Parkinson Disease Protein 2 (PARK2)

AR-JP; LPRS2; PDJ; PRKN; Parkin; Autosomal Recessive,Juvenile; E3 ubiquitin-protein ligase parkin

SPN	N328
HGNC	8607
MGI	1355296
PubMed	22956510
RGD	61797
UniProt	O60260
Wiki	Parkin

Parkin is a proteinencoded by the PARK2 gene.The precise function of this protein is unknown; however, the protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinson disease.

PARK2 is the parkin gene that may cause a form of autosomal recessive juvenile Parkinson disease due to a mutation in the parkin protein. This form of genetic mutation may be one of the most common known genetic causes of early-onset Parkinson disease.

Reference

"Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism."
Nature 392:605-608(1998) [PubMed] [Europe PMC] [Abstract]

"Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood."
Neurosci. Lett. 460:196-200(2009) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and analysis of human chromosome 6."
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients."
Ann. Neurol. 45:668-672(1999) [PubMed] [Europe PMC] [Abstract]

"Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity."
J. Biol. Chem. 275:35661-35664(2000) [PubMed] [Europe PMC] [Abstract]

"Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase."
Nat. Genet. 25:302-305(2000) [PubMed] [Europe PMC] [Abstract]

"Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1."
Proc. Natl. Acad. Sci. U.S.A. 97:13354-13359(2000) [PubMed] [Europe PMC] [Abstract]

"An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin."
Cell 105:891-902(2001) [PubMed] [Europe PMC] [Abstract]

"Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease."
Nat. Med. 7:1144-1150(2001) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease."
Science 293:263-269(2001) [PubMed] [Europe PMC] [Abstract]

"Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily."
Mol. Biol. Evol. 19:2039-2050(2002) [PubMed] [Europe PMC] [Abstract]

"CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity."
Mol. Cell 10:55-67(2002) [PubMed] [Europe PMC] [Abstract]

"The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI."
Hum. Mol. Genet. 12:2587-2597(2003) [PubMed] [Europe PMC] [Abstract]

"A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death."
J. Biol. Chem. 278:51901-51910(2003) [PubMed] [Europe PMC] [Abstract]

"Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity."
Neuron 37:735-749(2003) [PubMed] [Europe PMC] [Abstract]

"Alterations in the common fragile site gene Parkin in ovarian and other cancers."
Oncogene 22:8370-8378(2003) [PubMed] [Europe PMC] [Abstract]

"Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27."
Proc. Natl. Acad. Sci. U.S.A. 100:5956-5961(2003) [PubMed] [Europe PMC] [Abstract]

"How does parkin ligate ubiquitin to Parkinson's disease?"
EMBO Rep. 5:681-685(2004) [PubMed] [Europe PMC] [Abstract]

"S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function."
Science 304:1328-1331(2004) [PubMed] [Europe PMC] [Abstract]

"Parkin interacts with the proteasome subunit alpha4."
FEBS Lett. 579:3913-3919(2005) [PubMed] [Europe PMC] [Abstract]

"Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation."
J. Neurosci. 25:2002-2009(2005) [PubMed] [Europe PMC] [Abstract]

"Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death."
J. Neurosci. 25:7968-7978(2005) [PubMed] [Europe PMC] [Abstract]

"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]

"Parkin ubiquitinates and promotes the degradation of RanBP2."
J. Biol. Chem. 281:3595-3603(2006) [PubMed] [Europe PMC] [Abstract]

"Functional modulation of parkin through physical interaction with SUMO-1."
J. Neurosci. Res. 84:1543-1554(2006) [PubMed] [Europe PMC] [Abstract]

"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6."
J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract]

"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy."
J. Cell Biol. 183:795-803(2008) [PubMed] [Europe PMC] [Abstract]

"Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress."
Neurosci. Lett. 440:4-8(2008) [PubMed] [Europe PMC] [Abstract]

"Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation."
J. Clin. Invest. 119:650-660(2009) [PubMed] [Europe PMC] [Abstract]

"Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease."
Nat. Cell Biol. 11:1370-1375(2009) [PubMed] [Europe PMC] [Abstract]

"The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations."
Autophagy 6:871-878(2010) [PubMed] [Europe PMC] [Abstract]

"Parkin mono-ubiquitinates Bcl-2 and regulates autophagy."
J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract]

"PINK1-dependent recruitment of Parkin to mitochondria in mitophagy."
Proc. Natl. Acad. Sci. U.S.A. 107:378-383(2010) [PubMed] [Europe PMC] [Abstract]

"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease."
Cell 144:689-702(2011) [PubMed] [Europe PMC] [Abstract]

"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids."
Nature 474:105-108(2011) [PubMed] [Europe PMC] [Abstract]

"Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential."
Hum. Mol. Genet. 21:991-1003(2012) [PubMed] [Europe PMC] [Abstract]

"Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation."
J. Biol. Chem. 288:22019-22032(2013) [PubMed] [Europe PMC] [Abstract]

