| Structural highlights
5n38 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | , |
| Gene: | PARK2, PRKN (HUMAN), UBB (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[PRKN2_HUMAN] Defects in PARK2 are a cause of 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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] Defects in PARK2 are the cause of Parkinson disease type 2 (PARK2) [MIM:600116]; also known as early-onset parkinsonism with diurnal fluctuation (EPDF) or autosomal recessive juvenile Parkinson disease (PDJ). A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually befor 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.[26] [27] [28] [29] [30] [31] [32] [33] [34] [35] Note=Defects in PARK2 may be involved in the development and/or progression of ovarian cancer.
Function
[PRKN2_HUMAN] 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. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. 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. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene.[36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [UBB_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[50] [51]
Publication Abstract from PubMed
RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.
Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.,Kumar A, Chaugule VK, Condos TEC, Barber KR, Johnson C, Toth R, Sundaramoorthy R, Knebel A, Shaw GS, Walden H Nat Struct Mol Biol. 2017 Apr 17. doi: 10.1038/nsmb.3400. PMID:28414322[52]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. PMID:10888878 doi:10.1038/77060
- ↑ Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G. Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem. 2010 Dec 3;285(49):38214-23. doi: 10.1074/jbc.M110.101469. Epub 2010, Oct 2. PMID:20889974 doi:10.1074/jbc.M110.101469
- ↑ Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378-83. doi: 10.1073/pnas.0911187107., Epub 2009 Dec 4. PMID:19966284 doi:10.1073/pnas.0911187107
- ↑ Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM. PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease. Cell. 2011 Mar 4;144(5):689-702. doi: 10.1016/j.cell.2011.02.010. PMID:21376232 doi:10.1016/j.cell.2011.02.010
- ↑ Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001 Oct;7(10):1144-50. PMID:11590439 doi:10.1038/nm1001-1144
- ↑ Huynh DP, Scoles DR, Nguyen D, Pulst SM. The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum Mol Genet. 2003 Oct 15;12(20):2587-97. Epub 2003 Aug 12. PMID:12925569 doi:http://dx.doi.org/10.1093/hmg/ddg269
- ↑ Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001 Jul 13;293(5528):263-9. Epub 2001 Jun 28. PMID:11431533 doi:10.1126/science.1060627
- ↑ Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605-8. PMID:9560156 doi:10.1038/33416
- ↑ Beasley SA, Hristova VA, Shaw GS. Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3095-100. PMID:17360614 doi:104/9/3095
- ↑ Hattori N, Matsumine H, Asakawa S, Kitada T, Yoshino H, Elibol B, Brookes AJ, Yamamura Y, Kobayashi T, Wang M, Yoritaka A, Minoshima S, Shimizu N, Mizuno Y. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun. 1998 Aug 28;249(3):754-8. PMID:9731209
- ↑ Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Hum Mol Genet. 1999 Apr;8(4):567-74. PMID:10072423
- ↑ Maruyama M, Ikeuchi T, Saito M, Ishikawa A, Yuasa T, Tanaka H, Hayashi S, Wakabayashi K, Takahashi H, Tsuji S. Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism. Ann Neurol. 2000 Aug;48(2):245-50. PMID:10939576
- ↑ Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med. 2000 May 25;342(21):1560-7. PMID:10824074
- ↑ Periquet M, Lucking C, Vaughan J, Bonifati V, Durr A, De Michele G, Horstink M, Farrer M, Illarioshkin SN, Pollak P, Borg M, Brefel-Courbon C, Denefle P, Meco G, Gasser T, Breteler MM, Wood N, Agid Y, Brice A. Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects. Am J Hum Genet. 2001 Mar;68(3):617-26. Epub 2001 Feb 14. PMID:11179010
