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Relevance to Autism

In a genome-wide study, association was found between CNVs in the PARK2 gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a rare duplication in the PARK2 gene has been identified in an individual with ASD (Oâ??Roak et al., 2012). As well, rare variants in the PARK2 gene have been identified in individuals with autosomal recessive juvenile parkinsonism (Kitada et al., 1998).

Molecular Function

Ubiquitin-protein ligase

External Links

       

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
ASD
Support
Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder.
ADHD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders.
ASD
ID
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Highly Cited
An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin.
Highly Cited
Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson\'s disease.
Highly Cited
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.
Highly Cited
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
ARJP
Recent Recommendation
Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin.
Recent Recommendation
Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN188R001 
 Deletion 
 N/A 
 N/A 
 De novo 
  
  
 GEN188R002 
 Deletion 
 N/A 
 N/A 
 Familial 
 Paternal 
 Multiplex 
 GEN188R003 
 Duplication 
 N/A 
 N/A 
 Familial 
 Paternal 
 Simplex 
 GEN188R004 
 Deletion 
  
  
 Familial 
 Paternal 
 Unknown 
 GEN188R005 
 Deletion 
  
  
 Unknown 
  
 Unknown 
 GEN188R006 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R007 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R008 
 Deletion 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R009 
 Deletion 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R010 
 Deletion 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R011 
 Deletion 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN188R012 
 Deletion 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R013 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R014 
 Deletion 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R015 
 Deletion 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R016 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R017 
 Deletion 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN188R018 
 Deletion 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN188R019 
 Duplication 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN188R020 
 Duplication 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R021 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R022 
 Duplication 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R023 
 Duplication 
  
  
 De novo 
  
 Simplex 
 GEN188R024 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R025 
 Deletion 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN188R026 
 Duplication 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN188R027 
 Duplication 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R028 
 Deletion 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN188R029 
 Deletion 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN188R030 
 Duplication 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN188R031 
 Deletion 
  
  
 Unknown 
  
 Simplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN188C001 
 Deletion 
  
 N/A 
 N/A 
 AGRE, ACC 
 Discovery 
 GEN188C002 
 Deletion-Duplication 
  
  
  
 Germany 
 Discovery 
 GEN188C003 
 Deletion-Duplication 
  
  
  
 Germany 
 Replication 



Model Summary

Elucidate the role of impairment of mitochondrial function in Parkinson Disease pathogenesis

External Links

AllenBrainAtlas   MGI Logo  Entrez Gene

References

Type
Title
Author, Year
Primary
Mono- and double-mutant mouse models of Parkinson\'s disease display severe mitochondrial damage.

PARK2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of parkin exon 3 resulting in frameshift after amino acid 57 of parkin
Allele Type: Targeted (Knock Out)
Strain of Origin: 129Sv/J
Genetic Background: C57BL/6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PARK2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mitochondrial respiration1
Decreased
Description: Decreased mitochondrial respiration of Complex I in the presence of the uncouple CCCP
Exp Paradigm: Mitochondria measurement of respiration in slices of Substantia nigra in the presence of CCCP
 Respiration capacity of mitochondria
 Unreported
Brain Ultrasctructure1
Abnormal
Description: Abnormal brain ultrastructure characterized by cytoplasmic vacuoles, disruption of golgi network, endoplasmic reticulum, abnormal mitochondria - electron dense inclusion bodies, dilated and disorganzied cristae
Exp Paradigm: Electron microscopy of the Substantia Nigra, the striatum, and the Cortex
 Electron Microscopy
 12-14 months
Brain Ultrasctructure1
Abnormal
Description: Abnromal brain ultrastructure characterized by abnormal mitochondria and lipfouscin granules within dopaminergic neurons in the Substantia Nigra
Exp Paradigm: Electron microscopy with immunogold technique in the substantia nigra
 Electron Microscopy
 12-14 months
General Characteristics1
 No Change
 General Observations
 Unreported
Mitochondrial respiration1
 No Change
 Respiration capacity of mitochondria
 Unreported
Mitochondrial respiration1
 No Change
 Respiration capacity of mitochondria
 Unreported
Brain Anatomy1
 No Change
 Macroscopical analysis
 Unreported
Brain Mitochondria Morphology1
 No Change
 Quantitative analysis
 12-14 months
Brain Morphology1
 No Change
 Immunohistochemical and histological analysis
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Homeostasis ,   Immune Response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  



Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABL1 c-abl oncogene 1, non-receptor tyrosine kinase 25 P00519 2-D gel electrophoresis
GST
in vitro kinase assay
IP/WB (mouse brain)
IP/WB (SH-SY5Y cells)
MS
WB (SH-SY5Y cells)
Ko HS 2010
AIMP2 aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 7965 Q13155 in vitro ubiquitination assay (SH-SY5Y cells)
IP/WB (COS-7 cells)
Y2H
Corti O 2003
BACH1 BTB and CNC homology 1, basic leucine zipper transcription factor 1 571 O14867 IP/WB (NIH-3T3 cells)
Zenke-Kawasaki Y 2007
CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) 834 P43527 WB (HEK293T cells)
WB (MCF-7 cells)
Kahns S 2003
CASP8 caspase 8, apoptosis-related cysteine peptidase 841 Q14790 WB (HEK293T cells)
WB (Jurkat T cells)
WB (MCF-7 cells)
Kahns S 2003
CCNE1 cyclin E1 898 P24864 in vitro ubiquitination assay
nickel-agarose pull-down (insect cells)
Staropoli JF 2003
CDK5 cyclin-dependent kinase 5 1020 Q00535 IP/WB (HEK293 cells)
IP/WB (rat brain)
metabolic labeling with 32P (GST fusion proteins)
metabolic labeling with 32P (HEK293 cells)
metabolic labeling with 32P (SH-SY5Y cells)
WB (HEK293 cells)
Avraham E 2007
CUL1 cullin 1 8454 Q13616 GST
IP/WB (HeLa cells)
IP/WB (human brain)
nickel-agarose pull-down (insect cells)
Staropoli JF 2003
DNAJA1 DnaJ (Hsp40) homolog, subfamily A, member 1 3301 P31689 IP/WB (HEK293T cells)
IP/WB (human brain)
IP/WB (SH-SY5Y cells)
Imai Y 2002
DNAJB1 DnaJ (Hsp40) homolog, subfamily B, member 1 3337 P25685 IP/WB (HEK293T cells)
Imai Y 2002
FBXW7 ?F-box and WD repeat domain containing 7 55294 Q969H0 GST
IP/WB (HeLa cells)
IP/WB (human brain)
IP/WB (mouse brain)
Staropoli JF 2003
GPR37 G protein-coupled receptor 37 (endothelin receptor type B-like) 2861 O15354 in vitro ubiquitination assay (SH-SY5Y cells)
IP/WB (HEK293T cells)
IP/WB (human brain)
IP/WB (SH-SY5Y cells)
WB (SH-SY5Y cells)
Imai Y 2001
HEXDC hexosaminidase (glycosyl hydrolase family 20, catalytic domain) containing 284004 Q8WVB3 Y2H
Stelzl U 2005
HSPA4 heat shock 70kDa protein 4 3308 P34932 IP/WB (HEK293T cells)
IP/WB (human brain)
IP/WB (SH-SY5Y cells)
Imai Y 2002
HSPA8 heat shock 70kDa protein 8 3312 P11142 IP/WB (HEK293T cells)
IP/WB (human brain)
IP/WB (SH-SY5Y cells)
Imai Y 2002
LIMK1 LIM domain kinase 1 3984 P53667 in vitro ubiquitination assay
IP/WB (HEK293 cells)
Lim MK 2007
LRRK2 leucine-rich repeat kinase 2 120892 Q5S007 IP/WB (HEK293T cells)
Smith WW 2005
MAPT microtubule-associated protein tau 4137 P10636 IP/WB (HEK293 cells)
Petrucelli L 2004
NDUFA4L2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 56901 Q9NRX3 Y2H
Stelzl U 2005
PAFAH1B2 platelet-activating factor acetylhydrolase 1b, catalytic subunit 2 (30kDa) 5049 P68402 Y2H
Stelzl U 2005
PARK2 parkinson protein 2, E3 ubiquitin protein ligase (parkin) 5071 O60260 in vitro ubiquitination assay (GST-parkin)
Hampe C 2006
PARK7 Parkinson disease (autosomal recessive, early onset) 7 11315 Q99497 IP/WB (SH-SY5Y cells)
Moore DJ 2005
PDCD2 programmed cell death 2 5134 Q16342 in vitro ubiquitination assay (COS-1 cells)
IP/WB (COS-1 cells)
Fukae J 2009
PINK1 PTEN induced putative kinase 1 65018 Q9BXM7 affinity chromatography (purified proteins)
IP/WB (COS-1 cells)
IP/WB (SH-SY5Y cells)
Shiba K 2009
PLCG1 phospholipase C, gamma 1 5335 P19174 IP/WB (human brain)
IP/WB (SH-SY5Y cells)
Dehvari N 2009
PSMA1 proteasome (prosome, macropain) subunit, alpha type, 1 5682 P25786 IP/WB (SH-SY5Y cells)
Imai Y 2002
PSMA4 ?proteasome (prosome, macropain) subunit, alpha type, 4 5685 P25789 IP/WB (HEK293 cells)
IP/WB (PC12 cells)
Y2H
Dächsel JC 2005
