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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 t... See more...
Aliases for PRKN Gene
Aliases for PRKN Gene
External Ids for PRKN Gene
- HGNC: 8607
- Entrez Gene: 5071
- Ensembl: ENSG00000185345
- OMIM: 602544
- UniProtKB: O60260
Previous HGNC Symbols for PRKN Gene
- PARK2
Summaries for PRKN 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 PRKN Gene
PRKN (Parkin RBR E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with PRKN include Parkinson Disease 2, Autosomal Recessive Juvenile and Ovarian Cancer. Among its related pathways are Neuroscience and Metabolism of proteins. An important paralog of this gene is ANKIB1.
UniProtKB/Swiss-Prot Summary for PRKN Gene
-
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, SEPTIN5, 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, PubMed:29311685). 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.
Additional gene information for PRKN Gene
- HGNC(8607)
- Entrez Gene(5071)
- Ensembl(ENSG00000185345)
- OMIM(602544)
- UniProtKB(O60260)
- Open Targets Platform(ENSG00000185345)
- Monarch Initiative
- Search for PRKN at DataMed
- Search for PRKN at HumanCyc
No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PRKN Gene
Genomics for PRKN Gene
GeneHancer (GH) Regulatory Elements Pubs
Promoters and enhancers for PRKN Gene
| GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
|---|---|---|---|---|---|---|---|---|---|---|
| GH06J162726 | Promoter/Enhancer | 2.1 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | 0.0 | -13 | 2.4 | CREB1 GATAD2A HNRNPL ATF7 PRDM10 ZNF629 TFE3 RFX1 SIX5 ZNF692 | PACRG PRKN piR-57133-533 QKI | |
| GH06J162705 | Enhancer | 0.5 | ENCODE | 12.1 | +21.4 | 21438 | 1.2 | ZIC2 POLR2A YY1 NR2F2 SPI1 | PACRG PRKN RF00017-5932 piR-58929-099 | |
| GH06J162363 | Enhancer | 1 | Ensembl ENCODE | 4.5 | +363.4 | 363413 | 1.2 | LEF1 ZNF24 ZNF740 EP300 MGA CBX3 ZNF766 E2F5 NR2C2 ZBTB11 | PACRG PRKN RF00994-972 piR-41399-422 | |
| GH06J162442 | Enhancer | 0.6 | Ensembl ENCODE | 5.5 | +285.1 | 285101 | 1.8 | CTCF TEAD4 RAD21 RFX1 SMC3 ZNF654 | PRKN LOC105369171 KRT8P44 PACRG | |
| GH06J162409 | Enhancer | 0.7 | Ensembl ENCODE CraniofacialAtlas | 4.9 | +317.9 | 317901 | 5 | KDM1A GATA2 | PRKN PACRG LOC105369171 RF00994-972 |
- Elite GeneHancer and/or Elite GeneHancer-gene association
Download GeneHancer data from 2017 publication |
Request up-to-date GeneHancer data (full dataset)
GeneHancers around PRKN on the GeneHancer Hub at the UCSC Golden Path
Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PRKN
Genomic Locations for PRKN Gene
Genomic Locations for PRKN Gene
- chr6:161,347,417-162,727,802
- (GRCh38/hg38)
- Size:
- 1,380,386 bases
- Orientation:
- Minus strand
- chr6:161,768,452-163,148,834
- (GRCh37/hg19)
- Size:
- 1,380,383 bases
- Orientation:
- Minus strand
Genomic View for PRKN Gene
Genes around PRKN on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 6q26 by HGNC
- 6q26 by Entrez Gene
- 6q26 by Ensembl
PRKN Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for PRKN Gene
Proteins for PRKN Gene
-
Protein details for PRKN Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- O60260-PRKN_HUMAN
- Recommended name:
- E3 ubiquitin-protein ligase parkin
- Protein Accession:
- O60260
- A3FG77
- A8K975
- D3JZW7
- D3K2X0
- Q5TFV8
- Q5VVX4
- Q6Q2I6
- Q8NI41
- Q8NI43
- Q8NI44
- Q8WW07
Protein attributes for PRKN Gene
- Size:
- 465 amino acids
- Molecular mass:
- 51641 Da
- Quaternary structure:
-
- 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 SEPTIN5. 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).
