Parkine

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
Alias	PRKN
IDs externes	OMIM: 602544 MGI: 1355296 HomoloGene: 3355 GeneCards: PRKN
Position du gène (humain)
Chr.	Chromosome 6 humain
Fin	162,727,775 bp
Position du gène (souris)
Chr.	Chromosome 17 (souris)
Fin	12,282,248 bp
Expression génique
	Fortement exprimé dans
	nerf sural; ; testicule; ; muscle de la cuisse; ; sperme; ; tendon calcanéen; ; muscle gastrocnémien; ; gonade; ; cortex préfrontal; ; auricule de l'oreillette droite; ; left testis;
	Fortement exprimé dans
	muscle de la cuisse; ; embryon; ; spermatocyte; ; embryon; ; spermatide; ; zygote; ; muscle soléaire; ; articulation du genou; ; morula; ; right kidney;
	Plus de données d'expression de référence
	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
	5071
	50873
	ENSG00000185345
	ENSMUSG00000023826
	O60260
	Q9WVS6
	NM_004562; NM_013987; NM_013988
	NM_016694; NM_001317726
	NP_004553; NP_054642; NP_054643
	NP_001304655; NP_057903
	Wikidata
Voir/Editer Humain	Voir/Editer Souris

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

Rôles

Comme ubiquitine ligase, elle facilite la dégradation des protéines par le protéasome. Elle contribue à maintenir l'intégrité de la membrane mitochondriale^[5] en association avec le PINK1^[6], ce dernier activant la parkine par l'intermédiaire d'une phosphorylation de l'ubiquitine^[7].

Elle empêche également l'internalisation du récepteur de l'EGF et active la voie du phosphoinositide 3-kinase/Atk^[8].

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^[9].

Notes et références

↑ ^{a b et c} GRCh38: Ensembl release 89: ENSG00000185345 - Ensembl, May 2017
↑ ^{a b et c} GRCm38: Ensembl release 89: ENSMUSG00000023826 - Ensembl, May 2017
↑ « Publications PubMed pour l'Homme », sur National Center for Biotechnology Information, U.S. National Library of Medicine
↑ « Publications PubMed pour la Souris », sur National Center for Biotechnology Information, U.S. National Library of Medicine
↑ Corti O, Brice A, Mitochondrial quality control turns out to be the principal suspect in parkin and PINK1-related autosomal recessive Parkinson’s disease, Curr Opin Neurobiol, 2013;23:100–108
↑ Pilsl A, Winklhofer KF, Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson’s disease, Acta Neuropathol, 2012;123:173–188
↑ Koyano F1, Okatsu K1, Kosako H et al. Ubiquitin is phosphorylated by PINK1 to activate parkin, Nature, 2014;510:162–166.
↑ Fallon L1, Bélanger CM, Corera AT et al. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling, Nat Cell Biol, 2006;8:834–842
↑ Yamada M, Mizuno Y, Mochizuki H, Parkin gene therapy for α-synucleinopathy: a rat model of Parkinson’s disease, Hum Gene Ther, 2005;16:262–270

[refGRCh38Ensembl-1] {a b et c} GRCh38: Ensembl release 89: ENSG00000185345 - Ensembl, May 2017

[refGRCm38Ensembl-2] {a b et c} GRCm38: Ensembl release 89: ENSMUSG00000023826 - 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

[Corti_2013-5] Corti O, Brice A, Mitochondrial quality control turns out to be the principal suspect in parkin and PINK1-related autosomal recessive Parkinson’s disease, Curr Opin Neurobiol, 2013;23:100–108

[Pilsl_2012-6] Pilsl A, Winklhofer KF, Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson’s disease, Acta Neuropathol, 2012;123:173–188

[Koyano_2014-7] Koyano F1, Okatsu K1, Kosako H et al. Ubiquitin is phosphorylated by PINK1 to activate parkin, Nature, 2014;510:162–166.

[Fallon_2006-8] Fallon L1, Bélanger CM, Corera AT et al. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling, Nat Cell Biol, 2006;8:834–842

[Yamada_2005-9] Yamada M, Mizuno Y, Mochizuki H, Parkin gene therapy for α-synucleinopathy: a rat model of Parkinson’s disease, Hum Gene Ther, 2005;16:262–270

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v · m Chromosome 6 humain
Gènes	ALDH5A1 COL9A1 COL10A1 COL11A2 COL12A1 COL19A1 COL21A1 HLA-B HLA-DQ2 PEX7 SLC16A10 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC18B1 SLC22A16 SLC22A1 SLC22A23 SLC22A2 SLC22A3 SLC22A7 SLC25A27 SLC26A8 SLC29A1 SLC2A12 SLC35A1 SLC35B2 SLC35B3 SLC35D3 SLC35F1 SLC39A7 SLC44A4 STX11
Protéines	21-Hydroxylase Énoyl-coenzyme A-isomérase Facteur de nécrose tumorale Facteur XIII Importine alpha OR10C1 Parkine Pepsinogène Phosphoglycérate-kinase POLH Ribonucléase T2 Synthase de GMP-AMP cyclique Utrophine
Maladies liées	Acidurie 4-hydroxybutyrique Argininémie Ataxie spinocérébelleuse Chondrodysplasie métaphysaire type Schmid Chondrodysplasie ponctuée type rhizomélique (Type 1) Diabète néonatal Diabète néonatal transitoire Dysplasie cléidocrânienne Hyperplasie congénitale des surrénales Hémochromatose de type 1 Lymphohistiocytose familiale Lymphohistiocytose hémophagocytaire Maladie cœliaque Maladie génétique du métabolisme des métaux Maladie de Nasu-Hakola Maladie de Refsum Maladie de Stargardt Maladies de surcharge en acide sialique libre Polykystose rénale autosomique récessive Spondylarthrite ankylosante Surdité d'origine génétique Syndrome de Char Syndrome de Joubert Syndrome de Lafora Syndrome de Yunis-Varon Trouble du spectre de l'autisme

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Parkine

Rôles

En médecine

Notes et références

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