PSMC5 proteasome (prosome, macropain) 26S subunit, ATPase, 5 5705 P62195 IP/WB (HEK293 cells)
Tsai YC 2003
RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) 5879 A4D2P1 Y2H
Stelzl U 2005
RAD1 RAD1 homolog (S. pombe) 5810 O60671 Y2H
Stelzl U 2005
RANBP2 RAN binding protein 2 5903 P49792 GST (HEK293 cells)
in vitro ubiquitination assay
IP/WB (HEK293 cells)
IP/WB (SH-SY5Y cells)
Y2H
Um JW 2006
RGS2 regulator of G-protein signaling 2, 24kDa 5997 P41220 Y2H
Stelzl U 2005
RNF41 ring finger protein 41 10193 Q9H4P4 in vitro binding assay
IP/WB (C33-A cells)
Y2H
Zhong L 2005
SEPT5 septin 5 5413 Q99719 in vitro ubiquitination assay
IP/WB (HEK293 cells)
IP/WB (human brain)
Y2H
Choi P 2003
SIM2 ?single-minded homolog 2 (Drosophila) 6493 Q14190 IP/WB (HEK293 cells)
Okui M 2005
Slc6a3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 13162 Q61327 IP/WB (HEK293 cells)
WB (HEK293 cells)
Jiang H 2004
SNCA synuclein, alpha (non A4 component of amyloid precursor)? 6622 P37840 IP/WB (BE-M17 cells)
IP/WB (human brain)
Choi P 2001
SNCAIP synuclein, alpha interacting protein 9627 Q9Y6H5 in vitro ubiquitination assay
IP/WB (HEK293 cells)
IP/WB (rat brain)
WB (HEK293 cells)
Chung KK 2001
STUB1 STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase 10273 Q9UNE7 IP/WB (HEK293T cells)
IP/WB (human brain)
IP/WB (SH-SY5Y cells)
Imai Y 2002
SYT11 synaptotagmin XI 23208 Q9BT88 IP/WB (human brain)
IP/WB HEK293 cells
WB (HEK293 cells)
Y2H
Huynh DP 2003
TRIP13 thyroid hormone receptor interactor 13 9319 Q15645 Y2H
Rual JF 2005
UBC ubiquitin C? 7316 P63279 IP/WB (SH-SY5Y cells)
Sriram SR 2005
UBE2G1 ubiquitin-conjugating enzyme E2G 1 (UBC7 homolog, yeast) 7326 P62253 IP/WB (HEK293T cells)
Imai Y 2001
UBE2J1 ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog, yeast) 51465 Q9Y385 IP/WB (HEK293T cells)
Imai Y 2001
UBE2L3 ?ubiquitin-conjugating enzyme E2L 3 7332 P68036 IP/WB (HEK293 cells)
Shimura H 2000
UBE2L6 ubiquitin-conjugating enzyme E2L 6? 9246 O14933 IP/WB (HEK293 cells)
Zhang Y 2000
YWHAH tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide? 7533 Q04917 IP/WB (HEK293 cells)
IP/WB (mouse brain)
Sato S 2006
Dlg1 discs, large homolog 1 (Drosophila) 13383 Q811D0 fluorescence polarization
Stiffler MA 2006
Rgs3 regulator of G-protein signaling 3 50780 Q9DC04 fluorescence polarization
protein microarray
Stiffler MA 2006
CAMK2A calcium/calmodulin-dependent protein kinase II alpha 25400 P11275 IP/WB (rat brain)
Fallon L 2002
CASK ?calcium/calmodulin-dependent serine protein kinase (MAGUK family)? 29647 Q62915 GST
IP/WB (rat brain)
Fallon L 2002
Dlg4 discs, large homolog 4 (Drosophila) 29495 P31016 IP/WB (rat brain)
Fallon L 2002
Egfr epidermal growth factor receptor 13649 Q01279 IP/WB (Her14 cells)
Fallon L 2006
EPS15 epidermal growth factor receptor pathway substrate 15 13858 P42567 GST (HEK293 cells)
GST (rat brain)
in vitro ubiquitination assay
nickel-agarose pull-down (COS-7 cells)
Fallon L 2006
GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B 24410 Q00960 IP/WB (rat brain)
Fallon L 2002
HOMER1 homer homolog 1 (Drosophila) 29456 Q9Z214 IP/WB (rat brain)
Fallon L 2002
TUBA1A tubulin, alpha 1A 7846 Q71U36 IP/WB (HEK293 cells)
IP/WB (rat brain)
WB (HEK293 cells)
WB (rat brain)
Ren Y 2003
TUBB tubulin, beta? 203068 P07437 IP/WB (HEK293 cells)
IP/WB (rat brain)
WB (HEK293 cells)
WB (rat brain)
Ren Y 2003
TUBG1 ?tubulin, gamma 1 7283 P23258 IP/WB (HEK293 cells)
IP/WB (rat brain)
Zhao J 2003
eIF-4E Eukaryotic initiation factor 4E 45525 P48598 Ottone C 2011

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