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: 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:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, 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:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:9070310}.
 
Biophysicochemical properties: Kinetic parameters: KM=173.4 uM for casein {ECO:0000269|PubMed:20304780};
Subunit: Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N- terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF. {ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:21097510}.
Subcellular location: 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.
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: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}.
Ptm: Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
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.