E3 ubiquitin-protein ligase parkin (Protein name
), PRKN2_HUMAN from NCBI database.
top
|
General Annotation
|
Antigen Annotation
|
3D
|
Predicted Eptitope
|
Vaild Sequence
|
Related Databases
|
Feedback
Gene name:
PARK2(PRKN);
Protein name:
E3 ubiquitin-protein ligase parkin;
Alternative:
Parkinson juvenile disease protein 2(Parkinson disease protein 2);
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6. Mediates 'Lys-63'-linked polyubiquitination by associating with UBE2V1. Part of a SCF-like complex, consisting of PARK2, CUL1 and FBXW7. Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11. Interacts and regulates the turnover of SEPT5. Part of a complex, including STUB1, HSP70 and GPR37. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PARK2 and GPR37, thus facilitating PARK2-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PARK2, whereas, STUB1 enhances the E3 activity of PARK2 through promotion of dissociation of HSP70 from PARK2-GPR37 complexes. Interacts with PSMD4 and PACRG. Interacts with LRRK2. Interacts with RANBP2. Interacts with SUMO1 but not SUMO2, which promotes nuclear localization and autoubiquitination. Interacts (via first RING-type domain) with AIMP2 (via N-terminus). Interacts with PSMA7 and RNF41. Interacts with PINK1.
Function:
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as '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 SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. 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. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene.
Subcellular Location:
Cytoplasm
cytosol
Nucleus
Endoplasmic reticulum
Mitochondrion
Mainly localizes in the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies. Relocates to dysfunctional mitochondria that have lost the mitochondial membrane potential; recruitement to mitochondria is PINK1-dependent.
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2);INVOLVEMENT IN PARK2
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [MRNA];SUBCELLULAR LOCATION;TISSUE SPECIFICITY;VARIANTS ARG-311 AND THR-371;IDENTIFICATION BY MASS SPECTROMETRY
3.
"Functional and molecular diversity of parkin." D'Agata V.
,
Scapagnini G.
,
Cavallaro S.
Submitted (2001-05) to the EMBL/GenBank/DDBJ databases
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4)
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 7 AND 8)
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION WITH UBE2L6 AND SEPT5;UBIQUITINATION OF SEPT5
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION;UBIQUITINATION OF SNCAIP;CHARACTERIZATION OF VARIANTS PARK2 ARG-240; CYS-256; TRP-275 AND ASN-415;MUTAGENESIS OF CYS-337; CYS-421 AND CYS-431
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: UBIQUITINATION OF AN O-GLYCOSYLATED ISOFORM OF SNCAIP;SUBCELLULAR LOCATION;CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION WITH STUB1 AND HSP70;UBIQUITINATION OF STUB1
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION WITH SYT11;CHARACTERIZATION OF VARIANTS PARK2 GLY-289 AND ARG-418
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;INTERACTION WITH FBXW7 AND CUL1;UBIQUITINATION OF CYCLIN E
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY;SUBCELLULAR LOCATION
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION WITH RNF41;UBIQUITINATION;MUTAGENESIS OF CYS-421;FUNCTION
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN PROTECTION OF APOPTOSIS;CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441;DOMAIN
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;INTERACTION WITH BCL2;SUBCELLULAR LOCATION;CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY;SUBCELLULAR LOCATION;INTERACTION WITH PINK1;CHARACTERIZATION OF VARIANTS PARK ASN-415 AND ASP-430
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;INTERACTION WITH ZNF746;CHARACTERIZATION OF VARIANTS PARK2 TRP-275; ASP-430 AND PHE-431
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;REACTION MECHANISM;INTERACTION WITH UBE2L3
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;INTERACTION WITH CHPF;SUBCELLULAR LOCATION
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: PHOSPHORYLATION AT SER-65;FUNCTION;SUBCELLULAR LOCATION
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;SUBCELLULAR LOCATION;INTERACTION WITH FBXO7
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: INTERACTION WITH BAG4; BAG5; HSPA1L; HSPA1A AND HSPA8
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN MITOPHAGY;INTERACTION WITH MFN2;SUBCELLULAR LOCATION
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;PHOSPHORYLATION AT SER-65;UBIQUITIN-BINDING;ENZYME REGULATION;MUTAGENESIS OF SER-65
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION;PHOSPHORYLATION AT SER-65;UBIQUITIN-BINDING;ENZYME REGULATION;MUTAGENESIS OF SER-65 AND TRP-403
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: STRUCTURE BY NMR OF 1-76;INTERACTION WITH PSMD4
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: STRUCTURE BY NMR OF 307-384 IN COMPLEX WITH ZINC IONS;CHARACTERIZATION OF VARIANT PARK2 PRO-351;MUTAGENESIS OF CYS-332 AND CYS-365;IDENTIFICATION BY MASS SPECTROMETRY
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 137-465;ENZYME REGULATION;MUTAGENESIS OF CYS-431; HIS-433 AND GLU-444
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 137-465;ACTIVE SITE;ENZYME REGULATION;MUTAGENESIS OF CYS-431; HIS-433 AND GLU-444
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 ASN-161; CYS-256; TRP-275 AND ASN-415;VARIANTS ASN-167; LEU-380 AND ASN-394
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 ASN-161; ASN-211; CYS-256; TRP-275; ASN-280; GLY-289; GLU-328; CYS-334; ASN-415 AND ASP-430
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 GLU-82; CYS-256; TRP-275; GLU-328 AND ARG-441
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 ASN-211; TRP-275; ASP-430 AND LEU-437
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANT PARK2 MET-15;VARIANTS LEU-380 AND ASN-394
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 PRO-42; LEU-192; CYS-256; TRP-275; ASP-430 AND LEU-437
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 GLN-33; GLU-82; ASP-430 AND LEU-437;VARIANTS PARK TYR-253; CYS-256; TRP-275 AND ASN-280;VARIANTS LEU-380 AND ASN-394
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 VAL-192; ASN-211; MET-240 AND LEU-437;VARIANT ASN-167;INVOLVEMENT IN LATE-ONSET PARK
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: VARIANTS PARK2 PRO-42; CYS-402; ASN-415 AND ARG-418
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ASN-211; ARG-240; ASN-280 AND GLU-328