Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase parkin

Gene

PRKN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951). 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 (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed:25621951). Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death (PubMed:21376232). Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.28 Publications

Miscellaneous

The parkin locus (PRKN), adjacent to the 6q telomere is hyper-recombinable and lies within FRA6E, the third most common fragile site in tumor tissue.

Catalytic activityi

[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine.1 Publication

Activity regulationi

In the autoinhibited state the side chain of Phe-463 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-431, whereas the REP repressor element binds RING-1 and blocks its E2-binding site (PubMed:23727886, PubMed:23770887). Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-431 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form (PubMed:24660806, PubMed:24784582, PubMed:25527291). According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression (PubMed:24751536).6 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi238Zinc 1PROSITE-ProRule annotation1
Metal bindingi241Zinc 1PROSITE-ProRule annotation1
Metal bindingi253Zinc 2PROSITE-ProRule annotation1
Metal bindingi257Zinc 2; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi260Zinc 1PROSITE-ProRule annotation1
Metal bindingi263Zinc 1PROSITE-ProRule annotation1
Metal bindingi289Zinc 2PROSITE-ProRule annotation1
Metal bindingi293Zinc 2PROSITE-ProRule annotation1
Metal bindingi332Zinc 3PROSITE-ProRule annotation1
Metal bindingi337Zinc 3PROSITE-ProRule annotation1
Metal bindingi352Zinc 3PROSITE-ProRule annotation1
Metal bindingi360Zinc 3PROSITE-ProRule annotation1
Metal bindingi365Zinc 4PROSITE-ProRule annotation1
Metal bindingi368Zinc 4PROSITE-ProRule annotation1
Metal bindingi373Zinc 4; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi377Zinc 4PROSITE-ProRule annotation1
Metal bindingi418Zinc 5PROSITE-ProRule annotation1
Metal bindingi421Zinc 5PROSITE-ProRule annotation1
Active sitei431PROSITE-ProRule annotation1
Metal bindingi436Zinc 5PROSITE-ProRule annotation1
Metal bindingi441Zinc 5PROSITE-ProRule annotation1
Metal bindingi446Zinc 6PROSITE-ProRule annotation1
Metal bindingi449Zinc 6PROSITE-ProRule annotation1
Metal bindingi457Zinc 6PROSITE-ProRule annotation1
Metal bindingi461Zinc 6; via tele nitrogenPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri141 – 225RING-type 0; atypicalAdd BLAST85
Zinc fingeri238 – 293RING-type 1PROSITE-ProRule annotationAdd BLAST56
Zinc fingeri313 – 377IBR-typePROSITE-ProRule annotationAdd BLAST65
Zinc fingeri418 – 449RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST32

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAutophagy, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-5205685 Pink/Parkin Mediated Mitophagy
R-HSA-5689877 Josephin domain DUBs
R-HSA-977225 Amyloid fiber formation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiO60260
SIGNORiO60260
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase parkinCurated (EC:2.3.2.311 Publication)
Short name:
Parkin
Alternative name(s):
Parkin RBR E3 ubiquitin-protein ligaseImported
Parkinson juvenile disease protein 2
Short name:
Parkinson disease protein 2
Gene namesi
Name:PRKNImported
Synonyms:PARK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000185345.18
HGNCiHGNC:8607 PRKN
MIMi602544 gene
neXtProtiNX_O60260