"The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy."
Nat. Neurosci. 16:1257-1265(2013) [PubMed] [Europe PMC] [Abstract]

"High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy."
Nature 504:291-295(2013) [PubMed] [Europe PMC] [Abstract]

"PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria."
Science 340:471-475(2013) [PubMed] [Europe PMC] [Abstract]

"Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65."
Biochem. J. 460:127-139(2014) [PubMed] [Europe PMC] [Abstract]

"PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity."
J. Cell Biol. 205:143-153(2014) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin is phosphorylated by PINK1 to activate parkin."
Nature 510:162-166(2014) [PubMed] [Europe PMC] [Abstract]

"The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy."
Nature 510:370-375(2014) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis."
EMBO J. 34:307-325(2015) [PubMed] [Europe PMC] [Abstract]

"USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria."
Nat. Cell Biol. 17:160-169(2015) [PubMed] [Europe PMC] [Abstract]

"Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain."
EMBO Rep. 4:301-306(2003) [PubMed] [Europe PMC] [Abstract]

"Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease."
Proc. Natl. Acad. Sci. U.S.A. 104:3095-3100(2007) [PubMed] [Europe PMC] [Abstract]

"Structure of the human Parkin ligase domain in an autoinhibited state."
EMBO J. 32:2099-2112(2013) [PubMed] [Europe PMC] [Abstract]

"Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases."
Nat. Commun. 4:1982-1982(2013) [PubMed] [Europe PMC] [Abstract]

"Parkin genetics: one model for Parkinson's disease."
Hum. Mol. Genet. 13:R127-R133(2004) [PubMed] [Europe PMC] [Abstract]

"Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene."
Biochem. Biophys. Res. Commun. 249:754-758(1998) [PubMed] [Europe PMC] [Abstract]

Erratum
Biochem. Biophys. Res. Commun. 251:666-666(1998)

"A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe."
Hum. Mol. Genet. 8:567-574(1999) [PubMed] [Europe PMC] [Abstract]

"Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson's disease."
NeuroReport 10:2735-2739(1999) [PubMed] [Europe PMC] [Abstract]

"Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism."
Ann. Neurol. 48:245-250(2000) [PubMed] [Europe PMC] [Abstract]

"Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in Taiwan."
Eur. Neurol. 44:90-93(2000) [PubMed] [Europe PMC] [Abstract]

"Association between early-onset Parkinson's disease and mutations in the parkin gene."
N. Engl. J. Med. 342:1560-1567(2000) [PubMed] [Europe PMC] [Abstract]

"Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects."
Am. J. Hum. Genet. 68:617-626(2001) [PubMed] [Europe PMC] [Abstract]

"The importance of gene dosage studies: mutational analysis of the parkin gene in early-onset parkinsonism."
Hum. Mol. Genet. 10:1649-1656(2001) [PubMed] [Europe PMC] [Abstract]

"A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile parkinsonism in a population from North West Colombia."
Neurosci. Lett. 298:87-90(2001) [PubMed] [Europe PMC] [Abstract]

"Complex relationship between parkin mutations and Parkinson disease."
Am. J. Med. Genet. 114:584-591(2002) [PubMed] [Europe PMC] [Abstract]

Erratum
Am. J. Med. Genet. 114:992-992(2002)

"Role of parkin mutations in 111 community-based patients with early-onset parkinsonism."
Ann. Neurol. 51:621-625(2002) [PubMed] [Europe PMC] [Abstract]

"Molecular findings in familial Parkinson disease in Spain."
Arch. Neurol. 59:966-970(2002) [PubMed] [Europe PMC] [Abstract]

"Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families."
J. Med. Genet. 39:489-492(2002) [PubMed] [Europe PMC] [Abstract]

"Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism."
J. Neurol. Neurosurg. Psych. 73:582-584(2002) [PubMed] [Europe PMC] [Abstract]

"Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations."
Neurology 58:1239-1246(2002) [PubMed] [Europe PMC] [Abstract]

"A new point mutation on exon 2 of parkin gene in Parkinson's disease."
Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:409-411(2002) [PubMed] [Europe PMC] [Abstract]

"Parkin mutations and susceptibility alleles in late-onset Parkinson's disease."
Ann. Neurol. 53:624-629(2003) [PubMed] [Europe PMC] [Abstract]

"Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease."
Neurology 60:796-801(2003) [PubMed] [Europe PMC] [Abstract]

"Parkin mutations are rare in patients with young-onset parkinsonism in a US population."
Parkinsonism Relat. Disord. 9:309-312(2003) [PubMed] [Europe PMC] [Abstract]

"Novel parkin mutations detected in patients with early-onset Parkinson's disease."
Mov. Disord. 20:424-431(2005) [PubMed] [Europe PMC] [Abstract]

"PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy."
J. Cell Biol. 189:211-221(2010) [PubMed] [Europe PMC] [Abstract]

"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]