| + |
PRKN | down-regulates quantity by destabilization 
ubiquitination
|
PHGDH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269075 |
Lys330 |
SAFSPHTkPWIGLAE |
Homo sapiens |
A-549 Cell, Hs-578T Cell |
| pmid |
sentence |
| 32478681 |
Parkin binds to PHGDH and degrades it through ubiquitination to inhibit serine synthesis, which contributes greatly to the tumor-suppressive function of Parkin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MTOR | down-regulates activity
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277586 |
Ser127 |
AVILHTDsRKDSPPA |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 35191952 |
MTOR phosphorylates PARK2 at Ser127 Through biochemical, mutational, and genetic studies, we identified PARK2 as a mTORC1 substrate. mTORC1 phosphorylates PARK2 at Ser127, which blocks its cellular ubiquitination activity, thereby hindering its tumor suppressor effect on eIF4B's stability. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
CDK5 | down-regulates
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153445 |
Ser131 |
HTDSRKDsPPAGSPA |
Homo sapiens |
|
| pmid |
sentence |
| 17327227 |
Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
PLK1 | up-regulates activity 
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276938 |
Ser378 |
AYHEGECsAVFEASG |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26387737 |
Parkin Is Phosphorylated by Plk1 at Ser378 and Activated during Mitosis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PINK1 | up-regulates activity
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270345 |
Ser65 |
NCDLDQQsIVHIVQR |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22724072 |
PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
PINK1 | up-regulates
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-197976 |
Ser65 |
NCDLDQQsIVHIVQR |
Homo sapiens |
|
| pmid |
sentence |
| 22724072 |
We show that human pink1 is specifically activated by mitochondrial membrane potential (??m) depolarization, enabling it to phosphorylate parkin at ser(65). We further show that phosphorylation of parkin at ser(65) leads to marked activation of its e3 ligase activity that is prevented by mutation of ser(65) or inactivation of pink1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
ABL1 | down-regulates
phosphorylation
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167853 |
Tyr143 |
SPAGRSIyNSFYVYC |
Homo sapiens |
|
| pmid |
sentence |
| 20823226 |
Here we show that the nonreceptor tyrosine kinase c-abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin e3 ligase activity and protective function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
PRKN | down-regulates quantity by destabilization
polyubiquitination
|
PSMD4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272749 |
|
|
in vitro |
|
| pmid |
sentence |
| 19240029 |
S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination, polyubiquitination
|
ZNF746 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273726 |
|
|
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 28122242 |
PINK1 is required for Parkin ubiquitination and degradation of PARIS. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272758 |
|
|
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 21376232 |
. Parkin ubiquitinates and regulates the ubiquitin proteasomal degradation of PARIS |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
BAG5 | down-regulates activity
binding
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261198 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15603737 |
Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity Immunoprecipitation (IP) of GFP-parkin resulted in the coimmunoprecipitation of both Hsp70 and BAG5 or BAG5(DARA) (Figure 4A). Furthermore, IP of GFP-parkin resulted in the coimmunoprecipitation of BAG5 or BAG5 (DARA) in the absence of overexpressed Hsp70. Taken together, these data demonstrate that BAG5 can directly inhibit parkin-mediated autoubiquitinylation independently of Hsp70. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | down-regulates quantity by destabilization
polyubiquitination
|
SYT11 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272672 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12925569 |
Parkin binds to the C2A and C2B domains of synaptotagmin XI resulting in the polyubiquitination of synaptotagmin XI. Parkin-mediated ubiquitination also enhances the turnover of sytXI. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ubiquitin | up-regulates activity
binding
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270343 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 24784582 |
The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
UBC | up-regulates activity
binding
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249692 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 26161729 |
Mechanism of phospho-ubiquitin-induced PARKIN activation|PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN|Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
PRKN | down-regulates quantity by destabilization
polyubiquitination
|
RHOT2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272726 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22078885 |
PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STUB1 | up-regulates activity
binding
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272888 |
|
|
in vitro |
|
| pmid |
sentence |
| 12150907 |
In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination
|
SNCA |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249705 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 12666095 |
Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination
|
HIF3A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263089 |
|
|
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 27551449 |
Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | up-regulates
ubiquitination
|
EPS15 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148218 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 16862145 |
Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
UBA52 | up-regulates activity
binding
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270344 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 24784582 |
The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination
|
HSD17B10 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272823 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 25591737 |
This study identifies the multifunctional PD-related mitochondrial matrix enzyme 17-β hydroxysteroid dehydrogenase type 10 (HSD17B10) as a new Parkin substrate. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
PRKN | down-regulates quantity
ubiquitination
|
MFN1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272779 |
|
|
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 20871098 |
Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UBE2L3 | up-regulates activity
ubiquitination
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272734 |
|
|
in vitro |
|
| pmid |
sentence |
| 19240029 |
Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKN | down-regulates activity
ubiquitination
|
EPS15 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-243282 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 16862145 |
Treatment of cells with EGF stimulates parkin binding to both Eps15 and the EGFR and promotes parkin-mediated ubiquitination of Eps15. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PRKN | up-regulates quantity by stabilization
ubiquitination
|
SNCAIP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272595 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11590439 |
Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1. Co-expression of alpha-synuclein, synphilin-1 and parkin result in the formation of Lewy-body-like ubiquitin-positive cytosolic inclusions. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | down-regulates quantity by destabilization
polyubiquitination
|
SEPTIN5 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272673 |
|
|
in vitro |
|
| pmid |
sentence |
| 14559152 |
SEPT5_v2 is highly homologous to another septin, SEPT5, which was recently identified as a target for parkin-mediated ubiquitination. SEPT5_v2 binds to parkin at the amino terminus and in the ring finger domains.Parkin ubiquitinates SEPT5_v2 in vitro, and both SEPT5_v1 and SEPT5_v2 accumulate in brains of patients with ARJP, suggesting that parkin is essential for the normal metabolism of these proteins. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination
|
GPR37 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249706 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12666095 |
Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | down-regulates quantity
ubiquitination
|
MFN2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272780 |
|
|
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 20871098 |
Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | down-regulates quantity by destabilization
ubiquitination
|
RANBP2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259116 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16332688 |
Our findings suggested that the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways. Furthermore, Parkin controls the intracellular levels of sumoylated HDAC4, as a result of the ubiquitination and degradation of RanBP2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RNF41 | down-regulates quantity by destabilization
polyubiquitination
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272639 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18541373 |
Here we further demonstrated that overexpression of Nrdp1 significantly reduced the endogenous Parkin level in an Nrdp1 dosage-dependent and proteasome-dependent manner. More importantly, Nrdp1 ubiquitinated Parkin and catalyzed the poly-ubiquitin chains on Parkin in vitro as well as in cells, indicating Parkin is an Nrdp1 substrate. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
PRKN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271041 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKN | down-regulates quantity by destabilization
polyubiquitination
|
PACRG |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272889 |
|
|
in vitro |
|
| pmid |
sentence |
| 12150907 |
In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). |
|
| Publications: |
1 |
Organism: |
In Vitro |
3.0
PRKN
- 
- 