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Parkinson disease (PARK)3 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996 and PubMed:12629236).
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
See also OMIM:168600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019749253C → Y in PARK; late onset. 1 PublicationCorresponds to variant dbSNP:rs747427602Ensembl.1
Natural variantiVAR_019753280D → N in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 PublicationsCorresponds to variant dbSNP:rs72480422Ensembl.1
Parkinson disease 2 (PARK2)30 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent.
See also OMIM:600116
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01973315V → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs532703934Ensembl.1
Natural variantiVAR_01973433R → Q in PARK2. 1 PublicationCorresponds to variant dbSNP:rs147757966Ensembl.1
Natural variantiVAR_01973537P → L in PARK2. 1 PublicationCorresponds to variant dbSNP:rs148990138Ensembl.1
Natural variantiVAR_01973642R → P in PARK2; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding; decreases ubiquitination and degradation; increased aggregation. 6 PublicationsCorresponds to variant dbSNP:rs368134308Ensembl.1
Natural variantiVAR_01973746A → P in PARK2. 1 Publication1
Natural variantiVAR_07007856V → E in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853059EnsemblClinVar.1
Natural variantiVAR_01973882A → E in PARK2. 3 PublicationsCorresponds to variant dbSNP:rs55774500EnsemblClinVar.1
Natural variantiVAR_01973992A → V in PARK2. Corresponds to variant dbSNP:rs566229879Ensembl.1
Natural variantiVAR_019741161K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 5 PublicationsCorresponds to variant dbSNP:rs137853057EnsemblClinVar.1
Natural variantiVAR_054107192M → L in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019743192M → V in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019744211K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2. 5 PublicationsCorresponds to variant dbSNP:rs137853060EnsemblClinVar.1
Natural variantiVAR_019746212C → Y in PARK2. 2 PublicationsCorresponds to variant dbSNP:rs137853058EnsemblClinVar.1
Natural variantiVAR_019747240T → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019748240T → R in PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization. 6 PublicationsCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019754284G → R in PARK2. Corresponds to variant dbSNP:rs751037529EnsemblClinVar.1
Natural variantiVAR_019755289C → G in PARK2; increased aggregation; fails to ubiquitinate SYT11; loses ability to bind SYT11; impaired relocalization to damaged mitochondria; loss of function in mitophagy. 3 PublicationsCorresponds to variant dbSNP:rs55961220Ensembl.1
Natural variantiVAR_019756328G → E in PARK2; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 Publications1
Natural variantiVAR_019759351T → P in PARK2; impairs folding of IBR domain. 2 Publications1
Natural variantiVAR_070079402R → C in PARK2. 1 PublicationCorresponds to variant dbSNP:rs55830907EnsemblClinVar.1
Natural variantiVAR_019763415T → N in PARK2; impairs the ability to ubiquitinate SNCAIP; does not affect turnover of CDCRE1; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria. 5 PublicationsCorresponds to variant dbSNP:rs778125254Ensembl.1
Natural variantiVAR_070080418C → R in PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression; fails to ubiquitinate SYT11 but does not loose ability to bind SYT11. 3 Publications1
Natural variantiVAR_019764430G → D in PARK2; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria; impaired E3 ubiquitin-protein ligase toward ZNF746. 7 PublicationsCorresponds to variant dbSNP:rs191486604EnsemblClinVar.1
Natural variantiVAR_019765431C → F in PARK2; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2. 3 PublicationsCorresponds to variant dbSNP:rs397514694EnsemblClinVar.1
Natural variantiVAR_019766437P → L in PARK2; impaired E3 ubiquitin-protein ligase toward BCL2. 5 PublicationsCorresponds to variant dbSNP:rs149953814EnsemblClinVar.1
Natural variantiVAR_019767441C → R in PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 2 PublicationsCorresponds to variant dbSNP:rs778305273Ensembl.1
Defects in PRKN may be involved in the development and/or progression of ovarian cancer.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65S → E: Phosphomimetic mutant; still requires PINK1 for activation. PRKN is activated in presence of phosphorylated ubiquitin. 2 Publications1
Mutagenesisi332C → S: Impairs folding of IBR domain. 1 Publication1
Mutagenesisi337C → A: Impairs the ability to ubiquitinate SNCAIP. 1 Publication1
Mutagenesisi365C → S: Impairs protein folding. 1 Publication1
Mutagenesisi403W → A: Decreased autoinhibition and increased E3 activity. 1 Publication1
Mutagenesisi421C → A: Impairs the ability of self-ubiquitination and to ubiquitinate SNCAIP. 2 Publications1
Mutagenesisi431C → S: Impairs the ability to ubiquitinate target proteins. 3 Publications1
Mutagenesisi433H → N or A: Impaired activity. 2 Publications1
Mutagenesisi444E → Q or A: Impaired activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi5071
GeneReviewsiPARK2
MalaCardsiPRKN
MIMi168600 phenotype
600116 phenotype
OpenTargetsiENSG00000185345
Orphaneti2828 Young-onset Parkinson disease
PharmGKBiPA32942

