Search Results
Overview
| Uniprot ID | Q99497 |
|---|---|
| Protein Name | Parkinson disease protein 7 |
| Gene Name | PARK7 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 12 | RALVILAKGAEEMET |
| 122 | HEIGFGSKVTTHPLA |
| 130 | VTTHPLAKDKMMNGG |
| 132 | THPLAKDKMMNGGHY |
| 148 | YSENRVEKDGLILTS |
| 182 | KEVAAQVKAPLVLKD |
| 188 | VKAPLVLKD****** |
| 32 | VMRRAGIKVTVAGLA |
| 41 | TVAGLAGKDPVQCSR |
| 62 | DASLEDAKKEGPYDV |
| 63 | ASLEDAKKEGPYDVV |
| 93 | AAVKEILKEQENRKG |
| 99 | LKEQENRKGLIAAIC |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Molecular Function | GO:0030414 | peptidase inhibitor activity |
| Cellular Component | GO:0005912 | adherens junction |
| Cellular Component | GO:0030424 | axon |
| Cellular Component | GO:0044297 | cell body |
| Cellular Component | GO:0000785 | chromatin |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0045121 | membrane raft |
| Cellular Component | GO:0005758 | mitochondrial intermembrane space |
| Cellular Component | GO:0005759 | mitochondrial matrix |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0016605 | PML body |
| Cellular Component | GO:0008021 | synaptic vesicle |
| Molecular Function | GO:0045296 | cadherin binding |
| Molecular Function | GO:0005507 | copper ion binding |
| Molecular Function | GO:1903135 | cupric ion binding |
| Molecular Function | GO:1903136 | cuprous ion binding |
| Molecular Function | GO:0019955 | cytokine binding |
| Molecular Function | GO:0140297 | DNA-binding transcription factor binding |
| Molecular Function | GO:0008047 | enzyme activator activity |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:1990422 | glyoxalase (glycolic acid-forming) activity |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0019900 | kinase binding |
| Molecular Function | GO:0036478 | L-dopa decarboxylase activator activity |
| Molecular Function | GO:0045340 | mercury ion binding |
| Molecular Function | GO:0003729 | mRNA binding |
| Molecular Function | GO:0050681 | nuclear androgen receptor binding |
| Molecular Function | GO:0016684 | oxidoreductase activity, acting on peroxide as acceptor |
| Molecular Function | GO:0019826 | oxygen sensor activity |
| Molecular Function | GO:0008233 | peptidase activity |
| Biological Process | GO:0007265 | Ras protein signal transduction |
| Biological Process | GO:0060765 | regulation of androgen receptor signaling pathway |
| Biological Process | GO:0050727 | regulation of inflammatory response |
| Biological Process | GO:0051881 | regulation of mitochondrial membrane potential |
| Biological Process | GO:0043523 | regulation of neuron apoptotic process |
| Biological Process | GO:1903376 | regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| Biological Process | GO:1902903 | regulation of supramolecular fiber organization |
| Biological Process | GO:1900242 | regulation of synaptic vesicle endocytosis |
| Biological Process | GO:0019430 | removal of superoxide radicals |
| Biological Process | GO:0006979 | response to oxidative stress |
| Biological Process | GO:0007338 | single fertilization |
| Molecular Function | GO:0051920 | peroxiredoxin activity |
| Molecular Function | GO:0036524 | protein deglycase activity |
| Molecular Function | GO:0042803 | protein homodimerization activity |
| Molecular Function | GO:0097110 | scaffold protein binding |
| Molecular Function | GO:0030546 | signaling receptor activator activity |
| Molecular Function | GO:0005102 | signaling receptor binding |
| Molecular Function | GO:0044388 | small protein activating enzyme binding |
| Molecular Function | GO:0016532 | superoxide dismutase copper chaperone activity |
| Molecular Function | GO:0003713 | transcription coactivator activity |
| Molecular Function | GO:0036470 | tyrosine 3-monooxygenase activator activity |
| Molecular Function | GO:0044390 | ubiquitin-like protein conjugating enzyme binding |
| Molecular Function | GO:0055105 | ubiquitin-protein transferase inhibitor activity |
| Molecular Function | GO:1990381 | ubiquitin-specific protease binding |
| Biological Process | GO:0030521 | androgen receptor signaling pathway |
| Biological Process | GO:0006914 | autophagy |
| Biological Process | GO:0110095 | cellular detoxification of aldehyde |
