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PARK2 Gene

protein-coding   GIFtS: 69
GCID: GC06M161740

Parkin RBR E3 Ubiquitin Protein Ligase

(Previous names: Parkinson disease (autosomal recessive, juvenile) 2, parkin,...)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Parkin RBR E3 Ubiquitin Protein Ligase1 2     PDJ2 5
PRKN2 3 5     E3 Ubiquitin Ligase1
Parkinson Disease (Autosomal Recessive, Juvenile) 2, Parkin1 2     AR-JP2
Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin)1 2     E3 Ubiquitin-Protein Ligase Parkin2
Parkinson Juvenile Disease Protein 22 3     EC 6.3.2.-3
LPRS22 5     Parkinson Disease Protein 23

External Ids:    HGNC: 86071   Entrez Gene: 50712   Ensembl: ENSG000001853457   OMIM: 6025445   UniProtKB: O602603   

Export aliases for PARK2 gene to outside databases

Previous GC identifers: GC06M161122 GC06M161643 GC06M161678 GC06M159224


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PARK2 Gene:
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3
ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations
in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative
splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice
variants of this gene have been described but currently lack transcript support. (provided by RefSeq, Jul 2008)

GeneCards Summary for PARK2 Gene:
PARK2 (parkin RBR E3 ubiquitin protein ligase) is a protein-coding gene. Diseases associated with PARK2 include adenocarcinoma, ovarian, somatic, and parkinson disease, juvenile, type 2. GO annotations related to this gene include ubiquitin-protein ligase activity and identical protein binding.

UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260
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 (mitophagy), potentially by the ubiquitination of mitochondrial proteins. 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. 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. Independently of its ubiquitin ligase activity, protects from apoptosis
by the transcriptional repression of p53/TP53. 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. May represent a
tumor suppressor gene

Gene Wiki entry for PARK2 (Parkin) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000006.12  NC_018917.2  NT_025741.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the PARK2 gene promoter:
         GR   HNF-4alpha2   GR-alpha   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPARK2 promoter sequence
   Search Chromatin IP Primers for PARK2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PARK2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q25.2-q27   Ensembl cytogenetic band:  6q26   HGNC cytogenetic band: 6q25.2-q27

PARK2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PARK2 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M161740:  view genomic region     (about GC identifiers)

Start:
161,768,452 bp from pter      End:
163,148,834 bp from pter
Size:
1,380,383 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase parkin  
Size: 465 amino acids; 51641 Da
Subunit: 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. Interacts with CHPF, the interaction with isoform 2 may
facilitate PARK2 transport into the mitochondria. Interacts with MFN2 (phosphorylated), promotes PARK2
localization in dysfunctional depolarized mitochondria. Interacts with FBXO7; this promotes translocation to
dysfunctional depolarized mitochondria
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
Miscellaneous: 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)
5 PDB 3D structures from and Proteopedia for PARK2:
1IYF (3D)        2JMO (3D)        4BM9 (3D)        4I1F (3D)        4I1H (3D)    
Secondary accessions: A3FG77 A8K975 D3JZW7 D3K2X0 Q5TFV8 Q5VVX4 Q6Q2I6 Q8NI41 Q8NI43 Q8NI44
Q8WW07
Alternative splicing: 8 isoforms:  O60260-1   O60260-2   O60260-3   O60260-4   O60260-5   O60260-6   O60260-7   O60260-8   

Explore the universe of human proteins at neXtProt for PARK2: NX_O60260

Explore proteomics data for PARK2 at MOPED

Post-translational modifications: 

  • Auto-ubiquitinates in an E2-dependent manner leading to its own degradation. Also polyubiquitinated by RNF41 for
    proteasomal degradation1
  • S-nitrosylated. The inhibition of PARK2 ubiquitin E3 ligase activity by S-nitrosylation could contribute to the
    degenerative process in PD by impairing the ubiquitination of PARK2 substrates1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See PARK2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_004553.2  NP_054642.2  NP_054643.2  