- ↑ Hedrich K, Kann M, Lanthaler AJ, Dalski A, Eskelson C, Landt O, Schwinger E, Vieregge P, Lang AE, Breakefield XO, Ozelius LJ, Pramstaller PP, Klein C. The importance of gene dosage studies: mutational analysis of the parkin gene in early-onset parkinsonism. Hum Mol Genet. 2001 Aug 1;10(16):1649-56. PMID:11487568
- ↑ Pineda-Trujillo N, Carvajal-Carmona LG, Buritica O, Moreno S, Uribe C, Pineda D, Toro M, Garcia F, Arias W, Bedoya G, Lopera F, Ruiz-Linares A. A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile Parkinsonism in a population from North West Colombia. Neurosci Lett. 2001 Feb 2;298(2):87-90. PMID:11163284
- ↑ West A, Periquet M, Lincoln S, Lucking CB, Nicholl D, Bonifati V, Rawal N, Gasser T, Lohmann E, Deleuze JF, Maraganore D, Levey A, Wood N, Durr A, Hardy J, Brice A, Farrer M. Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet. 2002 Jul 8;114(5):584-91. PMID:12116199 doi:10.1002/ajmg.10525
- ↑ Kann M, Jacobs H, Mohrmann K, Schumacher K, Hedrich K, Garrels J, Wiegers K, Schwinger E, Pramstaller PP, Breakefield XO, Ozelius LJ, Vieregge P, Klein C. Role of parkin mutations in 111 community-based patients with early-onset parkinsonism. Ann Neurol. 2002 May;51(5):621-5. PMID:12112109 doi:10.1002/ana.10179
- ↑ Nichols WC, Pankratz N, Uniacke SK, Pauciulo MW, Halter C, Rudolph A, Conneally PM, Foroud T. Linkage stratification and mutation analysis at the Parkin locus identifies mutation positive Parkinson's disease families. J Med Genet. 2002 Jul;39(7):489-92. PMID:12114481
- ↑ Munoz E, Tolosa E, Pastor P, Marti MJ, Valldeoriola F, Campdelacreu J, Oliva R. Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism. J Neurol Neurosurg Psychiatry. 2002 Nov;73(5):582-4. PMID:12397156
- ↑ Hedrich K, Marder K, Harris J, Kann M, Lynch T, Meija-Santana H, Pramstaller PP, Schwinger E, Bressman SB, Fahn S, Klein C. Evaluation of 50 probands with early-onset Parkinson's disease for Parkin mutations. Neurology. 2002 Apr 23;58(8):1239-46. PMID:11971093
- ↑ Xu Y, Liu Z, Wang Y, Tao E, Chen G, Chen B. [A new point mutation on exon 2 of parkin gene in Parkinson's disease]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2002 Oct;19(5):409-11. PMID:12362318
- ↑ Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW, Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP, Middleton LT, Haines JL, Pericak-Vance MA, Vance JM. Parkin mutations and susceptibility alleles in late-onset Parkinson's disease. Ann Neurol. 2003 May;53(5):624-9. PMID:12730996 doi:10.1002/ana.10524
- ↑ Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC. Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology. 2003 Mar 11;60(5):796-801. PMID:12629236
- ↑ Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010 Apr 19;189(2):211-21. doi: 10.1083/jcb.200910140. PMID:20404107 doi:10.1083/jcb.200910140
- ↑ Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G. Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem. 2010 Dec 3;285(49):38214-23. doi: 10.1074/jbc.M110.101469. Epub 2010, Oct 2. PMID:20889974 doi:10.1074/jbc.M110.101469
- ↑ Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001 Oct;7(10):1144-50. PMID:11590439 doi:10.1038/nm1001-1144
- ↑ Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605-8. PMID:9560156 doi:10.1038/33416
- ↑ Beasley SA, Hristova VA, Shaw GS. Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3095-100. PMID:17360614 doi:104/9/3095
- ↑ Hattori N, Matsumine H, Asakawa S, Kitada T, Yoshino H, Elibol B, Brookes AJ, Yamamura Y, Kobayashi T, Wang M, Yoritaka A, Minoshima S, Shimizu N, Mizuno Y. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun. 1998 Aug 28;249(3):754-8. PMID:9731209
- ↑ Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Hum Mol Genet. 1999 Apr;8(4):567-74. PMID:10072423
- ↑ Maruyama M, Ikeuchi T, Saito M, Ishikawa A, Yuasa T, Tanaka H, Hayashi S, Wakabayashi K, Takahashi H, Tsuji S. Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism. Ann Neurol. 2000 Aug;48(2):245-50. PMID:10939576