- 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.
Three dimensional structures from OCA and Proteopedia for PRKN Gene
Post-translational modifications for PRKN Gene
- Auto-ubiquitinates in an E2-dependent manner leading to its own degradation (PubMed:19229105). Also polyubiquitinated by RNF41 for proteasomal degradation.
- 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.
- Phosphorylation at Ser-65 by PINK1 contributes to activate PRKN activity. It is however not sufficient and requires binding to phosphorylated ubiquitin as well.
- Modification sites at PhosphoSitePlus
- Modification sites at neXtProt
Other Protein References for PRKN Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
- LifeSpan BioSciences PARK2 / Parkin 2 Antibody (LS-B5889) and PARK2 / Parkin 2 Antibody (LS-B13850)
- G Biosciences Immunotag™ PARK2 Antibody and Immunotag™ Parkin Antibody
- NSJ Bioreagents Parkin Antibody
- Creative Diagnostics Anti-Parkin monoclonal antibody, clone 2B2
- GeneTex Anti-Parkin antibody [PRK8] and Anti-Parkin antibody
-
Custom Antibody ServicesOriGene Antibodies for PRKN
- Novus Biologicals Antibodies for PRKN
-
Abcam antibodies for PRKN
- Invitrogen Antibodies for PRKN (AFLGC-PRKN)
-
Boster Bio Antibodies for PRKN
-
Custom Antibody ServicesProSci Antibodies for PRKN
- Sino Biological Antibodies for PRKN
Protein Products
- Creative Biomart Recombinant Human PARK2
- Search Origene for MassSpec and Protein Over-expression Lysates for PRKN
- Origene Custom Protein Services for PRKN
- ProSpec Recombinant Proteins for PRKN
-
ProSci Proteins for PRKN
-
Abcam proteins for PRKN
Assay Products
- RayBiotech Custom Human Parkin ELISA
- antibodies-online: Show 21 available PARK2 Elisa Kits ranked by validation data
- Compare Top PARK2 Elisa Kits
-
Quality Products:
-
Boster Bio ELISA Kits for PRKN
-
Abcam assays for PRKN
No data available for DME Specific Peptides for PRKN Gene
Domains & Families for PRKN Gene
Gene Families for PRKN Gene
- HGNC:
- Human Protein Atlas (HPA):
-
- Disease related genes
- Enzymes
- Potential drug targets
- Predicted intracellular proteins
Protein Domains for PRKN Gene
- InterPro:
- Blocks:
-
- Zn-finger, cysteine-rich C6HC
- Ubiquitin domain
- Parkin signature
- ProtoNet:
Suggested Antigen Peptide Sequences for PRKN Gene
- GenScript: Design optimal peptide antigens:
-
- Truncated parkin variant SV4DEL (D3JZW5_HUMAN)
- Parkin variant SV9DEL (D3JZW7_HUMAN)
- Parkin variant SV5,9DEL (D3K2X0_HUMAN)
- Truncated parkin variant SV3,8,9DEL (D3K2X1_HUMAN)
- Truncated parkin variant SV1bINS (D3K2X2_HUMAN)
Graphical View of Domain Structure for InterPro Entry
O60260UniProtKB/Swiss-Prot:
PRKN_HUMAN :- The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.
- Belongs to the RBR family. Parkin subfamily.
- Domain:
-
- The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.
- The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.
- 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).
- Family:
-
- Belongs to the RBR family. Parkin subfamily.
Function for PRKN Gene
Molecular function for PRKN Gene
- UniProtKB/Swiss-Prot 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, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, 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, PubMed:29311685). 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.
- UniProtKB/Swiss-Prot CatalyticActivity:
- Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.; EC=2.3.2.31; Evidence={ECO:0000269|PubMed:23770887};.
- UniProtKB/Swiss-Prot EnzymeRegulation:
- 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).
Enzyme Numbers (IUBMB) for PRKN Gene
Phenotypes From GWAS Catalog for PRKN Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000976 | transcription regulatory region sequence-specific DNA binding | IDA | 23985028 |
| GO:0001227 | DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA | 23985028 |
| GO:0001664 | G protein-coupled receptor binding | IPI | 12150907 |
| GO:0003779 | actin binding | IPI | 21753002 |
| GO:0004842 | ubiquitin-protein transferase activity | IEA,TAS | -- |
Phenotypes for PRKN Gene
- MGI mutant phenotypes for PRKN:
-
inferred from 10 alleles
- nervous system phenotype
- respiratory system phenotype
- normal phenotype
- cardiovascular system phenotype
- cellular phenotype
- behavior/neurological phenotype
- mortality/aging
- muscle phenotype
- homeostasis/metabolism phenotype
- growth/size/body region phenotype
- skeleton phenotype
- integument phenotype
- no phenotypic analysis
- GenomeRNAi human phenotypes for PRKN:
Animal Models for PRKN Gene
Animal Model Products
- Taconic Biosciences: Generate A Custom CRISPR Mouse Model For Your Study
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for PRKN - Select products 50% OFF >
- * PRKN CRISPR as ready-to-use vector or virus: ORF | Lenti- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
OriGene CRISPR knockouts for PRKN
- Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for PRKN
miRNA for PRKN Gene
- miRTarBase miRNAs that target PRKN
-
- hsa-miR-335-5p (MIRT016831)
- hsa-miR-26b-5p (MIRT028924)
- hsa-miR-3187-3p (MIRT516512)
- hsa-miR-1303 (MIRT516513)
- hsa-miR-4435 (MIRT516514)
- hsa-miR-588 (MIRT516515)
- hsa-miR-4701-5p (MIRT516516)
- hsa-miR-548s (MIRT516517)
- hsa-miR-193b-5p (MIRT516518)
- hsa-miR-4755-3p (MIRT516519)
- hsa-miR-483-5p (MIRT516520)
- hsa-miR-19a-3p (MIRT727013)
- hsa-miR-19b-3p (MIRT727014)
- hsa-miR-181a-5p (MIRT734362)
miRNA Products
Inhibitory RNA Products
- Origene shrna, sirna, and RNAi products in human, mouse, rat for PRKN
- Browse OriGene Inhibitory RNA Products For PRKN
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Clone Products
- Applied Biological Materials (abm): Clones for PRKN - Select products 50% OFF >
- * PRKN as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
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- MG227497
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- RC216186L3
- RC216186L4
- RC221147
- RC221147L1
- RC221147L2
- RC221147L3
- RC221147L4
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- RR212553
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- MR227497L1V
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- MR227497L4V
- RC216186L1V
- RC216186L2V
- RC216186L3V
- RC216186L4V
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- RC221147L3V
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- RC222635L4V
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- RR212553L4V
- Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
- Sino Biological Human cDNA Clone for PRKN
- Addgene plasmids for PRKN
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for PRKN
Cell Line Products
-
Horizon Cell Lines for PRKN
No data available for Transcription Factor Targets and HOMER Transcription for PRKN Gene
Localization for PRKN Gene
Subcellular locations from UniProtKB/Swiss-Prot for PRKN Gene
- 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.
| Compartment | Confidence |
|---|---|
| mitochondrion | 5 |
| nucleus | 5 |
| cytosol | 5 |
| golgi apparatus | 5 |
| endoplasmic reticulum | 4 |
| lysosome | 3 |
| plasma membrane | 2 |
| extracellular | 2 |
| cytoskeleton | 2 |
| peroxisome | 2 |
| endosome | 2 |
- Cytosol (3)
- Nuclear speckles (3)
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000151 | ubiquitin ligase complex | IDA | 12150907 |
| GO:0005623 | cell | IEA | -- |
| GO:0005634 | nucleus | IDA | 23985028 |
| GO:0005737 | cytoplasm | IBA,IDA | 17512523 |
| GO:0005739 | colocalizes_with mitochondrion | IEA,IMP | 21508222 |
Pathways & Interactions for PRKN Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Class I MHC mediated antigen processing and presentation | ||
| 2 | Metabolism of proteins | ||
| 3 | Mitophagy |
1.00
|
|
| 4 | Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway |
Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway
.97
|
|
| 5 | Neuroscience | ||
Pathways by source for PRKN Gene
3 BioSystems pathways for PRKN Gene
11 Reactome pathways for PRKN Gene
4 KEGG pathways for PRKN Gene
2 GeneGo (Thomson Reuters) pathways for PRKN Gene
- Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway
- Proteolysis_Putative ubiquitin pathway
1 Qiagen pathway for PRKN Gene
- Parkinson's Disease Pathway
1 Cell Signaling Technology pathway for PRKN Gene
UniProtKB/Swiss-Prot O60260-PRKN_HUMAN
- Pathway: Protein modification; protein ubiquitination.
Interacting Proteins for PRKN Gene
Selected Interacting proteins:
O60260-PRKN_HUMAN
ENSP00000355865
for PRKN Gene via
UniProtKB
MINT
STRING
IID
GPS-Prot Interaction Network for PRKN
SIGNOR curated interactions for PRKN Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000122 | negative regulation of transcription by RNA polymerase II | IMP | 23985028 |
| GO:0000209 | protein polyubiquitination | IBA,IDA | 12150907 |
| GO:0000266 | mitochondrial fission | ISS | -- |
| GO:0000422 | autophagy of mitochondrion | IMP | 19029340 |
| GO:0000423 | mitophagy | IEA | -- |
Drugs & Compounds for PRKN Gene
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| Calcium | Nutra | 6556 |
| Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
|---|
Drug Products
- Creative Biomart Recombinant Human PARK2
Transcripts for PRKN Gene
mRNA/cDNA for PRKN Gene
- 3 REFSEQ mRNAs :
- 31 NCBI additional mRNA sequence :
- 26 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :
-
- ENST00000338468 1276 nts (view in UCSC)
- ENST00000366892 1505 nts (view in UCSC)
- ENST00000366894 1157 nts (view in UCSC)
- ENST00000366896 2514 nts (view in UCSC)
- ENST00000366897 2877 nts (view in UCSC)
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for PRKN - Select products 50% OFF >
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- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
OriGene CRISPR knockouts for PRKN
- Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for PRKN
miRNA Products
Inhibitory RNA Products
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Clone Products
- Applied Biological Materials (abm): Clones for PRKN - Select products 50% OFF >
- * PRKN as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
- MG227497
- MR227497
- MR227497L1
- MR227497L2
- MR227497L3
- MR227497L4
- RC216186
- RC216186L1
- RC216186L2
- RC216186L3
- RC216186L4
- RC221147
- RC221147L1
- RC221147L2
- RC221147L3
- RC221147L4
- RC222635
- RC222635L3
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- RG216186
- RG221147
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- RR212553
- RR212553L3
- RR212553L4
- MR227497L1V
- MR227497L2V
- MR227497L3V
- MR227497L4V
- RC216186L1V
- RC216186L2V
- RC216186L3V
- RC216186L4V
- RC221147L1V
- RC221147L2V
- RC221147L3V
- RC221147L4V
- RC222635L3V
- RC222635L4V
- RR212553L3V
- RR212553L4V
- Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
- Sino Biological Human cDNA Clone for PRKN
- Addgene plasmids for PRKN
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for PRKN
Relevant External Links for PRKN Gene
- GeneLoc Exon Structure for
- PRKN
Expression for PRKN Gene
Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PRKN
mRNA Expression by UniProt/SwissProt for PRKN Gene:
O60260-PRKN_HUMAN
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).
Evidence on tissue expression from TISSUES for PRKN Gene
- Nervous system(4.8)
- Muscle(4.6)
- Eye(4.4)
- Heart(2.8)
- Kidney(2.7)
- Skin(2.5)
- Blood(2.4)
- Adrenal gland(2.4)
- Liver(2.2)
- Intestine(2.2)
- Pancreas(2.1)
Phenotype-based relationships between genes and organs from Gene ORGANizer for PRKN Gene
Germ Layers:
- ectoderm
- endoderm
- mesoderm
Systems:
- integumentary
- nervous
- reproductive
- respiratory
- skeletal muscle
- urinary
Regions:
Head and neck:
- brain
- cerebellum
- eye
- eyelid
- face
- head
Thorax:
- breast
- lung
Pelvis:
- ovary
- testicle
- urethra
- urinary bladder
General:
- peripheral nerve
- peripheral nervous system
- skin
- spinal cord
Primer Products
-
OriGene qPCR primer pairs for PRKN
No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for PRKN Gene
Orthologs for PRKN Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| Chimpanzee (Pan troglodytes) |
Mammalia | PARK2 30 31 |
|
OneToOne | |
| Platypus (Ornithorhynchus anatinus) |
Mammalia | PARK2 31 |
|
OneToOne | |
| Dog (Canis familiaris) |
Mammalia | PARK2 30 31 |
|
OneToOne | |
| Cow (Bos Taurus) |
Mammalia | PARK2 30 31 |
|
OneToOne | |
| Rat (Rattus norvegicus) |
Mammalia | Park2 30 |
|
||
| Mouse (Mus musculus) |
Mammalia | Park2 30 31 31 |
|
OneToMany | |
| Prkn 17 |
|
||||
| Oppossum (Monodelphis domestica) |
Mammalia | PARK2 31 |
|
OneToOne | |
| Chicken (Gallus gallus) |
Aves | PARK2 30 31 |
|
OneToOne | |
| Lizard (Anolis carolinensis) |
Reptilia | PARK2 31 |
|
OneToOne | |
| Zebrafish (Danio rerio) |
Actinopterygii | park2 30 31 |
|
OneToOne | |
| African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP006580 30 |
|
||
| Fruit Fly (Drosophila melanogaster) |
Insecta | park 30 31 |
|
OneToOne | |
| Worm (Caenorhabditis elegans) |
Secernentea | pdr-1 30 31 |
|
OneToOne |
- Species where no ortholog for PRKN was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Eremothecium gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African clawed frog (Xenopus laevis)
- Alicante grape (Vitis vinifera)
- Alpha proteobacteria (Wolbachia pipientis)
- Amoeba (Dictyostelium discoideum)
- Archea (Pyrococcus horikoshii)
- Baker's yeast (Saccharomyces cerevisiae)
- Barley (Hordeum vulgare)
- Beta proteobacteria (Neisseria meningitidis)
- Bread mold (Neurospora crassa)
- Chromalveolata (Phytophthora infestans)
- Common water flea (Daphnia pulex)
- Corn (Zea mays)
- E. coli (Escherichia coli)
- Filamentous fungi (Aspergillus nidulans)
- Firmicute Bacteria (Streptococcus pneumoniae)
- Fission Yeast (Schizosaccharomyces pombe)
- Green Algae (Chlamydomonas reinhardtii)
- Honey Bee (Apis mellifera)
- K. Lactis Yeast (Kluyveromyces lactis)
- Loblloly Pine (Pinus taeda)
- Malaria Parasite (Plasmodium falciparum)
- Medicago Trunc (Medicago Truncatula)
- Moss (Physcomitrella patens)
- Orangutan (Pongo pygmaeus)
- Pig (Sus scrofa)
- Rainbow Trout (Oncorhynchus mykiss)
- Rice (Oryza sativa)
- Rice Blast Fungus (Magnaporthe grisea)
- Schistosome Parasite (Schistosoma mansoni)
- Sea Anemone (Nematostella vectensis)
- Sea Vase (Ciona intestinalis)
- Sea Squirt (Ciona savignyi)
- Sea Urchin (Strongylocentrotus purpuratus)
- Sorghum (Sorghum bicolor)
- Soybean (Glycine max)
- Stem Rust Fungus (Puccinia graminis)
- Sugarcane (Saccharum officinarum)
- Thale Cress (Arabidopsis thaliana)
- Tomato (Lycopersicon esculentum)
- Toxoplasmosis (Toxoplasma gondii)
- Trichoplax (Trichoplax adhaerens)
- Tropical Clawed Frog (Silurana tropicalis)
- Wheat (Triticum aestivum)
Evolution for PRKN Gene
- ENSEMBL:
- Gene Tree for PRKN (if available)
- TreeFam:
- Gene Tree for PRKN (if available)
- Aminode:
- Evolutionary constrained regions (ECRs) for PRKN: view image
Paralogs for PRKN Gene
Variants for PRKN Gene
Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PRKN Gene
| SNP ID | Clinical significance and condition | Chr 06 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| 639788 | Uncertain Significance: not provided | 161,549,000(-) | T/C | MISSENSE_VARIANT | |
| 644125 | Pathogenic: not provided | 162,443,356(-) | C/G | MISSENSE_VARIANT | |
| 645725 | Pathogenic: Parkinson disease 2; not provided | 161,785,885(-) | C/T | MISSENSE_VARIANT | |
| 648034 | Uncertain Significance: Parkinson disease 2 | 162,262,637(-) | C/G | MISSENSE_VARIANT,INTRON_VARIANT | |
| 649511 | Uncertain Significance: Parkinson disease 2 | 161,785,844(-) | A/G | MISSENSE_VARIANT |
Residual Variation Intolerance Score:
93.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
8.08;
84.45% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for PRKN Gene
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PRKN Gene
Disorders for PRKN Gene
(69) MalaCards diseases for PRKN Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| parkinson disease 2, autosomal recessive juvenile |
|
|
| ovarian cancer |
|
|
| leprosy 2 |
|
|
| lung cancer |
|
|
| parkinson disease, late-onset |
|
Search PRKN in MalaCards
View complete list of genes associated with diseases
UniProtKB/Swiss-Prot
PRKN_HUMAN- 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. {ECO:0000269 PubMed:12629236, ECO:0000269 PubMed:12730996, ECO:0000269 PubMed:19966284, ECO:0000269 PubMed:29311685}. 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. {ECO:0000269 PubMed:10072423, ECO:0000269 PubMed:10824074, ECO:0000269 PubMed:10888878, ECO:0000269 PubMed:10939576, ECO:0000269 PubMed:11163284, ECO:0000269 PubMed:11179010, ECO:0000269 PubMed:11431533, ECO:0000269 PubMed:11487568, ECO:0000269 PubMed:11590439, ECO:0000269 PubMed:11971093, ECO:0000269 PubMed:12056932, ECO:0000269 PubMed:12112109, ECO:0000269 PubMed:12114481, ECO:0000269 PubMed:12116199, ECO:0000269 PubMed:12362318, ECO:0000269 PubMed:12397156, ECO:0000269 PubMed:12629236, ECO:0000269 PubMed:12730996, ECO:0000269 PubMed:12925569, ECO:0000269 PubMed:15584030, ECO:0000269 PubMed:17360614, ECO:0000269 PubMed:19229105, ECO:0000269 PubMed:19801972, ECO:0000269 PubMed:20404107, ECO:0000269 PubMed:20889486, ECO:0000269 PubMed:20889974, ECO:0000269 PubMed:21376232, ECO:0000269 PubMed:22956510, ECO:0000269 PubMed:9560156, ECO:0000269 PubMed:9731209}. Note=The disease is caused by mutations affecting the gene represented in this entry.
- Note=Defects in PRKN may be involved in the development and/or progression of ovarian cancer.
Additional Disease Information for PRKN
No data available for Genatlas for PRKN Gene
Publications for PRKN Gene
- PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. (PMID: 20404107) Matsuda N … Tanaka K (The Journal of cell biology 2010) 3 4 23
- PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. (PMID: 19966284) Vives-Bauza C … Przedborski S (Proceedings of the National Academy of Sciences of the United States of America 2010) 3 4 23
- Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. (PMID: 19229105) Xiong H … Zhang Z (The Journal of clinical investigation 2009) 3 4 23
- Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. (PMID: 19801972) da Costa CA … Checler F (Nature cell biology 2009) 3 4 23
- Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. (PMID: 17846173) Olzmann JA … Chin LS (The Journal of cell biology 2007) 3 4 23
ExternalLinks
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