Polymorphism and mutation databases

BioMutaiPARK2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000585761 – 465E3 ubiquitin-protein ligase parkinAdd BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei65Phosphoserine; by PINK13 Publications1

Post-translational modificationi

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation (PubMed:19229105). Also polyubiquitinated by RNF41 for proteasomal degradation.1 Publication
S-nitrosylated. The inhibition of PRKN ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PRKN substrates.1 Publication
Phosphorylation at Ser-65 by PINK1 contributes to activate PRKN activity. It is however not sufficient and requires binding to phosphorylated ubiquitin as well.3 Publications

Keywords - PTMi

Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiO60260
PeptideAtlasiO60260
PRIDEiO60260
ProteomicsDBi49290
49291 [O60260-2]
49292 [O60260-3]
49293 [O60260-4]
49294 [O60260-5]
49295 [O60260-6]

PTM databases

iPTMnetiO60260
PhosphoSitePlusiO60260

Expressioni

Tissue specificityi

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 (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000185345 Expressed in 111 organ(s), highest expression level in frontal cortex
CleanExiHS_PARK2
ExpressionAtlasiO60260 baseline and differential
GenevisibleiO60260 HS

Organism-specific databases

HPAiCAB016257
HPA036012

Interactioni

Subunit structurei

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 PRKN, 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 PRKN and GPR37, thus facilitating PRKN-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PRKN, whereas, STUB1 enhances the E3 activity of PRKN through promotion of dissociation of HSP70 from PRKN-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. Interacts with CHPF, the interaction with isoform 2 may facilitate PRKN transport into the mitochondria. Interacts with MFN2 (phosphorylated), promotes PRKN localization in dysfunctional depolarized mitochondria. Interacts with FBXO7; this promotes translocation to dysfunctional depolarized mitochondria. Interacts with heat shock protein 70 family members, including HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes translocation to damaged mitochondria. Interacts with BAG4 and, to a lesser extent, BAG5; interaction with BAG4 inhibits translocation to damaged mitochondria. Forms a complex with PINK1 and PARK7 (PubMed:19229105).25 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111105, 456 interactors
CORUMiO60260
DIPiDIP-37655N
IntActiO60260, 37 interactors
MINTiO60260
STRINGi9606.ENSP00000355865

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60260
SMRiO60260
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60260

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 76Ubiquitin-likePROSITE-ProRule annotationAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni204 – 238SYT11 binding 11 PublicationAdd BLAST35
Regioni234 – 465TRIAD supradomainPROSITE-ProRule annotationAdd BLAST232
Regioni257 – 293SYT11 binding 21 PublicationAdd BLAST37
Regioni378 – 410REPBy similarityAdd BLAST33

Domaini

The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.1 Publication
The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.1 Publication
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (PubMed:21532592).1 Publication

Sequence similaritiesi

Belongs to the RBR family. Parkin subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri141 – 225RING-type 0; atypicalAdd BLAST85
Zinc fingeri238 – 293RING-type 1PROSITE-ProRule annotationAdd BLAST56
Zinc fingeri313 – 377IBR-typePROSITE-ProRule annotationAdd BLAST65
Zinc fingeri418 – 449RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST32