- ↑ Hedrich K, Kann M, Lanthaler AJ, Dalski A, Eskelson C, Landt O, Schwinger E, Vieregge P, Lang AE, Breakefield XO, Ozelius LJ, Pramstaller PP, Klein C. The importance of gene dosage studies: mutational analysis of the parkin gene in early-onset parkinsonism. Hum Mol Genet. 2001 Aug 1;10(16):1649-56. PMID:11487568
- ↑ Pineda-Trujillo N, Carvajal-Carmona LG, Buritica O, Moreno S, Uribe C, Pineda D, Toro M, Garcia F, Arias W, Bedoya G, Lopera F, Ruiz-Linares A. A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile Parkinsonism in a population from North West Colombia. Neurosci Lett. 2001 Feb 2;298(2):87-90. PMID:11163284
- ↑ Kann M, Jacobs H, Mohrmann K, Schumacher K, Hedrich K, Garrels J, Wiegers K, Schwinger E, Pramstaller PP, Breakefield XO, Ozelius LJ, Vieregge P, Klein C. Role of parkin mutations in 111 community-based patients with early-onset parkinsonism. Ann Neurol. 2002 May;51(5):621-5. PMID:12112109 doi:10.1002/ana.10179
- ↑ Imai Y, Soda M, Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem. 2000 Nov 17;275(46):35661-4. PMID:10973942 doi:10.1074/jbc.C000447200
- ↑ 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. PMID:10888878 doi:10.1038/77060
- ↑ Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron. 2003 Mar 6;37(5):735-49. PMID:12628165
- ↑ Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, Trapasso F, Drusco A, Shimizu M, Masciullo V, D'Andrilli G, Scambia G, Picchio MC, Alder H, Godwin AK, Croce CM. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5956-61. Epub 2003 Apr 28. PMID:12719539 doi:10.1073/pnas.0931262100
- ↑ Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, Dawson TM. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science. 2004 May 28;304(5675):1328-31. Epub 2004 Apr 22. PMID:15105460 doi:10.1126/science.1093891
- ↑ Lim KL, Chew KC, Tan JM, Wang C, Chung KK, Zhang Y, Tanaka Y, Smith W, Engelender S, Ross CA, Dawson VL, Dawson TM. Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci. 2005 Feb 23;25(8):2002-9. PMID:15728840 doi:10.1523/JNEUROSCI.4474-04.2005
- ↑ Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, Troncoso J, Johnson B, Saffary R, Goh EL, Song H, Park BJ, Kim MJ, Kim S, Dawson VL, Dawson TM. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci. 2005 Aug 31;25(35):7968-78. PMID:16135753 doi:25/35/7968
- ↑ Olzmann JA, Li L, Chudaev MV, Chen J, Perez FA, Palmiter RD, Chin LS. Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J Cell Biol. 2007 Sep 10;178(6):1025-38. PMID:17846173 doi:10.1083/jcb.200611128
- ↑ Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008 Dec 1;183(5):795-803. doi: 10.1083/jcb.200809125. Epub 2008 Nov, 24. PMID:19029340 doi:10.1083/jcb.200809125
- ↑ Yu F, Zhou J. Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress. Neurosci Lett. 2008 Jul 25;440(1):4-8. doi: 10.1016/j.neulet.2008.05.052. Epub, 2008 May 18. PMID:18541373 doi:10.1016/j.neulet.2008.05.052
- ↑ Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G. Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem. 2010 Dec 3;285(49):38214-23. doi: 10.1074/jbc.M110.101469. Epub 2010, Oct 2. PMID:20889974 doi:10.1074/jbc.M110.101469
- ↑ Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378-83. doi: 10.1073/pnas.0911187107., Epub 2009 Dec 4. PMID:19966284 doi:10.1073/pnas.0911187107
- ↑ Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM. PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease. Cell. 2011 Mar 4;144(5):689-702. doi: 10.1016/j.cell.2011.02.010. PMID:21376232 doi:10.1016/j.cell.2011.02.010
- ↑ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011 Jun 2;474(7349):105-8. doi: 10.1038/nature09966. Epub 2011 May 1. PMID:21532592 doi:10.1038/nature09966
- ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
- ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
- ↑ Kumar A, Chaugule VK, Condos TEC, Barber KR, Johnson C, Toth R, Sundaramoorthy R, Knebel A, Shaw GS, Walden H. Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity. Nat Struct Mol Biol. 2017 Apr 17. doi: 10.1038/nsmb.3400. PMID:28414322 doi:http://dx.doi.org/10.1038/nsmb.3400
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