    ENSEMBL proteins: 
     ENSP00000355865   ENSP00000355863   ENSP00000355862   ENSP00000355860   ENSP00000343589  
     ENSP00000434414   ENSP00000355858  
    Reactome Protein details: O60260

    PARK2 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    OriGene Protein Over-expression Lysate for PARK2
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    OriGene Custom Protein Services for PARK2
    GenScript Custom Purified and Recombinant Proteins Services for PARK2
    Novus Biologicals PARK2 Proteins
    Novus Biologicals PARK2 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for PARK2

    PARK2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of PARK2
    R&D Systems Antibodies for PARK2 (Parkin)
    Cell Signaling Technology (CST) Antibodies for PARK2 
    OriGene Antibodies for PARK2
    OriGene Custom Antibody Services for PARK2
    Novus Biologicals PARK2 Antibodies
    Abcam antibodies for PARK2
    Cloud-Clone Corp. Antibodies for PARK2
    ThermoFisher Antibody for PARK2
    LSBio Antibodies in human, mouse, rat for PARK2

    PARK2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for PARK2
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for PARK2
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for PARK2
    Cloud-Clone Corp. CLIAs for PARK2


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    PARK: Parkinson disease

    3 InterPro protein domains:
     IPR000626 Ubiquitin_dom
     IPR002867 Znf_C6HC
     IPR003977 Parkin

    Graphical View of Domain Structure for InterPro Entry O60260

    ProtoNet protein and cluster: O60260

    3 Blocks protein domains:
    IPB000626 Ubiquitin domain
    IPB002867 Zn-finger
    IPB003977 Parkin signature


    UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260
    Domain: The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes
    Domain: The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription (PubMed:19801972)
    Similarity: Belongs to the RBR family. Parkin subfamily
    Similarity: Contains 1 IBR-type zinc finger
    Similarity: Contains 3 RING-type zinc fingers
    Similarity: Contains 1 ubiquitin-like domain


    PARK2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PRKN2_HUMAN, O60260
    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 (mitophagy), potentially by the ubiquitination of mitochondrial proteins. 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. 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. Independently of its ubiquitin ligase activity, protects from apoptosis
    by the transcriptional repression of p53/TP53. 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. May represent a
    tumor suppressor gene
    Enzyme regulation: 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 (By similarity)

         Genatlas biochemistry entry for PARK2:
    parkin 2,protein expressed in the brain (substantia nigra),heart,testis,skeletal muscle located in the Golgi
    complex and the cytosol

         Enzyme Number (IUBMB): EC 6.3.2.-1

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842ubiquitin-protein ligase activity IDA15728840
    GO:0005515protein binding IPI10888878
    GO:0008270zinc ion binding IEA--
    GO:0016881acid-amino acid ligase activity ----
    GO:0019900kinase binding IPI17512523
         
    PARK2 for ontologies           About GeneDecksing


    Phenotypes:
         12 MGI mutant phenotypes (inferred from 9 alleles(MGI details for Park2):
     behavior/neurological  cardiovascular system  cellular  growth/size/body  homeostasis/metabolism 
     integument  mortality/aging  muscle  nervous system  no phenotypic analysis 
     respiratory system  skeleton 

    PARK2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for PARK2: Park2tm1Tmd Park2tm1Shn Park2tm1Roo Park2tm1Ykt Park2tm1Jfe Park2tm1Ccs
                                                         Park2tm1Rpa

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PARK2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for PARK2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PARK2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PARK2

    miRNA
    Products:
        
    miRTarBase miRNAs that target PARK2:
    hsa-mir-335-5p (MIRT016831), hsa-mir-26b-5p (MIRT028924)

    Block miRNA regulation of human, mouse, rat PARK2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PARK2 (see all 14):
    hsa-miR-4324 hsa-miR-26a-2* hsa-miR-576-5p hsa-miR-607 hsa-miR-181c hsa-miR-4263 hsa-miR-181a hsa-miR-181d
    SwitchGear 3'UTR luciferase reporter plasmidPARK2 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for PARK2
    Predesigned siRNA for gene silencing in human, mouse, rat PARK2

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for PARK2

    Clone
    Products:
         
