CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000895
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase parkin 
Protein Synonyms/Alias
 Parkinson juvenile disease protein 2; Parkinson disease protein 2 
Gene Name
 PARK2 
Gene Synonyms/Alias
 PRKN 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
408ARWEAASKETIKKTTubiquitination[1]
412AASKETIKKTTKPCPubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 1 76 Ubiquitin-like.
 ZN_FING 238 293 RING-type 1; atypical.
 ZN_FING 313 377 IBR-type.
 ZN_FING 418 449 RING-type 2.
 REGION 204 238 SYT11 binding 1.
 REGION 257 293 SYT11 binding 2.  
Keyword
 3D-structure; Alternative splicing; Autophagy; Complete proteome; Cytoplasm; Disease mutation; Endoplasmic reticulum; Ligase; Metal-binding; Mitochondrion; Neurodegeneration; Nucleus; Parkinson disease; Parkinsonism; Polymorphism; Reference proteome; Repeat; S-nitrosylation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 465 AA 
Protein Sequence
MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD 60
LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA 120
VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQGP 180
SCWDDVLIPN RMSGECQSPH CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT 240
CTDVRSPVLV FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE 300
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV TCEGGNGLGC 360
GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ ARWEAASKET IKKTTKPCPR 420
CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG CEWNRVCMGD HWFDV 465 
Gene Ontology
 GO:0016235; C:aggresome; IDA:BHF-UCL.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; IDA:UniProtKB.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0070842; P:aggresome assembly; IMP:BHF-UCL.
 GO:0007417; P:central nervous system development; TAS:ProtInc.
 GO:0000422; P:mitochondrion degradation; IMP:UniProtKB.
 GO:0032232; P:negative regulation of actin filament bundle assembly; IDA:BHF-UCL.
 GO:0043524; P:negative regulation of neuron apoptotic process; IDA:BHF-UCL.
 GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL.
 GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:BHF-UCL.
 GO:0070997; P:neuron death; IDA:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:BHF-UCL.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
 GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
 GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB. 
Interpro
 IPR003977; Parkin.
 IPR000626; Ubiquitin.
 IPR019955; Ubiquitin_supergroup.
 IPR002867; Znf_C6HC. 
Pfam
 PF01485; IBR
 PF00240; ubiquitin 
SMART
 SM00647; IBR
 SM00213; UBQ 
PROSITE
 PS00299; UBIQUITIN_1
 PS50053; UBIQUITIN_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS
 PR01475; PARKIN.