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0006 Eukaryota
ENOG410YG4B LUCA
GeneTreeiENSGT00390000011034
HOGENOMiHOG000013184
HOVERGENiHBG053682
InParanoidiO60260
KOiK04556
OMAiCGYVFCR
OrthoDBiEOG091G09PU
PhylomeDBiO60260
TreeFamiTF314529

Family and domain databases

InterProiView protein in InterPro
IPR031127 E3_UB_ligase_RBR
IPR002867 IBR_dom
IPR003977 Parkin
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR11685 PTHR11685, 1 hit
PfamiView protein in Pfam
PF01485 IBR, 2 hits
PF00240 ubiquitin, 1 hit
PIRSFiPIRSF037880 Parkin, 1 hit
PRINTSiPR01475 PARKIN
SMARTiView protein in SMART
SM00647 IBR, 2 hits
SM00213 UBQ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS51873 TRIAD, 1 hit
PS50053 UBIQUITIN_2, 1 hit

Sequences (8+)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 8 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60260-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL
60 70 80 90 100
RNDWTVQNCD LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ
110 120 130 140 150
SLTRVDLSSS VLPGDSVGLA VILHTDSRKD SPPAGSPAGR SIYNSFYVYC
160 170 180 190 200
KGPCQRVQPG KLRVQCSTCR QATLTLTQGP SCWDDVLIPN RMSGECQSPH
210 220 230 240 250
CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT CTDVRSPVLV
260 270 280 290 300
FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE
310 320 330 340 350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV
360 370 380 390 400
TCEGGNGLGC GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ
410 420 430 440 450
ARWEAASKET IKKTTKPCPR CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG
460
CEWNRVCMGD HWFDV
Length:465
Mass (Da):51,641
Last modified:October 17, 2006 - v2
Checksum:i9A8BB802A3FC84C3
GO
Isoform 2 (identifier: O60260-2) [UniParc]FASTAAdd to basket
Also known as: SV5DEL

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.

Show »
Length:437
Mass (Da):48,713
Checksum:iA435AF6495DED559
GO
Isoform 3 (identifier: O60260-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     291-297: AGCPNSL → VCLLPGM
     298-465: Missing.

Show »
Length:218
Mass (Da):23,639
Checksum:i4CB1B7EBD8A25F4B
GO
Isoform 4 (identifier: O60260-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.

Show »
Length:274
Mass (Da):30,616
Checksum:iCAE5D2F530395FA1
GO
Isoform 5 (identifier: O60260-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     290-290: V → VGTGDTVVLRGALGGFRRGV
     362-368: FAFCREC → YGQRRTK
     369-465: Missing.

Show »
Length:387
Mass (Da):42,407
Checksum:i48C0F41C86226606
GO
Isoform 6 (identifier: O60260-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-206: Missing.

Show »
Length:316
Mass (Da):35,631
Checksum:i4AE7F62C46499A24
GO
Isoform 7 (identifier: O60260-7) [UniParc]FASTAAdd to basket
Also known as: SV5,9DEL

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.
     312-361: Missing.

Show »
Length:387
Mass (Da):43,485
Checksum:i0521F623B06DDDE6
GO
Isoform 8 (identifier: O60260-8) [UniParc]FASTAAdd to basket
Also known as: SV9DEL

The sequence of this isoform differs from the canonical sequence as follows:
     312-361: Missing.