    OriGene clones in human, mouse for PARK2 (see all 18)
    OriGene ORF clones in mouse, rat for PARK2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): PARK2 (NM_004562)
    Sino Biological Human cDNA Clone for PARK2
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PARK2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PARK2

    Cell Line
    Products:
         
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    Browse ESI BIO Cell Lines and PureStem Progenitors for PARK2 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PARK2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PRKN2_HUMAN, O60260: Cytoplasm, cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Note=Mainly localizes in
    the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies.
    Mitochondrial localization gradually increases with cellular growth. Also relocates to dysfunctional mitochondria
    that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1-dependent
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    endoplasmic reticulum5
    golgi apparatus5
    mitochondrion5
    nucleus5
    cytoskeleton2
    endosome2
    lysosome2
    plasma membrane2
    vacuole2
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000151ubiquitin ligase complex IDA--
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IDA17512523
    GO:0005739mitochondrion IMP19029340
    GO:0005783endoplasmic reticulum IEA--

    PARK2 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for PARK2 About   (see all 11)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Class I MHC mediated antigen processing and presentation
    Class I MHC mediated antigen processing and presentation0.84
    Adaptive Immune System0.41
    Antigen processing- Ubiquitination and Proteasome degradation0.84
    Ubiquitin mediated proteolysis0.35
    2Parkin-Ubiquitin Proteasomal System pathway
    Proteolysis Role of Parkin in the Ubiquitin Proteasomal Pathway0.89
    Parkin-Ubiquitin Proteasomal System pathway0.89
    3Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
    Parkinson's disease0.57
    4Inactivation of APC/C via direct inhibition of the APC/C complex
    Common schema of ubiquitination0.33
    5CDK-mediated phosphorylation and removal of Cdc6
    Parkinson's Disease Pathway0.31

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for PARK2
        Parkinson's Disease Pathway

    2 Cell Signaling Technology (CST) Pathways for PARK2
        Neuroscience
    Protein Stability

    2 GeneGo (Thomson Reuters) Pathways for PARK2
        Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway
    Proteolysis Putative ubiquitin pathway

    3 BioSystems Pathways for PARK2
        Parkin-Ubiquitin Proteasomal System pathway
    Parkinsons Disease Pathway
    Alpha-synuclein signaling


    1 Reactome Pathway for PARK2
        Antigen processing: Ubiquitination & Proteasome degradation


    3 Kegg Pathways  (Kegg details for PARK2):
        Ubiquitin mediated proteolysis
    Protein processing in endoplasmic reticulum
    Parkinson's disease

    UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260
    Pathway: Protein modification; protein ubiquitination


    PARK2 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PARK2: 

              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Parkinson's Disease in human mouse rat
              Autophagy in human mouse rat
              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PARK2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PARK2 (O602601, 2, 3 ENSP000003558654) via UniProtKB, MINT, STRING, and/or I2D (see all 141)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HSPA1AP081073, ENSP000003648024I2D: score=1 STRING: ENSP00000364802
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    ENSG00000231555P081073I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 23):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000209protein polyubiquitination IDA16227987
    GO:0000422mitochondrion degradation IMP19029340
    GO:0001933negative regulation of protein phosphorylation IDA17512523
    GO:0006351transcription, DNA-templated IEA--
    GO:0006355regulation of transcription, DNA-templated IEA--

    PARK2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for PARK2 (PRKN2)

    5 HMDB Compounds for PARK2    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    CalciumCa (see all 2)7440-70-2--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    Selected Novoseek inferred chemical compound relationships for PARK2 gene (see all 56)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    mg 132 60.5 7 10976934 (1), 18586549 (1), 20171192 (1)
    rotenone 56.3 19 17587308 (2), 19074146 (2), 15198987 (1), 16517603 (1) (see all 12)
    dopamine 51 125 15492001 (6), 16000163 (5), 15198987 (4), 12915482 (4) (see all 44)
    levodopa 50.9 24 16000163 (6), 18228569 (2), 15896322 (2), 16447759 (2) (see all 11)
    lactacystin 49.3 8 12928331 (2), 15973159 (2), 16130151 (2), 18040862 (1)
    tyrosine 33 16 19620960 (2), 18197257 (1), 16002472 (1), 16387660 (1) (see all 15)
    mptp 32.2 7 17105905 (1), 16375772 (1), 11241385 (1), 16672220 (1) (see all 5)
    lysine 27.4 11 15718234 (4), 17873885 (1), 15132984 (1), 17869110 (1) (see all 6)
    tunicamycin 27.3 8 17465879 (1), 12588799 (1), 12686385 (1), 17481813 (1) (see all 5)
    zinc 23.9 5 20302514 (4), 12485996 (1)



