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Appears in Networks 5

In-Edges 21

p(HGNC:PSMD4) association p(HGNC:PRKN) View Subject | View Object

Indeed, it has been reported that Parkin associates with the RPN10 (S5a) subunit of the 26S proteasome (Sakata et al., 2003) PubMed:14556719

a(GO:"actin filament") association p(HGNC:PRKN) View Subject | View Object

Parkin has been reported also to associate with actin filaments but not with microtubules (Huynh et al., 2000). PubMed:14556719

a(MESH:"Dopaminergic Neurons") negativeCorrelation p(HGNC:PRKN) View Subject | View Object

The overriding hypothesis is that a defect in Parkin will result in accumulation of this protein(s), which is toxic to the dopaminergic neurons PubMed:14556719

bp(MESH:"Synaptic Transmission") association p(HGNC:PRKN) View Subject | View Object

On the other hand, Parkin appears to have a role in synaptic transmission that has not been described previously and that was not possible to observe in patients. PubMed:14556719

complex(p(HGNC:PRKN), p(HGNC:STUB1)) increases act(p(HGNC:PRKN)) View Subject | View Object

Such a partner can be, for example, the cochaperone CHIP (Carboxy terminus of the Hsc70-Interacting Protein) that was found to increase the activity of Parkin, possibly by acting as an E4 (Imai et al., 2002) or the proteasome (see above). PubMed:14556719

p(HGNC:CCNE1) association p(HGNC:PRKN) View Subject | View Object

A rather surprising, recently discovered substrate of Parkin is cyclin E (Staropoli et al., 2003) that is ubiquitinated by the SCF complex that contains Parkin. PubMed:14556719

p(HGNC:GPR37) association p(HGNC:PRKN) View Subject | View Object

A second important substrate of Parkin is the Parkin-associated endothelial-like (Pael) receptor, a putative G protein-coupled transmembrane polypeptide (Imai et al., 2001). When overexpressed in cells, the receptor becomes misfolded PubMed:14556719

p(HGNC:PRKN, var("?")) decreases act(p(HGNC:PRKN)) View Subject | View Object

An interesting finding is that not all mutations found in Parkin in AR-JP patients are inactivatingmutations (see,for example, Chung et al., 2001; Corti et al., 2003; Imai et al., 2001 PubMed:14556719

p(HGNC:PRKN, var("?")) increases p(HGNC:PRKN) View Subject | View Object

The overriding hypothesis is that a defect in Parkin will result in accumulation of this protein(s), which is toxic to the dopaminergic neurons PubMed:14556719

p(HGNC:SNCA, pmod(Glyco)) association p(HGNC:PRKN) View Subject | View Object

The suggestion that the glycosylated form of alphaSYN is targeted by Parkin (Shimura et al., 2001) may resolve part of the enigma PubMed:14556719

p(HGNC:SNCA, pmod(OGlyco)) association p(HGNC:PRKN) View Subject | View Object

Another substrate of Parkin is a novel 22 kDa form of O-glycosylated SYN (Sp22) (Shimura et al., 2001) PubMed:14556719

p(INTERPRO:"IBR domain", var("?")) decreases act(p(HGNC:PRKN)) View Subject | View Object

Most of the point mutations described in Parkin reside in its RING-IBR-(In Between- RINGS)-RING domain and result in its inactivation (Lucking et al., 2000). PubMed:14556719

path(MESH:"Neurodegenerative Diseases") association p(HGNC:PRKN) View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:PRKN) View Subject | View Object

The E3 ligase Parkin, a protein implicated in Parkinson’s disease, creates an autophagy signal on mitochondria and also tags proteins elsewhere for proteasomal degradation (Yoshii et al. 2011). PubMed:22908190

Out-Edges 30

p(HGNC:PRKN) association p(HGNC:PSMD4) View Subject | View Object

Indeed, it has been reported that Parkin associates with the RPN10 (S5a) subunit of the 26S proteasome (Sakata et al., 2003) PubMed:14556719

p(HGNC:PRKN) association a(GO:"actin filament") View Subject | View Object

Parkin has been reported also to associate with actin filaments but not with microtubules (Huynh et al., 2000). PubMed:14556719

p(HGNC:PRKN) association bp(MESH:"Synaptic Transmission") View Subject | View Object

On the other hand, Parkin appears to have a role in synaptic transmission that has not been described previously and that was not possible to observe in patients. PubMed:14556719

p(HGNC:PRKN) negativeCorrelation a(MESH:"Dopaminergic Neurons") View Subject | View Object

The overriding hypothesis is that a defect in Parkin will result in accumulation of this protein(s), which is toxic to the dopaminergic neurons PubMed:14556719

p(HGNC:PRKN) increases p(HGNC:SEPT5, pmod(Ub)) View Subject | View Object

One of these substrates is Cell Division Control related protein (CDCrel-1) (Zhang et al., 2000), an ~44kDa member of the septin family of proteins that includes GTPases required for cytokinesis PubMed:14556719

p(HGNC:PRKN) association p(HGNC:GPR37) View Subject | View Object

A second important substrate of Parkin is the Parkin-associated endothelial-like (Pael) receptor, a putative G protein-coupled transmembrane polypeptide (Imai et al., 2001). When overexpressed in cells, the receptor becomes misfolded PubMed:14556719

p(HGNC:PRKN) decreases bp(GO:"response to unfolded protein") View Subject | View Object