Show »
Length:415
Mass (Da):46,413
Checksum:i0EF24F73366A6454
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X0Z9A0A087X0Z9_HUMAN
RBR-type E3 ubiquitin transferase
PRKN
176Annotation score:
A0A087WX46A0A087WX46_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
74Annotation score:
B1AKC3B1AKC3_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN PARK2
368Annotation score:
A0A087WU39A0A087WU39_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
201Annotation score:
A0A087X1E2A0A087X1E2_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
87Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti223S → P in BAA25751 (PubMed:9560156).Curated1
Sequence conflicti223S → P in AAM21458 (Ref. 3) Curated1
Sequence conflicti223S → P in AAM21457 (Ref. 3) Curated1
Sequence conflicti289 – 290CV → MI in AAM21461 (PubMed:19501131).Curated2
Sequence conflicti339A → V in AAS88422 (Ref. 9) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01973315V → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs532703934Ensembl.1
Natural variantiVAR_01973433R → Q in PARK2. 1 PublicationCorresponds to variant dbSNP:rs147757966Ensembl.1
Natural variantiVAR_01973537P → L in PARK2. 1 PublicationCorresponds to variant dbSNP:rs148990138Ensembl.1
Natural variantiVAR_01973642R → P in PARK2; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding; decreases ubiquitination and degradation; increased aggregation. 6 PublicationsCorresponds to variant dbSNP:rs368134308Ensembl.1
Natural variantiVAR_01973746A → P in PARK2. 1 Publication1
Natural variantiVAR_07007856V → E in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853059EnsemblClinVar.1
Natural variantiVAR_01973882A → E in PARK2. 3 PublicationsCorresponds to variant dbSNP:rs55774500EnsemblClinVar.1
Natural variantiVAR_01973992A → V in PARK2. Corresponds to variant dbSNP:rs566229879Ensembl.1
Natural variantiVAR_019740100Q → H1 PublicationCorresponds to variant dbSNP:rs1256316516Ensembl.1
Natural variantiVAR_019741161K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 5 PublicationsCorresponds to variant dbSNP:rs137853057EnsemblClinVar.1
Natural variantiVAR_019742167S → N4 PublicationsCorresponds to variant dbSNP:rs1801474EnsemblClinVar.1
Natural variantiVAR_054107192M → L in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019743192M → V in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019744211K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2. 5 PublicationsCorresponds to variant dbSNP:rs137853060EnsemblClinVar.1
Natural variantiVAR_019746212C → Y in PARK2. 2 PublicationsCorresponds to variant dbSNP:rs137853058EnsemblClinVar.1
Natural variantiVAR_019747240T → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019748240T → R in PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization. 6 PublicationsCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019749253C → Y in PARK; late onset. 1 PublicationCorresponds to variant dbSNP:rs747427602Ensembl.1
Natural variantiVAR_019750256R → C in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP and ZNF746; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 7 PublicationsCorresponds to variant dbSNP:rs150562946Ensembl.1
Natural variantiVAR_019751271R → S1 Publication1
Natural variantiVAR_019752275R → W in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP; abolishes p53/TP53 transcriptional repression. 11 PublicationsCorresponds to variant dbSNP:rs34424986EnsemblClinVar.1
Natural variantiVAR_019753280D → N in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 PublicationsCorresponds to variant dbSNP:rs72480422Ensembl.1
Natural variantiVAR_019754284G → R in PARK2. Corresponds to variant dbSNP:rs751037529EnsemblClinVar.1
Natural variantiVAR_019755289C → G in PARK2; increased aggregation; fails to ubiquitinate SYT11; loses ability to bind SYT11; impaired relocalization to damaged mitochondria; loss of function in mitophagy. 3 PublicationsCorresponds to variant dbSNP:rs55961220Ensembl.1
Natural variantiVAR_062672311Q → R in a patient with Parkinson disease; unknown pathological significance. 1 Publication1
Natural variantiVAR_019756328G → E in PARK2; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 Publications1
Natural variantiVAR_019757334R → C2 PublicationsCorresponds to variant dbSNP:rs199657839EnsemblClinVar.1
Natural variantiVAR_019758339A → S1 Publication1
Natural variantiVAR_019759351T → P in PARK2; impairs folding of IBR domain. 2 Publications1
Natural variantiVAR_019760366R → W1 PublicationCorresponds to variant dbSNP:rs56092260EnsemblClinVar.1
Natural variantiVAR_062673371A → T in a patient with Parkinson disease; unknown pathological significance. 1 Publication