    PARK2 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for PARK2 gene (3 alternative transcripts): 
    NM_004562.2  NM_013987.2  NM_013988.2  

    Unigene Cluster for PARK2:

    Parkinson protein 2, E3 ubiquitin protein ligase (parkin)
    Hs.132954  [show with all ESTs]
    Unigene Representative Sequence: NM_004562
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000366898(uc011egf.2 uc003qtv.4 uc003qtw.4 uc010kkd.3 uc003qtx.4 uc021zhs.1 uc021zht.1 uc003qty.4 uc003qtz.4 uc021zhu.1 uc021zhv.1 uc021zhw.1 uc021zhx.1 uc021zhy.1)
    ENST00000366897 ENST00000366896 ENST00000366894 ENST00000338468 ENST00000479615
    ENST00000366892(uc010kke.1)
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Selected qRT-PCR Assays for microRNAs that regulate PARK2 (see all 14):
    hsa-miR-4324 hsa-miR-26a-2* hsa-miR-576-5p hsa-miR-607 hsa-miR-181c hsa-miR-4263 hsa-miR-181a hsa-miR-181d
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    Additional mRNA sequence: 

    AB009973.1 AB245403.1 AF381282.1 AF381284.1 AK292590.1 AK294684.1 BC022014.2 EF375726.1 
    GU345837.1 GU345838.1 GU345839.1 GU345840.1 GU357501.1 GU357502.1 GU361466.1 GU361467.1 
    GU361468.1 GU361469.1 GU361470.1 GU361471.1 

    9 DOTS entries:

    DT.97786520  DT.100018005  DT.91754864  DT.99941242  DT.121333987  DT.121334055  DT.121333970  DT.97763953 
    DT.99942879 

    12 AceView cDNA sequences:

    AA176605 BM782100 BQ181930 AI818737 AA176878 BQ082313 NM_013988 AB009973 
    NM_004562 NM_013987 AF381286 BF679817 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    PARK2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATCACAGTA
    PARK2 Expression
    About this image

    PARK2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PARK2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.132954

    UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260
    Tissue specificity: 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)

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PARK2: 
              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Parkinson's Disease in human mouse rat
              Autophagy in human mouse rat
              Ubiquitin Ligases in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for PARK2 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Park21 , 5 Parkinson disease (autosomal recessive, juvenile) 2, more1, 5 83.41(n)1
    83.84(a)1
      17 (7.80 cM)5
    508731  NM_016694.31  NP_057903.11 
     108403845 
    chicken
    (Gallus gallus)
    Aves PARK21 parkinson protein 2, E3 ubiquitin protein ligase (parkin) 72.78(n)
    74.89(a)
      421577  XM_004935556.1  XP_004935613.1 
    lizard
    (Anolis carolinensis)
    Reptilia PARK26
    parkin RBR E3 ubiquitin protein ligase
    80(a)
    1 ↔ 1
    1(211240747-211564097)
    zebrafish
    (Danio rerio)
    Actinopterygii park21 Parkinson disease (autosomal recessive, juvenile) 2, more 64.25(n)
    63.6(a)
      550328  NM_001017635.1  NP_001017635.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta parkin3
    park1
    parkin1 42(a)3
    53.82(n)1
    45.35(a)1
      3 78C23
    403361  NM_168885.31  NP_730601.11 
    worm
    (Caenorhabditis elegans)
    Secernentea pdr-11 pdr-1 46.03(n)
    35.07(a)
      176816  NM_067445.6  NP_499846.2 


