Parkinson disease protein 7 (PARK7)
The protein contains 189 amino acids for an estimated molecular weight of 19891 Da.
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:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, 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:15502874, PubMed:14749723, PubMed:17015834, PubMed:21097510, PubMed:18711745). 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) t (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Activation of protein kinase B activity
Adult locomotory behavior
Aggrephagy
Autophagy
Cellular detoxification of aldehyde
Cellular detoxification of methylglyoxal
Cellular response to glyoxal
Cellular response to hydrogen peroxide
Cellular response to oxidative stress
Detection of oxidative stress
Detoxification of copper ion
Detoxification of mercury ion
DNA repair
Dopamine uptake involved in synaptic transmission
Glucose homeostasis
Glutathione deglycation
Glycolate biosynthetic process
Glyoxal catabolic process
Glyoxal metabolic process
Guanine deglycation
Guanine deglycation, glyoxal removal
Guanine deglycation, methylglyoxal removal
Histone modification
Hydrogen peroxide metabolic process
Inflammatory response
Insulin secretion
Lactate biosynthetic process
Membrane depolarization
Membrane hyperpolarization
Methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione
Methylglyoxal catabolic process to lactate
Methylglyoxal metabolic process
Mitochondrion organization
Negative regulation of apoptotic process
Negative regulation of cell death
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Negative regulation of death-inducing signaling complex assembly
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Negative regulation of extrinsic apoptotic signaling pathway
Negative regulation of gene expression
Negative regulation of hydrogen peroxide-induced cell death
Negative regulation of hydrogen peroxide-induced neuron death
Negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
Negative regulation of neuron apoptotic process
Negative regulation of neuron death
Negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway
Negative regulation of oxidative stress-induced cell death
Negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Negative regulation of protein acetylation
Negative regulation of protein binding
Negative regulation of protein export from nucleus
Negative regulation of protein K48-linked deubiquitination
Negative regulation of protein kinase activity
Negative regulation of protein phosphorylation
Negative regulation of protein sumoylation
Negative regulation of protein ubiquitination
Negative regulation of reactive oxygen species biosynthetic process
Negative regulation of TRAIL-activated apoptotic signaling pathway
Negative regulation of ubiquitin-protein transferase activity
Negative regulation of ubiquitin-specific protease activity
Obsolete enzyme active site formation via L-cysteine sulfinic acid
Peptidyl-arginine deglycation
Peptidyl-cysteine deglycation
Peptidyl-lysine deglycation
Positive regulation of acute inflammatory response to antigenic stimulus
Positive regulation of androgen receptor activity
Positive regulation of autophagy of mitochondrion
Positive regulation of DNA-binding transcription factor activity
Positive regulation of dopamine biosynthetic process
Positive regulation of gene expression
Positive regulation of interleukin-8 production
Positive regulation of L-dopa biosynthetic process
Positive regulation of L-dopa decarboxylase activity
Positive regulation of mitochondrial electron transport, NADH to ubiquinone
Positive regulation of NAD(P)H oxidase activity
Positive regulation of oxidative phosphorylation uncoupler activity
Positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of protein homodimerization activity
Positive regulation of protein kinase B signaling
Positive regulation of protein localization to nucleus
Positive regulation of protein-containing complex assembly
Positive regulation of pyrroline-5-carboxylate reductase activity
Positive regulation of reactive oxygen species biosynthetic process
Positive regulation of superoxide dismutase activity
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription regulatory region DNA binding
Positive regulation of tyrosine 3-monooxygenase activity
Protein deglycation, glyoxal removal
Protein deglycation, methylglyoxal removal
Protein deglycosylation
Protein stabilization
Ras protein signal transduction
Regulation of androgen receptor signaling pathway
Regulation of histone acetylation
Regulation of histone ubiquitination
Regulation of inflammatory response
Regulation of mitochondrial membrane potential
Regulation of neuron apoptotic process
Regulation of supramolecular fiber organization
Single fertilization
Cellular Component
Adherens junction
Axon
Cell body
Cell-cell adherens junction
Chromatin
Cytoplasm
Cytosol
Endoplasmic reticulum
Extracellular exosome
Membrane raft
Mitochondrial intermembrane space
Mitochondrial matrix
Mitochondrion
Nucleoplasm
Nucleus
Obsolete cell
Perinuclear region of cytoplasm
Plasma membrane
PML body
Presynapse
Molecular Function
Androgen receptor binding
Cadherin binding
Copper ion binding
Cupric ion binding
Cuprous ion binding
Cytokine binding
Enzyme binding
Glyoxalase (glycolic acid-forming) activity
Glyoxalase III activity
Identical protein binding
Kinase binding
L-dopa decarboxylase activator activity
Mercury ion binding
MRNA binding
Oxidoreductase activity, acting on peroxide as acceptor
Oxygen sensor activity
Peptidase activity
Peroxiredoxin activity
Protein deglycase activity
Protein homodimerization activity
Protein-containing complex binding
Repressing transcription factor binding
Scaffold protein binding
Signaling receptor binding
Small protein activating enzyme binding
Superoxide dismutase copper chaperone activity
Transcription coactivator activity
Transcription factor binding
Tyrosine 3-monooxygenase activator activity
Ubiquitin-like protein conjugating enzyme binding
Ubiquitin-specific protease binding
The reference OMIM entry for this protein is 168600
Parkinson disease, late-onset; pd
Park
A number sign (#) is used with this entry because of evidence that late-onset or sporadic Parkinson disease (PD) can have more than one genetic and/or environmental cause.
