UniProt functional annotation for Q99497

UniProt code: Q99497.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteines, arginines and lysines 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) (PubMed:25416785). Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease; functions probably related to its primary function (PubMed:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, PubMed:25416785). 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:15502874, PubMed:14749723, PubMed:17015834, PubMed:21097510, PubMed:18711745). Its involvement in protein repair could also explain other unrelated functions. 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:19229105, PubMed:16632486). 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). 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). {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:9070310}.
 
Cofactor: Note=Does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate. {ECO:0000269|PubMed:25416785};
Biophysicochemical properties: Kinetic parameters: KM=173.4 uM for casein {ECO:0000269|PubMed:20304780}; KM=0.44 mM for glycated N-acetylarginine (at pH 7.0 and 22 degrees Celsius) {ECO:0000269|PubMed:25416785}; KM=0.35 mM for glycated N-acetyllysine (at pH 7.0 and 22 degrees Celsius) {ECO:0000269|PubMed:25416785}; KM=0.32 mM for glycated N-acetylcysteine (at pH 7.0 and 22 degrees Celsius) {ECO:0000269|PubMed:25416785}; Note=kcat is 0.27 sec(-1) for the deglycation of glycated N- acetylarginine. kcat is 0.28 sec(-1) for the deglycation of glycated N-acetyllysine. kcat is 0.42 sec(-1) for the deglycation of glycated N-acetylcysteine. {ECO:0000269|PubMed:25416785};
Subunit: Homodimer (PubMed:12851414, PubMed:12796482, PubMed:12855764). Binds EFCAB6/DJBP and PIAS2 (PubMed:11477070, PubMed:12851414, PubMed:12612053). Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR (PubMed:12612053). Interacts (via N-terminus) with OTUD7B (PubMed:21097510). Interacts with BBS1, HIPK1, CLCF1 and MTERF (PubMed:16390825, PubMed:21097510). Forms a complex with PINK1 and PARK2 (PubMed:19229105). {ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12796482, ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:21097510}.
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:O88767}; Lipid-anchor {ECO:0000250|UniProtKB:O88767}. Cytoplasm {ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:14579415, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:19229105}. Nucleus {ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:14579415, ECO:0000269|PubMed:15976810}. Membrane raft {ECO:0000250|UniProtKB:O88767}. Mitochondrion {ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105}. 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}.
Tissue specificity: Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain (at protein level). Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa. {ECO:0000269|PubMed:14579415, ECO:0000269|PubMed:14662519, ECO:0000269|PubMed:14705119, ECO:0000269|PubMed:9070310}.
Induction: By hydrogen peroxide and UV irradiation. {ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15976810}.
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}.
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:12953260, ECO:0000269|PubMed:15254937, ECO:0000269|PubMed:15365989}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarity: Belongs to the peptidase C56 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.