    ENSEMBL Gene Tree for PARK2 (if available)
    TreeFam Gene Tree for PARK2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PARK2 gene
    Selected SIMAP similar genes for PARK2 using alignment to 13 protein entries:     PRKN2_HUMAN (see all proteins) (see all similar genes):
    RHBG    ZNF554    ARL6IP5    PFKFB3    EIF3K    LSM12
    AAMDC    C1orf143    TNNT1    ZNF799    CALCOCO2    CCDC151
    GNB2L1    MRPL45    SEPSECS    SMYD4    ZNF85    AARSD1

    PARK2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for PARK2 (see all 33229)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1499538141,2,,4
    C,FParkinson disease 2 (PARK2)4 --161778957(+) GCTGCG/AGACAC 6 /P /L mis12Minor allele frequency- A:0.00NA EU 5479
    rs344249861,2,,4
    C,FParkinson disease (PARK)4 pathogenic1162214446(-) ATGATC/TGGCAG 6 R W mis13Minor allele frequency- T:0.00NA EU 5877
    rs1505629461,2,,4
    C,FParkinson disease (PARK)4 --162214503(+) GTGGCG/AGGAGT 6 /R /C mis12Minor allele frequency- A:0.00NA EU 5873
    rs557745001,2,,4
    C,FParkinson disease 2 (PARK2)4 pathogenic1162691657(-) GAATGC/AAACTG 5 /E /A int1 mis12Minor allele frequency- A:0.00NA EU 5875
    rs1489901381,2,,4
    C,FParkinson disease 2 (PARK2)4 --162872242(+) CAGCCG/AGAACC 6 /P /L mis12Minor allele frequency- A:0.00NA EU 5875
    VAR_0197644
    Parkinson disease 2 (PARK2)4--see VAR_0197642 G D mis40--------
    VAR_0197414
    Parkinson disease 2 (PARK2)4--see VAR_0197412 K N mis40--------
    VAR_0700784
    Parkinson disease 2 (PARK2)4--see VAR_0700782 V E mis40--------
    VAR_0197444
    Parkinson disease 2 (PARK2)4--see VAR_0197442 K N mis40--------
    VAR_0197654
    Parkinson disease 2 (PARK2)4--see VAR_0197652 C F mis40--------

    HapMap Linkage Disequilibrium report for PARK2 (161768452 - 162018452 bp, first 250kb of PARK2)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for PARK2 (see all 235):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2661823CNV Deletion23128226
    esv2008419CNV Deletion18987734
    esv2567515CNV Deletion19546169
    esv2673918CNV Deletion23128226
    esv2661906CNV Deletion23128226
    esv2673412CNV Deletion23128226
    esv1995879CNV Deletion18987734
    esv2673491CNV Deletion23128226
    esv2676221CNV Deletion23128226
    dgv1078e201CNV Deletion23290073

    Human Gene Mutation Database (HGMD): PARK2
    Locus Specific Mutation Databases (LSDB): PARK2

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602544   
    OMIM disorders: 600116  211980  167000  607572  
    UniProtKB/Swiss-Prot: PRKN2_HUMAN, O60260
  • Parkinson disease (PARK) [MIM:168600]: A 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. Note=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)
  • Parkinson disease 2 (PARK2) [MIM:600116]: A 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. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Note=Defects in PARK2 may be involved in the development and/or progression of ovarian cancer

  • Selected diseases for PARK2 (see all 97):    About MalaCards
    adenocarcinoma, ovarian, somatic    parkinson disease, juvenile, type 2    parkin type of early-onset parkinson disease    autosomal recessive juvenile parkinson disease
    leprosy    adenocarcinoma of lung, somatic    limb-girdle muscular dystrophy type 2h    parkinson's disease
    parkinson disease 1    focal dystonia    classic rett syndrome    parkinson disease 10
    tremor    lafora disease    essential tremor    bell's palsy
    hypersomnia    thanatophoric dysplasia    amyotrophic lateral sclerosis-parkinsonism/dementia complex    rett syndrome

    3 diseases from the University of Copenhagen DISEASES database for PARK2:
    Parkinson's disease     Progressive myoclonus epilepsy     Cancer

