Razlikovati: Parkin (čvor).
Parkin je protein koji je kod ljudi kodiran genom PARK2.
To je E3 ubikvitin-ligaza od 465 ostataka koji ima kritičnu ulogu u ubikvitinaciji – procesu kojim su molekule kovalentno povezane sa ubikvitinom (Ub) i usmjerene prema razgradnji u proteasomima ili lizosomima. Ubikvitinacija uključuje uzastopno djelovanje tri enzima. E1 enzim koji aktivira ubikvitin u eukariotskim ćelijama veže se za neaktivni Ub putem tioesterskih veza i mobilizira ga u procesu ovisnom o ATP-u. (2) Ub se zatim prenosi u E2 enzim koji konjuguje ubikvitin prije nego što se konjugira sa ciljnim proteinom preko E3 ubikvitin-ligaza.[5] Postoji mnoštvo E3 ligaza, koje se razlikuju po strukturi i specifičnosti supstrat, kako bi omogućile selektivno ciljanje proteina za unutarćelijsku degradaciju.
Kratke činjenice PRKN, Dostupne strukture ...
PRKN |
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Identifikatori |
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Aliasi | PRKN |
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Vanjski ID-jevi | OMIM: 602544 MGI: 1355296 HomoloGene: 3355 GeneCards: PRKN |
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Ontologija gena |
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Molekularna funkcija | • phospholipase binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • SH3 domain binding • histone deacetylase binding • vezivanje tubulina • cullin family protein binding • PDZ domain binding • heat shock protein binding • vezivanje iona metala • Hsp70 protein binding • kinase binding • vezivanje enzima • beta-catenin binding • vezivanje iona cinka • GO:0001948, GO:0016582 vezivanje za proteine • ubiquitin conjugating enzyme binding • protein kinase binding • chaperone binding • GO:0000975 transcription cis-regulatory region binding • GO:0050372 aktivnost sa transferazom ubikvitina • F-box domain binding • ubiquitin binding • vezivanje identičnih proteina • actin binding • ubiquitin-specific protease binding • G protein-coupled receptor binding • ubiquitin protein ligase binding • aktivnost sa transferazom • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • GO:0032403 protein-containing complex binding
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Ćelijska komponenta | • citoplazma • citosol • mitohondrija • perinuklearno područje citoplazme • jedro • Lewy body • SCF ubiquitin ligase complex • aggresome • Endoplazmatski retikulum • Golđijev aparat • Parkin-FBXW7-Cul1 ubiquitin ligase complex • kompleks ubikvitin-ligaze • LUBAC complex • presynapse • neuron projection • mitochondrion-derived vesicle • nuclear speck • GO:0009327 makromolekulani kompleks
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Biološki proces | • GO:1904089 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 • GO:1903364 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 • Učenje • 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 • GO:0009373 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 • GO:0044267 protein metabolic process • negative regulation of cell death • GO:0001306 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 • GO:0033128 negative regulation of protein phosphorylation • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • negative regulation of primary amine oxidase activity • startle response • 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 • GO:1901227 negative regulation of transcription by RNA polymerase II • GO:1904489 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 • Autofagija • negative regulation of JNK cascade • dopamine metabolic process • GO:1901313 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 • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • mitophagy • protein 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 • autophagy of mitochondrion • 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
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Izvori:Amigo / QuickGO |
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Ortolozi |
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Vrste | Čovjek | Miš |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNK) | | |
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RefSeq (bjelančevina) | | |
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Lokacija (UCSC) | Chr 6: 161.35 – 162.73 Mb | Chr 17: 11.06 – 12.28 Mb |
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PubMed pretraga | [3] | [4] |
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Wikipodaci |
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Zatvori
Konkretno, parkin prepoznaje proteine na vanjskoj membrani mitohondrija nakon povede ćelija i posreduje u čišćenju oštećenih mitohondrija putem autofagije i proteasomskih mehanizama.[6] Parkin također poboljšava preživljavanje ćelija suzbijanjem mitohondrijski ovisnih i neovisnih apoptoza. Mutacije povezane su s mitohondrijskom disfunkcijom, što dovodi do neuronske smrti u Parkinsonovoj bolesti [7] iporemećenog metabolizma i tumorigenezi.[8]