PRKN report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_1903265Biological processpositive regulation of tumor necrosis factor-mediated signaling pathway
GO_0010821Biological processregulation of mitochondrion organization
GO_0070585Biological processprotein localization to mitochondrion
GO_1903377Biological processnegative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO_1903382Biological processnegative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway
GO_0016236Biological processmacroautophagy
GO_0090090Biological processnegative regulation of canonical Wnt signaling pathway
GO_0046676Biological processnegative regulation of insulin secretion
GO_0010994Biological processfree ubiquitin chain polymerization
GO_0061734Biological processparkin-mediated stimulation of mitophagy in response to mitochondrial depolarization
GO_0001933Biological processnegative regulation of protein phosphorylation
GO_0099074Biological processmitochondrion to lysosome vesicle-mediated transport
GO_0050821Biological processprotein stabilization
GO_0046329Biological processnegative regulation of JNK cascade
GO_1901526Biological processpositive regulation of mitophagy
GO_0007417Biological processcentral nervous system development
GO_0010637Biological processnegative regulation of mitochondrial fusion
GO_1902283Biological processnegative regulation of primary amine oxidase activity
GO_1905366Biological processnegative regulation of intralumenal vesicle formation
GO_0001964Biological processstartle response
GO_0000423Biological processmitophagy
GO_0042415Biological processnorepinephrine metabolic process
GO_0006979Biological processresponse to oxidative stress
GO_0060828Biological processregulation of canonical Wnt signaling pathway
GO_0043161Biological processproteasome-mediated ubiquitin-dependent protein catabolic process
GO_0014059Biological processregulation of dopamine secretion
GO_0098779Biological processpositive regulation of mitophagy in response to mitochondrial depolarization
GO_1903351Biological processcellular response to dopamine
GO_1901800Biological processpositive regulation of proteasomal protein catabolic process
GO_0000209Biological processprotein polyubiquitination
GO_1902236Biological processnegative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO_0010629Biological processnegative regulation of gene expression
GO_0007612Biological processlearning
GO_0034976Biological processresponse to endoplasmic reticulum stress
GO_0032436Biological processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO_0010628Biological processpositive regulation of gene expression
GO_0051865Biological processprotein autoubiquitination
GO_0042417Biological processdopamine metabolic process
GO_0071287Biological processcellular response to manganese ion
GO_0031396Biological processregulation of protein ubiquitination
GO_0045732Biological processpositive regulation of protein catabolic process
GO_0042981Biological processregulation of apoptotic process
GO_0010506Biological processregulation of autophagy
GO_1902254Biological processnegative regulation of intrinsic apoptotic signaling pathway by p53 class mediator
GO_0070534Biological processprotein K63-linked ubiquitination
GO_1904049Biological processnegative regulation of spontaneous neurotransmitter secretion
GO_0000422Biological processautophagy of mitochondrion
GO_0085020Biological processprotein K6-linked ubiquitination
GO_0016567Biological processprotein ubiquitination
GO_2000377Biological processregulation of reactive oxygen species metabolic process
GO_0034620Biological processcellular response to unfolded protein
GO_0070979Biological processprotein K11-linked ubiquitination
GO_0010498Biological processproteasomal protein catabolic process
GO_0032092Biological processpositive regulation of protein binding
GO_0090201Biological processnegative regulation of release of cytochrome c from mitochondria
GO_0060544Biological processregulation of necroptotic process
GO_0006511Biological processubiquitin-dependent protein catabolic process
GO_0044828Biological processnegative regulation by host of viral genome replication
GO_0031648Biological processprotein destabilization
GO_0034599Biological processcellular response to oxidative stress
GO_0007005Biological processmitochondrion organization
GO_0044314Biological processprotein K27-linked ubiquitination
GO_1900407Biological processregulation of cellular response to oxidative stress
GO_0043388Biological processpositive regulation of DNA binding
GO_0033132Biological processnegative regulation of glucokinase activity
GO_0043524Biological processnegative regulation of neuron apoptotic process
GO_0036503Biological processERAD pathway
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0000266Biological processmitochondrial fission
GO_0090141Biological processpositive regulation of mitochondrial fission
GO_1903214Biological processregulation of protein targeting to mitochondrion
GO_1900242Biological processregulation of synaptic vesicle endocytosis
GO_0010636Biological processpositive regulation of mitochondrial fusion
GO_0008344Biological processadult locomotory behavior
GO_0042053Biological processregulation of dopamine metabolic process
GO_1902803Biological processregulation of synaptic vesicle transport
GO_1905281Biological processpositive regulation of retrograde transport, endosome to Golgi
GO_0051583Biological processdopamine uptake involved in synaptic transmission
GO_0010906Biological processregulation of glucose metabolic process
GO_1903861Biological processpositive regulation of dendrite extension
GO_2000378Biological processnegative regulation of reactive oxygen species metabolic process
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0140251Biological processregulation protein catabolic process at presynapse
GO_0051881Biological processregulation of mitochondrial membrane potential
GO_0070050Biological processneuron cellular homeostasis
GO_1990000Biological processamyloid fibril formation
GO_0070936Biological processprotein K48-linked ubiquitination
GO_1905477Biological processpositive regulation of protein localization to membrane
GO_0043123Biological processpositive regulation of canonical NF-kappaB signal transduction
GO_1903542Biological processnegative regulation of exosomal secretion
GO_0032368Biological processregulation of lipid transport
GO_0070842Biological processaggresome assembly
GO_0097237Biological processcellular response to toxic substance
GO_1902530Biological processpositive regulation of protein linear polyubiquitination
GO_0035519Biological processprotein K29-linked ubiquitination
GO_0006513Biological processprotein monoubiquitination
GO_0032232Biological processnegative regulation of actin filament bundle assembly
GO_0051582Biological processpositive regulation of neurotransmitter uptake
GO_0031647Biological processregulation of protein stability
GO_0035249Biological processsynaptic transmission, glutamatergic
GO_0098793Cellular componentpresynapse
GO_0043005Cellular componentneuron projection
GO_0005634Cellular componentnucleus
GO_0098691Cellular componentdopaminergic synapse
GO_0099073Cellular componentmitochondrion-derived vesicle
GO_0097413Cellular componentLewy body
GO_0005739Cellular componentmitochondrion
GO_0005794Cellular componentGolgi apparatus
GO_0005783Cellular componentendoplasmic reticulum
GO_0014069Cellular componentpostsynaptic density
GO_0005737Cellular componentcytoplasm
GO_0005741Cellular componentmitochondrial outer membrane
GO_0019005Cellular componentSCF ubiquitin ligase complex
GO_0000151Cellular componentubiquitin ligase complex
GO_0048471Cellular componentperinuclear region of cytoplasm
GO_0016607Cellular componentnuclear speck
GO_0005829Cellular componentcytosol
GO_1990452Cellular componentParkin-FBXW7-Cul1 ubiquitin ligase complex
GO_0016235Cellular componentaggresome
GO_0042802Molecular functionidentical protein binding
GO_0031625Molecular functionubiquitin protein ligase binding
GO_0001664Molecular functionG protein-coupled receptor binding
GO_0008270Molecular functionzinc ion binding
GO_1990381Molecular functionubiquitin-specific protease binding
GO_0019900Molecular functionkinase binding
GO_1990444Molecular functionF-box domain binding
GO_0043274Molecular functionphospholipase binding
GO_0030544Molecular functionHsp70 protein binding
GO_0003779Molecular functionactin binding
GO_0043130Molecular functionubiquitin binding
GO_0017124Molecular functionSH3 domain binding
GO_0042826Molecular functionhistone deacetylase binding
GO_0061630Molecular functionubiquitin protein ligase activity
GO_0019899Molecular functionenzyme binding
GO_0031072Molecular functionheat shock protein binding
GO_0030165Molecular functionPDZ domain binding
GO_0051087Molecular functionprotein-folding chaperone binding
GO_0005515Molecular functionprotein binding
GO_0031624Molecular functionubiquitin conjugating enzyme binding
GO_0015631Molecular functiontubulin binding
GO_0044877Molecular functionprotein-containing complex binding
GO_0019901Molecular functionprotein kinase binding
GO_0003714Molecular functiontranscription corepressor activity
GO_0097602Molecular functioncullin family protein binding
GO_0008013Molecular functionbeta-catenin binding
GO_0004842Molecular functionubiquitin-protein transferase activity

