compensates for loss of stability; when associated with P-166."; /evidence="ECO:0000269|PubMed:12851414"; MUTAGEN 179; /note="A->T: No effect on detoxification activity on methylglyocal-adducted CoA."; /evidence="ECO:0000269|PubMed:28993701
uniprot
proteins
post_translational_modification
PTM: Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity. {ECO:0000269|PubMed:15976810}.; PTM: Cys-106 is easily oxidized to sulfinic acid. {ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:15976810}.; PTM: Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress. {ECO:0000269|PubMed:20304780}.
uniprot
proteins
protein_family
Peptidase C56 family
uniprot
proteins
pubmed
11223268
uniprot
proteins
pubmed
11477070
uniprot
proteins
pubmed
12446870
uniprot
proteins
pubmed
12612053
uniprot
proteins
pubmed
12761214
uniprot
proteins
pubmed
12796482
uniprot
proteins
pubmed
12851414
uniprot
proteins
pubmed
12855764
uniprot
proteins
pubmed
12914946
uniprot
proteins
pubmed
12939276
uniprot
proteins
pubmed
12953260
uniprot
proteins
pubmed
14579415
uniprot
proteins
pubmed
14607841
uniprot
proteins
pubmed
14662519
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14705119
uniprot
proteins
pubmed
14705128
uniprot
proteins
pubmed
14713311
uniprot
proteins
pubmed
14749723
uniprot
proteins
pubmed
14872018
uniprot
proteins
pubmed
15181200
uniprot
proteins
pubmed
15254937
uniprot
proteins
pubmed
15365989
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15502874
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15976810
uniprot
proteins
pubmed
16240358
uniprot
proteins
pubmed
16390825
uniprot
proteins
pubmed
16632486
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17015834
uniprot
proteins
pubmed
17846173
uniprot
proteins
pubmed
18626009
uniprot
proteins
pubmed
18711745
uniprot
proteins
pubmed
18785233
uniprot
proteins
pubmed
19229105
uniprot
proteins
pubmed
20186336
uniprot
proteins
pubmed
20304780
uniprot
proteins
pubmed
21097510
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22523093
uniprot
proteins
pubmed
22611253
uniprot
proteins
pubmed
23792957
uniprot
proteins
pubmed
23847046
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25416785
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26972524
uniprot
proteins
pubmed
26995087
uniprot
proteins
pubmed
27903648
uniprot
proteins
pubmed
28013050
uniprot
proteins
pubmed
28596309
uniprot
proteins
pubmed
28993701
uniprot
proteins
pubmed
30150385
uniprot
proteins
pubmed
30894531
uniprot
proteins
pubmed
30928208
uniprot
proteins
pubmed
31536960
uniprot
proteins
pubmed
31653696
uniprot
proteins
pubmed
9070310
uniprot
proteins
sequence_length
189
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q99LX0}; Lipid-anchor {ECO:0000250|UniProtKB:Q99LX0}. Cytoplasm {ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:14579415, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:28596309}. Nucleus {ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:14579415, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:28596309}. Membrane raft {ECO:0000250|UniProtKB:O88767}. Mitochondrion {ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:31536960}. Endoplasmic reticulum {ECO:0000269|PubMed:31536960}. 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 (PubMed:18711745). Detected in tau inclusions in brains from neurodegenerative disease patients (PubMed:14705119). Membrane raft localization in astrocytes and neuronal cells requires palmitoylation. {ECO:0000269|PubMed:14705119, ECO:0000269|PubMed:18711745}.
uniprot
proteins