PTEN Induced Putative Kinase 1 (PINK1)

BRPK; PARK6; Parkinson Disease(Autosomal Recessive)6; Serine/threonine-protein kinase PINK1, mitochondrial

SPN	N330
HGNC	14581
MGI	1916193
PubMed	19692353
RGD	1305769
UniProt	Q9BXM7
Wiki	PINK1

PINK1 encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease.

The protein shares 43% and 31% sequence identity with Drosophila CG4523 and C. elegans EEED8.9, respectively. Northern blot analysis detected ubiquitous expression of a 2.7-kb transcript, with highest expression in heart, skeletal muscle, and testis. RT-PCR analysis showed that expression of PINK1 was decreased in ovarian tumors compared with corresponding normal tissues.

Reference

"Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway."
Oncogene 20:4457-4465(2001) [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 biological annotation of human chromosome 1."
Nature 441:315-321(2006) [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] and Lung.

"The kinase domain of mitochondrial PINK1 faces the cytoplasm."
Proc. Natl. Acad. Sci. U.S.A. 105:12022-12027(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]

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

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

"PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria."
Nat. Commun. 3:1016-1016(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]

"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]

"PINK1 mutations are associated with sporadic early-onset parkinsonism."
Ann. Neurol. 56:336-341(2004) [PubMed] [Europe PMC] [Abstract]

"Novel PINK1 mutations in early-onset parkinsonism."
Ann. Neurol. 56:424-427(2004) [PubMed] [Europe PMC] [Abstract]

Erratum
Ann. Neurol. 56:603-603(2004)

"Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease."
Arch. Neurol. 61:1898-1904(2004) [PubMed] [Europe PMC] [Abstract]

"PINK1 (PARK6) associated Parkinson disease in Ireland."
Neurology 63:1486-1488(2004) [PubMed] [Europe PMC] [Abstract]

"Hereditary early-onset Parkinson's disease caused by mutations in PINK1."
Science 304:1158-1160(2004) [PubMed] [Europe PMC] [Abstract]

"Analysis of PINK1 in Asian patients with familial parkinsonism."
Clin. Genet. 68:468-470(2005) [PubMed] [Europe PMC] [Abstract]

"PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism."
Eur. J. Hum. Genet. 13:1086-1093(2005) [PubMed] [Europe PMC] [Abstract]

"Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism."
Hum. Mol. Genet. 14:3477-3492(2005) [PubMed] [Europe PMC] [Abstract]

"Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism."
Neurology 64:1955-1957(2005) [PubMed] [Europe PMC] [Abstract]

"Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes."
Neurology 65:87-95(2005) [PubMed] [Europe PMC] [Abstract]

"A heterozygous effect for PINK1 mutations in Parkinson's disease?"
Ann. Neurol. 60:414-419(2006) [PubMed] [Europe PMC] [Abstract]

"Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1."
Arch. Neurol. 63:1257-1261(2006) [PubMed] [Europe PMC] [Abstract]

"T313M PINK1 mutation in an extended highly consanguineous Saudi family with early-onset Parkinson disease."
Arch. Neurol. 63:1483-1485(2006) [PubMed] [Europe PMC] [Abstract]

"Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa."
Brain 129:686-694(2006) [PubMed] [Europe PMC] [Abstract]

"Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease."
Hum. Mol. Genet. 15:1816-1825(2006) [PubMed] [Europe PMC] [Abstract]

"PINK1 mutations in sporadic early-onset Parkinson's disease."
Mov. Disord. 21:789-793(2006) [PubMed] [Europe PMC] [Abstract]

"Analysis of the PINK1 gene in a cohort of patients with sporadic early-onset parkinsonism in Taiwan."
Neurosci. Lett. 394:33-36(2006) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum."
Hum. Mutat. 29:565-565(2008) [PubMed] [Europe PMC] [Abstract]

"Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation."
J. Neurol. 255:643-648(2008) [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]