PINK1

PINK1
Identifiants
Aliases	PINK1, PTEN-induced putative kinase 1
IDs externes	OMIM: 608309 MGI: 1916193 HomoloGene: 32672 GeneCards: PINK1
Position du gène (Homme) Chr. Chromosome 1 humain[1] Locus 1p36.12 Début 20,633,458 bp[1] Fin 20,651,511 bp[1]
Position du gène (Souris) Chr. Chromosome 4 (souris)[2] Locus 4|4 D3 Début 138,040,720 bp[2] Fin 138,053,618 bp[2]
Expression génétique Bgee Humain Souris (orthologue) Fortement exprimé dans tendon of biceps brachii muscle glutéal muscle gastrocnémien right frontal lobe cortex préfrontal amygdale muscle de la cuisse apex of heart putamen noyau accumbens Fortement exprimé dans muscle de la cuisse myocardium of ventricle muscle intercostal nerf ischiatique muscle digastrique muscle triceps brachial cheville muscle sterno-cléido-mastoïdien muscle temporal muscle extra-oculaire Plus de données d'expression de référence BioGPS Plus de données d'expression de référence
Gene Ontology Fonction moléculaire C3HC4-type RING finger domain binding activité kinase liaison ATP protein kinase activity liaison ion métal protein serine/threonine kinase activity calcium-dependent protein kinase activity peptidase activator activity magnesium ion binding activité de transférase liaison de protéase liaison protéique liaison nucléotide protein kinase B binding ubiquitin protein ligase binding Composant cellulaire cytoplasme cytosol membrane mitochondrial intermembrane space mitochondrie perinuclear region of cytoplasm cytosquelette noyau corps de Lewy integral component of mitochondrial outer membrane membrane mitochondrial externe chromatine TORC2 complex integral component of membrane ubiquitin ligase complex mitochondrial outer membrane translocase complex astrocyte projection axone cell body membrane mitochondriale interne cône de croissance Processus biologique negative regulation of neuron apoptotic process positive regulation of mitophagy in response to mitochondrial depolarization positive regulation of free ubiquitin chain polymerization regulation of protein ubiquitination cellular response to toxic substance positive regulation of catecholamine secretion regulation of synaptic vesicle transport positive regulation of translation phosphorylation des protéines positive regulation of dopamine secretion macroautophagy regulation of protein-containing complex assembly cellular response to hypoxia negative regulation of autophagosome assembly positive regulation of protein kinase B signaling positive regulation of protein dephosphorylation ubiquitin-dependent protein catabolic process peptidyl-serine autophosphorylation regulation of neuron apoptotic process response to oxidative stress negative regulation of gene expression positive regulation of peptidyl-serine phosphorylation negative regulation of mitochondrial fission positive regulation of mitochondrial electron transport, NADH to ubiquinone positive regulation of macroautophagy regulation of autophagy of mitochondrion positive regulation of ubiquitin-protein transferase activity negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway Ubiquitination negative regulation of oxidative stress-induced cell death negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide positive regulation of synaptic transmission, dopaminergic negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway regulation of oxidative phosphorylation regulation of mitochondrion organization regulation of hydrogen peroxide metabolic process negative regulation of oxidative stress-induced neuron death protein stabilization mitochondrion organization positive regulation of DNA-binding transcription factor activity negative regulation of autophagy of mitochondrion regulation of reactive oxygen species metabolic process positive regulation of ATP biosynthetic process maintenance of protein location in mitochondrion regulation of protein targeting to mitochondrion positive regulation of release of cytochrome c from mitochondria chaîne de transport d'électrons respiratoire positive regulation of protein ubiquitination regulation of proteasomal protein catabolic process activation of protein kinase B activity intracellular signal transduction negative regulation of macroautophagy positive regulation of protein targeting to mitochondrion positive regulation of cristae formation positive regulation of peptidase activity TORC2 signaling regulation of mitochondrial membrane potential autophagie negative regulation of JNK cascade establishment of protein localization to mitochondrion mitophagie peptidyl-serine phosphorylation positive regulation of I-kappaB kinase/NF-kappaB signaling cellular response to oxidative stress negative regulation of reactive oxygen species metabolic process negative regulation of apoptotic process positive regulation of protein phosphorylation positive regulation of histone deacetylase activity mitochondrion to lysosome transport regulation of cellular response to oxidative stress response to ischemia positive regulation of mitochondrial fission positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization cellular response to hydrogen sulfide phosphorylation negative regulation of neuron death positive regulation of NMDA glutamate receptor activity negative regulation of intrinsic apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologues Espèces Homme Souris Entrez 65018 68943 Ensembl ENSG00000158828 ENSMUSG00000028756 UniProt Q9BXM7 Q99MQ3 RefSeq (mRNA) NM_032409 NM_026880 RefSeq (protéine) NP_115785 NP_081156 Localisation (UCSC) Chr 1: 20.63 – 20.65 Mb Chr 4: 138.04 – 138.05 Mb Publication PubMed [3] [4]
Wikidata
Voir/Editer Humain Voir/Editer Souris

PINK1 (pour « PTEN-induced putative kinase 1 ») est une kinase mitrochondriale dont le gène est le PINK1 situé sur le chromosome 1 humain.

Rôles

Il joue un rôle important dans l'homéostasie des mitochondries[5] en intervenant dans l'autophagie de ces dernières[6]. Il intervient également dans l'intégrité de la chaîne de transport d'électrons[7]. Il intervient ainsi dans plusieurs tissus, dont les neurones mais aussi le muscle cardiaque[8] et le poumon, protégeant ce dernier de la fibrose pulmonaire[9].

En médecine

La mutation du PINK1 est responsable d'une forme précoce et familiale de maladie de Parkinson[10], appelée « maladie de Parkinson de type 6 » ou PARK6. La forme inactive du PINK1 entraîne une altération des mitochondries des neurones dopaminergiques et une concentration augmentée en dérivés réactifs de l'oxygène[11] qui est délétère pour la cellule.

Notes et références

1. GRCh38: Ensembl release 89: ENSG00000158828 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028756 - Ensembl, May 2017
3. « Publications PubMed pour l'Homme », sur National Center for Biotechnology Information, U.S. National Library of Medicine
4. « Publications PubMed pour la Souris », sur National Center for Biotechnology Information, U.S. National Library of Medicine
5. (en) Chu CT, « A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease » Hum Mol Genet. 2010;19:R28–37
6. (en) Narendra D, Walker JE, Youle R, « Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism » Cold Spring Harb Perspect Biol. 2012;4:a011338
7. (en) Liu W, Acin-Perez R, Geghman KD, Manfredi G, Lu B, Li C, « Pink1 regulates the oxidative phosphorylation machinery via mitochondrial fission » Proc Natl Acad Sci U S A. 2011;108:12920–12924
8. (en) Billia F, Hauck L, Konecny F, Rao V, Shen J, Mak TW, « PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function » Proc Natl Acad Sci U S A. 2011;108:9572–9577.
9. (en) Bueno M, Lai YC, Romero Y. et al. « PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis » J Clin Invest. 2014
10. (en) Valente EM, Abou-Sleiman PM, Caputo V. et al. « Hereditary early-onset Parkinson’s disease caused by mutations in PINK1 » Science 2004;304:1158–1160
11. (en) Wang HL, Chou AH, Wu AS. et al. « PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons » Biochim Biophys Acta. 2011;1812:674–684