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Protein Page:
PARK2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
PARK2 a component of 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. 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. 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. Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Found in serum. Belongs to the RBR family. Parkin subfamily. 6 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Ubiquitin conjugating system; EC 6.3.2.19; Ubiquitin ligase; Ligase; EC 6.3.2.-
Cellular Component: Golgi apparatus; mitochondrion; perinuclear region of cytoplasm; endoplasmic reticulum; cytoplasm; nucleus; cytosol; ubiquitin ligase complex
Molecular Function: identical protein binding; ubiquitin binding; protein binding; zinc ion binding; chaperone binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; protein kinase binding; kinase binding; ligase activity; PDZ domain binding
Biological Process: ubiquitin-dependent protein catabolic process; protein monoubiquitination; cell death; proteasomal ubiquitin-dependent protein catabolic process; negative regulation of actin filament bundle formation; protein autoubiquitination; positive regulation of I-kappaB kinase/NF-kappaB cascade; protein polyubiquitination; central nervous system development; transcription, DNA-dependent; protein ubiquitination during ubiquitin-dependent protein catabolic process; protein ubiquitination; negative regulation of insulin secretion; negative regulation of glucokinase activity; negative regulation of protein amino acid phosphorylation; regulation of transcription, DNA-dependent; cellular protein catabolic process; mitochondrion degradation; regulation of autophagy; negative regulation of neuron apoptosis
Reference #:  O60260 (UniProtKB)
Alt. Names/Synonyms: AR-JP; E3 ubiquitin-protein ligase parkin; LPRS2; PARK2; parkin; parkin 2; Parkinson disease (autosomal recessive, juvenile) 2, parkin; Parkinson disease protein 2; Parkinson juvenile disease protein 2; PDJ; PRKN; PRKN2
Gene Symbols: PARK2
Molecular weight: 51,641 Da
Basal Isoelectric point: 6.71  Predict pI for various phosphorylation states
CST Pathways:  Parkinson's Disease
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

PARK2

Protein Structure Not Found.


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Sites Implicated In
enzymatic activity, induced: S65‑p
enzymatic activity, inhibited: S131‑p, Y143‑p
ubiquitination: Y143‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 S9-p IVFVRFNsSHGFPVE
0 1 S19-p GFPVEVDsDTSIFQL
1 0 K27-ub DTSIFQLkEVVAKRQ
1 0 K48-ub LRVIFAGkELRNDWT
10 1 S65-p NCDLDQQsIVHIVQR
1 0 K76-ub IVQRPWRkGQEMNAT
0 1 G77 VQRPWRkGQEMNATG
0 1 M80 PWRkGQEMNATGGDD
1 0 S101-p GCEREPQsLTRVDLs
0 2 S108-p sLTRVDLsSSVLPGD
0 1 S116-p SSVLPGDsVGLAVIL
3 1 S131-p HTDSRKDsPPAGsPA
1 1 S136-p KDsPPAGsPAGRSIy
1 0 Y143-p sPAGRSIyNSFYVYC
0 1 S193-p VLIPNRMsGECQsPH
0 1 S198-p RMsGECQsPHCPGtS
0 1 T204-p QsPHCPGtSAEFFFK
1 0 S296-p CVAGCPNsLIKELHH
0 2 Y372-p CRECKEAyHEGECsA
1 1 S378-p AyHEGECsAVFEASG
0 2 T388-p FEASGTTtQAyRVDE
0 1 Y391-p SGTTtQAyRVDERAA
  mouse

 
S9 IVFVRFNSSYGFPVE
S19 GFPVEVDSDTSILQL
- under review  
- under review  
S65 NCDLEQQSIVHIVQR
- under review  
S77-p VQRPRRRsHEtNASG
T80-p PRRRsHEtNASGGDE
S101 GSIWESRSLTRVDLs
S108-p SLTRVDLsSHTLPVD
S116 SHTLPVDSVGLAVIL
S131 DTDSKRDSEAARGPV
G136 RDSEAARGPVKPTYN
Y142 RGPVKPTYNSFFIYC
S192 VLIPNRMSGECQSPD
S197 RMSGECQSPDCPGTR
T203 QSPDCPGTRAEFFFK
S295 CVAGCPNSLIKELHH
Y371 CRDCKEAYHEGDCDS
D377 AYHEGDCDSLLEPSG
S387 LEPSGATSQAYRVDK
Y390 SGATSQAYRVDKRAA
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