Parkine

La parkine est une enzyme de type ubiquitine ligase dont le gène, PARK2, est situé sur le chromosome 6 humain.

PARK2
Structure de la protéine PARK2. Basé sur l'identifiant PDB 1iyf.
Structures disponibles PDB Recherche d'orthologue: PDBe RCSB Identifiants PDB 1IYF, 2JMO, 4I1F, 4I1H, 4BM9, 5C1Z, 5C23, 5C9V
Identifiants
Aliases	PRKN
IDs externes	OMIM: 602544 MGI: 1355296 HomoloGene: 3355 GeneCards: PRKN
Position du gène (Homme) Chr. Chromosome 6 humain Locus 6q26 Début 161,347,417 bp Fin 162,727,775 bp
Position du gène (Souris) Chr. Chromosome 17 (souris) Locus 17 A1|17 7.8 cM Début 11,059,271 bp Fin 12,282,248 bp
Expression génétique Bgee Humain Souris (orthologue) Fortement exprimé dans nerf sural sperme tendon calcanéen muscle gastrocnémien cortex préfrontal ventricule gauche gyrus cingulaire Brodmann area 9 noyau accumbens artère poplitée Fortement exprimé dans spermatocyte spermatide muscle soléaire articulation du genou morula skeletal muscle tissue secondary oocyte proximal tubule tube séminifère gyrus frontal supérieur Plus de données d'expression de référence BioGPS Plus de données d'expression de référence
Gene Ontology Fonction moléculaire liaison de phospholipase DNA-binding transcription factor activity SH3 domain binding liaison d'histone déacétylase tubulin binding cullin family protein binding PDZ domain binding heat shock protein binding liaison ion métal Hsp70 protein binding liaison de kinase liaison enzymatique beta-catenin binding zinc ion binding liaison protéique ubiquitin conjugating enzyme binding protein kinase binding chaperone binding transcription cis-regulatory region binding ubiquitin-protein transferase activity F-box domain binding ubiquitin binding identical protein binding actin binding ubiquitin-specific protease binding G protein-coupled receptor binding ubiquitin protein ligase binding activité de transférase ubiquitin protein ligase activity DNA-binding transcription repressor activity, RNA polymerase II-specific liaison de complexe macromoléculaire Composant cellulaire cytoplasme cytosol mitochondrie perinuclear region of cytoplasm noyau corps de Lewy SCF ubiquitin ligase complex aggresome réticulum endoplasmique appareil de Golgi Parkin-FBXW7-Cul1 ubiquitin ligase complex ubiquitin ligase complex LUBAC complex présynapse neuron projection mitochondrion-derived vesicle nuclear speck complexe macromoléculaire Processus biologique negative regulation of neuron apoptotic process protein K29-linked ubiquitination negative regulation of insulin secretion ERAD pathway positive regulation of mitochondrial fission positive regulation of mitophagy in response to mitochondrial depolarization positive regulation of protein catabolic process synaptic transmission, glutamatergic positive regulation of tumor necrosis factor-mediated signaling pathway neuron cellular homeostasis regulation of protein ubiquitination cellular response to toxic substance modulation of chemical synaptic transmission regulation of synaptic vesicle transport apprentissage protein monoubiquitination synaptic transmission, dopaminergic positive regulation of neurotransmitter uptake regulation of glucose metabolic process protein K6-linked ubiquitination negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator negative regulation of spontaneous neurotransmitter secretion negative regulation by host of viral genome replication positive regulation of DNA binding macroautophagy negative regulation of canonical Wnt signaling pathway Unfolded Protein Response aggresome assembly proteasome-mediated ubiquitin-dependent protein catabolic process regulation of dopamine secretion zinc ion homeostasis free ubiquitin chain polymerization regulation of transcription, DNA-templated locomotory behavior norepinephrine metabolic process negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway adult locomotory behavior protein metabolic process negative regulation of cell death response to oxidative stress protein K27-linked ubiquitination negative regulation of gene expression transcription, DNA-templated response to endoplasmic reticulum stress protein K11-linked ubiquitination central nervous system development negative regulation of oxidative stress-induced cell death positive regulation of mitochondrial fusion protein localization to mitochondrion proteasomal protein catabolic process cellular response to manganese ion negative regulation of mitochondrial fusion protein autoubiquitination negative regulation of neuron death negative regulation of protein phosphorylation negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway negative regulation of primary amine oxidase activity réflexe de sursaut acoustique mitochondrial fission regulation of mitochondrion organization regulation of canonical Wnt signaling pathway negative regulation of release of cytochrome c from mitochondria protein stabilization mitochondrion organization protein polyubiquitination negative regulation of transcription by RNA polymerase II regulation of reactive oxygen species metabolic process regulation of neurotransmitter secretion positive regulation of protein linear polyubiquitination protein K48-linked ubiquitination dopamine uptake involved in synaptic transmission regulation of autophagy regulation of protein targeting to mitochondrion protein destabilization negative regulation of glucokinase activity positive regulation of proteasomal protein catabolic process protein K63-linked ubiquitination cellular response to dopamine regulation of lipid transport negative regulation of actin filament bundle assembly regulation of dopamine metabolic process regulation of mitochondrial membrane potential autophagie negative regulation of JNK cascade dopamine metabolic process positive regulation of gene expression positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of dendrite extension negative regulation of reactive oxygen species metabolic process positive regulation of transcription by RNA polymerase II mitophagy Ubiquitination parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization positive regulation of proteasomal ubiquitin-dependent protein catabolic process protein deubiquitination regulation of protein stability positive regulation of protein binding mitochondrion to lysosome transport regulation of cellular response to oxidative stress negative regulation of exosomal secretion positive regulation of retrograde transport, endosome to Golgi negative regulation of intralumenal vesicle formation positive regulation of protein localization to membrane mitophagie negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway positive regulation of autophagy of mitochondrion ubiquitin-dependent protein catabolic process regulation of apoptotic process Sources:Amigo / QuickGO
Orthologues Espèces Homme Souris Entrez 5071 50873 Ensembl ENSG00000185345 ENSMUSG00000023826 UniProt O60260 Q9WVS6 RefSeq (mRNA) NM_004562 NM_013987 NM_013988 NM_016694 NM_001317726 RefSeq (protéine) NP_004553 NP_054642 NP_054643 NP_001304655 NP_057903 Localisation (UCSC) Chr 6: 161.35 – 162.73 Mb Chr 17: 11.06 – 12.28 Mb Publication PubMed
Wikidata
Voir/Editer Humain Voir/Editer Souris

Rôles

Comme ubiquitine ligase, elle facilite la dégradation des protéines par le protéasome. Elle contribue à maintenir l'intégrité de la membrane mitochondriale en association avec le PINK1, ce dernier activant la parkine par l'intermédiaire d'une phosphorylation de l'ubiquitine.

Elle empêche également l'internalisation du récepteur de l'EGF et active la voie du phosphoinositide 3-kinase/Atk.

En médecine

La mutation du gène entraîne une syndrome parkinsonien avec une transmission autosomale récessive. Ce gène constitue ainsi une piste de recherche pour la thérapie génique de la maladie de Parkinson.