DESCRIPTION
Parkinson disease was first described by James Parkinson in 1817. It is the second most common neurodegenerative disorder after Alzheimer disease (AD; 104300), affecting approximately 1% of the population over age 50 (Polymeropoulos et al., 1996). - Reviews Warner and Schapira (2003) reviewed the genetic and environmental causes of Parkinson disease. Feany (2004) reviewed the genetics of Parkinson disease and provided a speculative model of interactions among proteins implicated in PD. Lees et al. (2009) provided a review of Parkinson disease, with emphasis on diagnosis, neuropathology, and treatment. - Genetic Heterogeneity of Parkinson Disease Several loci for autosomal dominant Parkinson disease have been identified, including PARK1 (168601) and PARK4, caused by mutation in or triplication of the alpha-synuclein gene (SNCA; 163890), respectively, on 4q22.1; PARK5 (191342), caused by mutation in the UCHL1 gene on 4p14; PARK8 (607060), caused by mutation in the LRRK2 gene (609007) on 12q12; PARK11 (607688), caused by mutation in the GIGYF2 gene (612003) on 2q37; and PARK13 (610297), caused by mutation in the HTRA2 gene (606441) on 2p12; PARK17 (614203), caused by mutation in the VPS35 gene (601501) on 16q12; PARK18 (614251), caused by mutation in the EIF4G1 gene (600495) on 3q27; and PARK21 (616361), caused by mutation in the DNAJC13 gene (614334) on 3q22. Several loci for autosomal recessive early-onset Parkinson disease have been identified: PARK2 (600116), caused by mutation in the gene encoding parkin (PARK2; 602544) on 6q25.2-q27; PARK6 (605909), caused by mutation in the PINK1 gene (608309) on 1p36; PARK7 (606324), caused by mutation in the DJ1 gene (PARK7; 602533) on 1p36; PARK14 (612953), caused by mutation in the PLA2G6 gene (603604) on 22q13; PARK15 (260300), caused by mutation in the FBXO7 gene (605648) on 22q12-q13; PARK19 (615528), caused by mutation in the DNAJC6 gene (608375) on 1p32; and PARK20 (615530), caused by mutation in the SYNJ1 gene (604297) on 21q22. PARK3 (602404) has been mapped to chromosome 2p13; PARK10 (606852) has been mapped to chromosome 1p34-p32; PARK16 (613164) has been mapped to chromosome 1q32. A locus on the X chromosome has been identified (PARK12; 300557). There is also evidence that mitochondrial mutations may cause or contribute to Parkinson disease (see 556500). Susceptibility to the development of the more common late-onset form of Parkinson disease has been associated with polymorphisms or mutations in several genes, including GBA (606463), MAPT (157140), MC1R (155555), ADH1C (103730), and genes at the HLA locus (see, e.g., HLA-DRA, 142860). Each of these risk factors independently may have a modest effect on disease development, but together may have a substantial cumulative effect (Hamza et al., 2010). Susceptibility to PD may also be conferred by expanded trinucleotide repeats in several genes causing other neurologic disorders usually characterized by spinocerebellar ataxia (SCA), including the ATXN2 (601517), ATXN3 (607047), TBP (600075), and ATXN8OS (603680) genes.CLINICAL FEATURES
The diagnosis of classic idiopathic PD is primarily clinical, with manifestations including resting tremor, muscular rigidity, bradykinesia, and postural instability. Additional features are characteristi ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 168600 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed