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PARK2

Reviewed July 2007

What is the official name of the PARK2 gene?

The official name of this gene is “parkinson protein 2, E3 ubiquitin protein ligase (parkin).”

PARK2 is the gene's official symbol. The PARK2 gene is also known by other names, listed below.

What is the normal function of the PARK2 gene?

The PARK2 gene, one of the largest human genes, provides instructions for making a protein called parkin. Parkin plays a role in the cell machinery that breaks down (degrades) unwanted proteins by tagging damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to move unwanted proteins into specialized cell structures known as proteasomes, where the proteins are degraded. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. Because of its activity in the ubiquitin-proteasome system, parkin belongs to a protein group called E3 protein-ubiquitin ligases.

Studies of the structure and activity of parkin have led researchers to suggest other activities for this protein. Parkin may act as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. Parkin may also regulate the supply and release of sacs, called synaptic vesicles, from nerve cells. Synaptic vesicles contain chemical messengers that transmit signals from one nerve cell to another.

How are changes in the PARK2 gene related to health conditions?

Parkinson disease - caused by mutations in the PARK2 gene

Researchers have identified more than 100 PARK2 mutations that cause juvenile Parkinson disease and some adult-onset cases. Some mutations lead to an abnormally small parkin protein, which is nonfunctional and degrades rapidly. Other mutations change the building blocks (amino acids) used to make parkin, and the altered protein cannot function properly. PARK2 mutations usually lead to a loss of parkin activity.

It is not clearly understood how PARK2 mutations cause Parkinson disease. The loss of parkin activity probably disturbs the ubiquitin-proteasome system, which allows unwanted proteins to accumulate. Accumulated proteins could disrupt normal cell activities such as the supply and release of synaptic vesicles, particularly those that contain a chemical messenger called dopamine. As parkin is normally abundant in the brain, its loss could lead to the impairment or death of nerve cells, including those that produce dopamine. Loss of dopamine-producing nerve cells is a characteristic feature of Parkinson disease.

cancers - associated with the PARK2 gene

The PARK2 gene spans part of a fragile area (known as FRA6E) on chromosome 6. This fragile area is unstable and prone to breakage and rearrangement. In tumors from some patients with ovarian or lung cancer, segments of the PARK2 gene within the FRA6E region are deleted or duplicated. As a result of these alterations, parkin activity is absent or reduced. These findings suggest that the PARK2 gene normally acts as a tumor suppressor gene, by restraining cell division and growth. If it is altered, cells can grow and divide in an uncontrolled manner, leading to a tumor.

other disorders - increased risk from variations of the PARK2 gene

Recent studies suggest that normal variations (polymorphisms) in the PARK2 gene (and a neighboring gene called PACRG) can increase the risk of contracting leprosy. Leprosy is a disease that affects the nerves and skin and is caused by the bacterium Mycobacterium leprae. It remains unclear how PARK2 polymorphisms increase leprosy susceptibility. Researchers believe that the ubiquitin-proteasome system may play a role in controlling infection. PARK2 polymorphisms may slightly alter parkin's function, making the ubiquitin-proteasome system less efficient.

Where is the PARK2 gene located?

Cytogenetic Location: 6q25.2-q27

Molecular Location on chromosome 6: base pairs 161,768,589 to 163,148,833

The PARK2 gene is located on the long (q) arm of chromosome 6 between positions 25.2 and 27.

The PARK2 gene is located on the long (q) arm of chromosome 6 between positions 25.2 and 27.

More precisely, the PARK2 gene is located from base pair 161,768,589 to base pair 163,148,833 on chromosome 6.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PARK2?

You and your healthcare professional may find the following resources about PARK2 helpful.

  • Educational resources - Information pages

    • Annual Reviews Collection: Overview of the Ubiquitin-Proteasome Degradation System (http://www.ncbi.nlm.nih.gov/books/NBK2229/)
    • Biochemistry (fifth edition, 2002): Protein Turnover is Tightly Regulated (http://www.ncbi.nlm.nih.gov/books/NBK22397/)
    • National Institute of Allergy and Infectious Diseases: Leprosy (Hansen's Disease) (http://www.niaid.nih.gov/topics/leprosy/understanding/pages/whatis.aspx)
    • The Cell: A Molecular Approach (second edition, 2000): The Ubiquitin-Proteasome Pathway (http://www.ncbi.nlm.nih.gov/books/NBK9957/)

  • Gene Reviews - Clinical summary

    • Gene Review: Parkinson Disease (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=parkinson-overview)
    • Gene Review: Parkin Type of Juvenile Parkinson Disease (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=jpd)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/54102)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((PARK2%5BTIAB%5D)%20OR%20(parkin%20AND%20protein%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_PARK2.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5071)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=5071)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=8607)
    • Parkinson Disease Mutation Database (http://www.molgen.ua.ac.be/PDmutDB/default.cfm?MT=1&ML=1&Page=MutByQuery&Query=tblContexts.GeneSymbol%20In%20%28%27PARK2%27%29&Selection=Gene%20In%20%28PARK2%29)

What other names do people use for the PARK2 gene or gene products?

  • AR-JP
  • parkin
  • Parkinson disease (autosomal recessive, juvenile) 2, parkin
  • PDJ
  • PRKN
  • PRKN2_HUMAN
  • ubiquitin E3 ligase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PARK2?

acids ; amino acid ; autosomal ; autosomal recessive ; bacteria ; cancer ; cell ; cell division ; chromosome ; dopamine ; gene ; infection ; juvenile ; ligase ; molecule ; mutation ; mycobacteria ; nerve cell ; ovarian ; polymorphism ; proteasome ; protein ; rearrangement ; recessive ; susceptibility ; synaptic vesicles ; tumor ; tumor suppressor gene ; ubiquitin ; vesicle

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16495942?dopt=Abstract)
  • Dawson TM, Dawson VL. The role of parkin in familial and sporadic Parkinson's disease. Mov Disord. 2010;25 Suppl 1:S32-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20187240?dopt=Abstract)
  • Denison SR, Callahan G, Becker NA, Phillips LA, Smith DI. Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer. 2003 Sep;38(1):40-52. (http://www.ncbi.nlm.nih.gov/pubmed/12874785?dopt=Abstract)
  • Denison SR, Wang F, Becker NA, Schüle B, Kock N, Phillips LA, Klein C, Smith DI. Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene. 2003 Nov 13;22(51):8370-8. (http://www.ncbi.nlm.nih.gov/pubmed/14614460?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5071)
  • Kay DM, Stevens CF, Hamza TH, Montimurro JS, Zabetian CP, Factor SA, Samii A, Griffith A, Roberts JW, Molho ES, Higgins DS, Gancher S, Moses L, Zareparsi S, Poorkaj P, Bird T, Nutt J, Schellenberg GD, Payami H. A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2. Neurology. 2010 Sep 28;75(13):1189-94. (http://www.ncbi.nlm.nih.gov/pubmed/20876472?dopt=Abstract)
  • Mira MT, Alcaïs A, Nguyen VT, Moraes MO, Di Flumeri C, Vu HT, Mai CP, Nguyen TH, Nguyen NB, Pham XK, Sarno EN, Alter A, Montpetit A, Moraes ME, Moraes JR, Doré C, Gallant CJ, Lepage P, Verner A, Van De Vosse E, Hudson TJ, Abel L, Schurr E. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature. 2004 Feb 12;427(6975):636-40. Epub 2004 Jan 25. (http://www.ncbi.nlm.nih.gov/pubmed/14737177?dopt=Abstract)
  • Narendra DP, Youle RJ. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal. 2011 May 15;14(10):1929-38. Epub 2011 Mar 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21194381?dopt=Abstract)
  • Picchio MC, Martin ES, Cesari R, Calin GA, Yendamuri S, Kuroki T, Pentimalli F, Sarti M, Yoder K, Kaiser LR, Fishel R, Croce CM. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004 Apr 15;10(8):2720-4. (http://www.ncbi.nlm.nih.gov/pubmed/15102676?dopt=Abstract)
  • Pramstaller PP, Schlossmacher MG, Jacques TS, Scaravilli F, Eskelson C, Pepivani I, Hedrich K, Adel S, Gonzales-McNeal M, Hilker R, Kramer PL, Klein C. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol. 2005 Sep;58(3):411-22. (http://www.ncbi.nlm.nih.gov/pubmed/16130111?dopt=Abstract)
  • Schurr E, Alcaïs A, de Léséleuc L, Abel L. Genetic predisposition to leprosy: A major gene reveals novel pathways of immunity to Mycobacterium leprae. Semin Immunol. 2006 Dec;18(6):404-10. Epub 2006 Sep 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16973374?dopt=Abstract)
  • Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000 Jul;25(3):302-5. (http://www.ncbi.nlm.nih.gov/pubmed/10888878?dopt=Abstract)
  • Veeriah S, Taylor BS, Meng S, Fang F, Yilmaz E, Vivanco I, Janakiraman M, Schultz N, Hanrahan AJ, Pao W, Ladanyi M, Sander C, Heguy A, Holland EC, Paty PB, Mischel PS, Liau L, Cloughesy TF, Mellinghoff IK, Solit DB, Chan TA. Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2010 Jan;42(1):77-82. Epub 2009 Nov 29. (http://www.ncbi.nlm.nih.gov/pubmed/19946270?dopt=Abstract)
  • von Coelln R, Dawson VL, Dawson TM. Parkin-associated Parkinson's disease. Cell Tissue Res. 2004 Oct;318(1):175-84. Epub 2004 Jul 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15503153?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2007
Published: May 21, 2012