IV. Literature review

[source]
Gene namePRKN
Protein nameParkinson protein 2 E3 ubiquitin protein ligase isoform 3
Parkin RBR E3 ubiquitin protein ligase (Truncated parkin variant SV4,8DEL) (Truncated parkin variant SV4DEL (EC 6.3.2.19))
E3 ubiquitin-protein ligase parkin (Parkin) (EC 2.3.2.31) (Parkin RBR E3 ubiquitin-protein ligase) (Parkinson juvenile disease protein 2) (Parkinson disease protein 2)
Parkin RBR E3 ubiquitin protein ligase (Truncated parkin variant SV3,8,9DEL (EC 6.3.2.19))
Parkinson disease (Autosomal recessive, juvenile) 2, parkin, isoform CRA_b (Parkinson protein 2 E3 ubiquitin protein ligase isoform 1)
RBR-type E3 ubiquitin transferase (EC 2.3.2.31)
E3 ubiquitin-protein ligase parkin (EC 2.3.2.31)
Parkin RBR E3 ubiquitin protein ligase (Parkinson protein 2 E3 ubiquitin protein ligase isoform 2)
PARK2 splice variant
Parkin
Truncated parkin variant SV1bINS (EC 6.3.2.19)
Parkin RBR E3 ubiquitin protein ligase
SynonymshCG_2029643
PARK2
DescriptionFUNCTION: Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins . Substrates include SYT11 and VDAC1 . Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 . Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context . Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation . Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation . Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy . Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components . Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy . Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin . After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis . When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 . Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy . The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 . This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes . Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma . Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A . Limits the production of reactive oxygen species (ROS) . Regulates cyclin-E during neuronal apoptosis . In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress . Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 . May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity . May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene . .

AccessionsENST00000647006.2
A0A1W5XGE1
D3K2X1
D3K2X2
A0A6I8PRS9
M4T2U2
ENST00000366892.5
A0A1W5XGE7
D3JZW5
A0A1W5XGD7
Q6S8G7
A0A669KBE3
Q6Q2I7
A0A0S2Z447
B1AKC3
O60260
X5DNX0
X5DR79
ENST00000366896.5 [O60260-6]
Q5XNR7
M4T4F2
Q6Q2I8
ENST00000673871.1
ENST00000674250.1
ENST00000366898.6 [O60260-1]
ENST00000338468.8
ENST00000479615.5 [O60260-3]
A0A6I8PII0
S4X465
ENST00000366897.5 [O60260-2]
Q5XNR8
A0A0S2Z446
ENST00000366894.6