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p(HGNC:PRKN)

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Entity

Name
PRKN
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 5

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Alpha-synuclein oligomers: a new hope v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

complex(GO:"SCF ubiquitin ligase complex") hasComponent p(HGNC:PRKN) View Subject | View Object

Appears in Networks:

complex(a(GO:"proteasome complex"), p(HGNC:PRKN)) hasComponent p(HGNC:PRKN) View Subject | View Object

Appears in Networks:

complex(p(HGNC:ATXN3, frag("?")), p(HGNC:PRKN)) hasComponent p(HGNC:PRKN) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

composite(a(PUBCHEM:164810), p(HGNC:PRKN)) hasComponent p(HGNC:PRKN) View Subject | View Object

Appears in Networks:

composite(p(HGNC:PRKN), p(HGNC:UBE2G1), p(HGNC:UBE2J1)) hasComponent p(HGNC:PRKN) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:
Annotations
MeSH
Parkinsonian Disorders

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

An important player in the pathogenesis of PD is Parkin (PARK2)) PubMed:14556719

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:PRKN) hasVariant p(HGNC:PRKN, var("p.Arg42")) View Subject | View Object

Appears in Networks:

p(HGNC:PRKN) hasVariant p(HGNC:PRKN, var("p.Lys161Asn")) View Subject | View Object

Appears in Networks:

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

An important player in the pathogenesis of PD is Parkin (PARK2)) PubMed:14556719

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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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.