Overexpression of Parkin can rescue cells from the UPR elicited by a variety of stresses, such as exposure to H2O2, DNA alkylating agents, short-wavelength UV light, high osmolarity, and heat shock (Imai et al., 2000) PubMed:14556719

p(HGNC:PRKN) decreases act(p(HGNC:SNCA)) View Subject | View Object

Of note is that overexpression of Parkin also suppresses alpha-synuclein (alphSYN) toxicity, suggesting that Parkin may play a role in regulating this protein as well (see below) PubMed:14556719

p(HGNC:PRKN) regulates p(HGNC:SNCA) View Subject | View Object

Of note is that overexpression of Parkin also suppresses alpha-synuclein (alphSYN) toxicity, suggesting that Parkin may play a role in regulating this protein as well (see below) PubMed:14556719

p(HGNC:PRKN) association p(HGNC:SNCA, pmod(OGlyco)) View Subject | View Object

Another substrate of Parkin is a novel 22 kDa form of O-glycosylated SYN (Sp22) (Shimura et al., 2001) PubMed:14556719

p(HGNC:PRKN) increases p(HGNC:SNCAIP, pmod(Ub)) View Subject | View Object

Parkin also ubiquitinates Synphilin-1, a protein of hitherto unknown function that contains a coiled-coiled domain and an ATP/GTP binding motif and that associates with alphaSYN (Chung et al., 2001). PubMed:14556719

p(HGNC:PRKN) increases p(HGNC:SNCAIP, pmod(Ub)) View Subject | View Object

Since inclusion bodies are lacking in most cases of AR-JP, it is possible that the ubiquitination of Synphilin by wildtype Parkin plays a role in their formation, by targeting ubiquitinated Synphilin to these bodies and removing it from the cytosol where it can be toxic PubMed:14556719

p(HGNC:PRKN) increases tloc(p(HGNC:SNCAIP, pmod(Ub)), fromLoc(GO:cytosol), toLoc(MESH:"Inclusion Bodies")) View Subject | View Object

Since inclusion bodies are lacking in most cases of AR-JP, it is possible that the ubiquitination of Synphilin by wildtype Parkin plays a role in their formation, by targeting ubiquitinated Synphilin to these bodies and removing it from the cytosol where it can be toxic PubMed:14556719

p(HGNC:PRKN) increases act(complex(GO:"proteasome complex")) View Subject | View Object

Concomitantly, it reduced the inhibition of the proteasome and the activation of caspase 12 that are induced by accumulation of the polyglutamine-containing fragment PubMed:14556719

p(HGNC:PRKN) decreases act(p(HGNC:CASP12)) View Subject | View Object

Concomitantly, it reduced the inhibition of the proteasome and the activation of caspase 12 that are induced by accumulation of the polyglutamine-containing fragment PubMed:14556719

p(HGNC:PRKN) association p(HGNC:CCNE1) View Subject | View Object

A rather surprising, recently discovered substrate of Parkin is cyclin E (Staropoli et al., 2003) that is ubiquitinated by the SCF complex that contains Parkin. PubMed:14556719

p(HGNC:PRKN) decreases p(HGNC:CCNE1) View Subject | View Object

Overexpression of Parkin is reported to attenuate cyclin E accumulation and rescue the cells from apoptosis PubMed:14556719

p(HGNC:PRKN) decreases bp(GO:"neuron apoptotic process") View Subject | View Object

Overexpression of Parkin is reported to attenuate cyclin E accumulation and rescue the cells from apoptosis PubMed:14556719

p(HGNC:PRKN) decreases bp(GO:"cell death") View Subject | View Object

In the dopamine-producing neuroblastoma cell line SH-SY5Y, Parkin rescued the cells from p38-induced cell death PubMed:14556719

p(HGNC:PRKN) increases p(HGNC:SYT11, pmod(Ub)) View Subject | View Object

Finally, Synaptotagmin XI has also recently been reported to be a substrate of Parkin (Huynh et al., 2003). It is possible that ubiquitination of this substrate affects synaptic vesicle transport and/or transmitter release. PubMed:14556719

p(HGNC:PRKN) regulates act(a(MESH:Actins)) View Subject | View Object

Yet, it is possible that the ligase regulates actin activity by ubiquitinating an actin-associated protein, which in turn affects the function of actin and thereby influences the movement of synaptic vesicles PubMed:14556719

p(HGNC:PRKN) association p(HGNC:SNCA, pmod(Glyco)) View Subject | View Object

The suggestion that the glycosylated form of alphaSYN is targeted by Parkin (Shimura et al., 2001) may resolve part of the enigma PubMed:14556719

p(HGNC:PRKN) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Several E3 Ub ligases, such as CHIP, Parkin, RNF182, may have roles in AD and other neurodegenerative diseases (Shimura et al., 2004; Khandelwal et al., 2011; Lei et al., 2012). PubMed:23528736

p(HGNC:PRKN) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

The E3 ligase Parkin, a protein implicated in Parkinson’s disease, creates an autophagy signal on mitochondria and also tags proteins elsewhere for proteasomal degradation (Yoshii et al. 2011). PubMed:22908190

p(HGNC:PRKN) increases bp(GO:mitophagy) View Subject | View Object

The E3 ligase Parkin, a protein implicated in Parkinson’s disease, creates an autophagy signal on mitochondria and also tags proteins elsewhere for proteasomal degradation (Yoshii et al. 2011). PubMed:22908190

p(HGNC:PRKN) increases bp(GO:"proteasomal protein catabolic process") View Subject | View Object

The E3 ligase Parkin, a protein implicated in Parkinson’s disease, creates an autophagy signal on mitochondria and also tags proteins elsewhere for proteasomal degradation (Yoshii et al. 2011). PubMed:22908190

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.