    PARK2 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for PARK2 gene (see all 69)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    parkinsonism juvenile autosomal recessive 96.7 91 15022188 (2), 16002472 (2), 16672220 (2), 11128608 (2) (see all 71)
    autosomal recessive parkinsonism 92.5 24 12707451 (2), 17914725 (1), 18307263 (1), 19297401 (1) (see all 19)
    parkinson disease 90 368 16914382 (4), 17499497 (4), 16227987 (3), 16401616 (3) (see all 99)
    parkinsonism 86.9 162 16375772 (5), 15725358 (5), 18546294 (4), 15642853 (4) (see all 95)
    neurodegenerative diseases 73.8 11 16908979 (1), 19483198 (1), 12676955 (1), 16447778 (1) (see all 12)
    lgmd2h 72.5 2 15316618 (1), 16816390 (1)
    autosomal dominant parkinsonism 71.4 3 11455179 (2), 10894217 (1)
    parkinson disease, autosomal dominant 70.8 7 18446261 (1), 15717024 (1), 18292964 (1), 12761037 (1) (see all 6)
    neurodegeneration 68.9 42 15603737 (3), 16597723 (2), 15911761 (2), 19741132 (2) (see all 29)
    movement disorders 66.2 7 15266615 (1), 11334819 (1), 12972409 (1), 15725358 (1) (see all 6)

    Genatlas disease: PARK2
    Parkinson disease,juvenile,autosomal recessive,without Lewy bodies,but with selective degeneration of nigral
    dopaminergic neurons and gliosis of substantia nigra and locus ceruleus,DOPA responsive

    GeneTests: PARK2
    GeneReviews: PARK2
    Genetic Association Database (GAD): PARK2
    Human Genome Epidemiology (HuGE) Navigator: PARK2 (103 documents)

    Export disorders for PARK2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PARK2 gene, integrated from 10 sources (see all 1243):
    (articles sorted by number of sources associating them with PARK2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Parkin mutations are rare in patients with young-onset parkinsonism in a US population. (PubMed id 12781599)1, 2, 4, 9 Chen R.... Chan P. (Parkinsonism Relat. Disord. 2003)
    2. Novel parkin mutations detected in patients with early-onset Parkinson's disease. (PubMed id 15584030)1, 2, 4, 9 Bertoli-Avella A.M....Bonifati V. (Mov. Disord. 2005)
    3. Association between early-onset Parkinson's disease and mutations in the parkin gene. (PubMed id 10824074)1, 2, 4, 9 Luecking C.B....Brice A. (N. Engl. J. Med. 2000)
    4. Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations. (PubMed id 11971093)1, 2, 4 Hedrich K.... Klein C. (Neurology 2002)
    5. Role of parkin mutations in 111 community-based patients with early- onset parkinsonism. (PubMed id 12112109)1, 2, 4 Kann M.... Klein C. (Ann. Neurol. 2002)
    6. Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism. (PubMed id 12397156)1, 2, 4 Munoz E.... Oliva R. (J. Neurol. Neurosurg. Psych. 2002)
    7. Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson's disease. (PubMed id 10511432)1, 2, 4 Satoh J. and Kuroda Y. (NeuroReport 1999)
    8. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. (PubMed id 9560156)1, 2, 3 Kitada T.... Shimizu N. (Nature 1998)
    9. parkin mutation analysis in clinic patients with early-onset Parkinson [corrected] disease. (PubMed id 15266615)1, 4, 9 Poorkaj P....Payami H. (Am. J. Med. Genet. A 2004)
    10. Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. (PubMed id 19801972)1, 2, 9 da Costa C.A....Checler F. (Nat. Cell Biol. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5071 HGNC: 8607 AceView: PARK2 Ensembl:ENSG00000185345 euGenes: HUgn5071
    ECgene: PARK2 Kegg: 5071 H-InvDB: PARK2

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for PARK2 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=PARK2[genesymbol]
    Protein Spotlighthttp://web.expasy.org/spotlight/back_issues/131

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PARK2 gene:
    Search GeneIP for patents involving PARK2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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