| Biological Process | GO:0140041 | cellular detoxification of methylglyoxal |
| Biological Process | GO:0036471 | cellular response to glyoxal |
| Biological Process | GO:0070301 | cellular response to hydrogen peroxide |
| Biological Process | GO:0034599 | cellular response to oxidative stress |
| Biological Process | GO:0070994 | detection of oxidative stress |
| Biological Process | GO:0010273 | detoxification of copper ion |
| Biological Process | GO:0061691 | detoxification of hydrogen peroxide |
| Biological Process | GO:0050787 | detoxification of mercury ion |
| Biological Process | GO:0006281 | DNA repair |
| Biological Process | GO:0042593 | glucose homeostasis |
| Biological Process | GO:0046295 | glycolate biosynthetic process |
| Biological Process | GO:1903189 | glyoxal metabolic process |
| Biological Process | GO:0106044 | guanine deglycation |
| Biological Process | GO:0106046 | guanine deglycation, glyoxal removal |
| Biological Process | GO:0106045 | guanine deglycation, methylglyoxal removal |
| Biological Process | GO:0042743 | hydrogen peroxide metabolic process |
| Biological Process | GO:0006954 | inflammatory response |
| Biological Process | GO:0030073 | insulin secretion |
| Biological Process | GO:0019249 | lactate biosynthetic process |
| Biological Process | GO:0061727 | methylglyoxal catabolic process to lactate |
| Biological Process | GO:0009438 | methylglyoxal metabolic process |
| Biological Process | GO:0007005 | mitochondrion organization |
| Biological Process | GO:1903073 | negative regulation of death-inducing signaling complex assembly |
| Biological Process | GO:1902236 | negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:2001237 | negative regulation of extrinsic apoptotic signaling pathway |
| Biological Process | GO:0010629 | negative regulation of gene expression |
| Biological Process | GO:1903384 | negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway |
| Biological Process | GO:1903751 | negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide |
| Biological Process | GO:0043524 | negative regulation of neuron apoptotic process |
| Biological Process | GO:1905259 | negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:1902176 | negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:1903377 | negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| Biological Process | GO:0032435 | negative regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process | GO:0046826 | negative regulation of protein export from nucleus |
| Biological Process | GO:1903094 | negative regulation of protein K48-linked deubiquitination |
| Biological Process | GO:0033234 | negative regulation of protein sumoylation |
| Biological Process | GO:0031397 | negative regulation of protein ubiquitination |
| Biological Process | GO:1903427 | negative regulation of reactive oxygen species biosynthetic process |
| Biological Process | GO:1903122 | negative regulation of TRAIL-activated apoptotic signaling pathway |
| Biological Process | GO:0002866 | positive regulation of acute inflammatory response to antigenic stimulus |
| Biological Process | GO:1903599 | positive regulation of autophagy of mitochondrion |
| Biological Process | GO:1903181 | positive regulation of dopamine biosynthetic process |
| Biological Process | GO:0010628 | positive regulation of gene expression |
| Biological Process | GO:0032757 | positive regulation of interleukin-8 production |
| Biological Process | GO:1903197 | positive regulation of L-dopa biosynthetic process |
| Biological Process | GO:1902958 | positive regulation of mitochondrial electron transport, NADH to ubiquinone |
| Biological Process | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process | GO:1900182 | positive regulation of protein localization to nucleus |
| Biological Process | GO:0031334 | positive regulation of protein-containing complex assembly |
| Biological Process | GO:2000379 | positive regulation of reactive oxygen species metabolic process |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0030091 | protein repair |
| Biological Process | GO:0050821 | protein stabilization |
| Biological Process | GO:0006508 | proteolysis |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[5] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.