PARK2 ELISA Kit (Human) (OKCD00600)

E3 ubiquitin-protein ligase parkin

5071

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, SEPT5, 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). 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.28 Publications < p>Manually curated information for which there is published experimental evidence.< /p> < p>< a href="/manual/evidences#ECO:0000269">Moreâa‚¬A< /a>< /p> Manual assertion based on experiment iniRef.11"Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity."_x005F_x000D_ Imai Y., Soda M., Takahashi R._x005F_x000D_ J. Biol. Chem. 275:35661-35664(2000) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN UBIQUITINATION.Ref.12"Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase."_x005F_x000D_ Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T._x005F_x000D_ Nat. Genet. 25:302-305(2000) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240.Ref.15"Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease."_x005F_x000D_ Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A., Dawson V.L., Dawson T.M._x005F_x000D_ Nat. Med. 7:1144-1150(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK2 ARG-240; CYS-256; TRP-275 AND ASN-415, MUTAGENESIS OF CYS-337; CYS-421 AND CYS-431.Ref.16"Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease."_x005F_x000D_ Shimura H., Schlossmacher M.G., Hattori N., Frosch M.P., Trockenbacher A., Schneider R., Mizuno Y., Kosik K.S., Selkoe D.J._x005F_x000D_ Science 293:263-269(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240.Ref.21"Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity."_x005F_x000D_ Staropoli J.F., McDermott C., Martinat C., Schulman B., Demireva E., Abeliovich A._x005F_x000D_ Neuron 37:735-749(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH FBXW7 AND CUL1, UBIQUITINATION OF CYCLIN E.Ref.23"Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27."_x005F_x000D_ Cesari R., Martin E.S., Calin G.A., Pentimalli F., Bichi R., McAdams H., Trapasso F., Drusco A., Shimizu M., Masciullo V., D'Andrilli G., Scambia G., Picchio M.C., Alder H., Godwin A.K., Croce C.M._x005F_x000D_ Proc. Natl. Acad. Sci. U.S.A. 100:5956-5961(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INVOLVEMENT IN CANCER.Ref.25"S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function."_x005F_x000D_ Chung K.K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L., Dawson V.L., Dawson T.M._x005F_x000D_ Science 304:1328-1331(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, UBIQUITINATION, S-NITROSYLATION.Ref.27"Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation."_x005F_x000D_ Lim K.L., Chew K.C., Tan J.M., Wang C., Chung K.K., Zhang Y., Tanaka Y., Smith W., Engelender S., Ross C.A., Dawson V.L., Dawson T.M._x005F_x000D_ J. Neurosci. 25:2002-2009(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH SNCAIP.Ref.28"Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death."_x005F_x000D_ Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K.K., Pletnikova O., Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.-J., Kim M.J., Kim S., Dawson V.L., Dawson T.M._x005F_x000D_ J. Neurosci. 25:7968-7978(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH AIMP2.Ref.32"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6."_x005F_x000D_ Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S._x005F_x000D_ J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION.Ref.33"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy."_x005F_x000D_ Narendra D., Tanaka A., Suen D.F., Youle R.J._x005F_x000D_ J. Cell Biol. 183:795-803(2008) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION.Ref.34"Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress."_x005F_x000D_ Yu F., Zhou J._x005F_x000D_ Neurosci. Lett. 440:4-8(2008) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH RNF41, UBIQUITINATION, MUTAGENESIS OF CYS-421, FUNCTION.Ref.35"Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation."_x005F_x000D_ Xiong H., Wang D., Chen L., Choo Y.S., Ma H., Tang C., Xia K., Jiang W., Ronai Z., Zhuang X., Zhang Z._x005F_x000D_ J. Clin. Invest. 119:650-660(2009) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, COMPONENT OF A COMPLEX COMPOSED OF PARK2; PARK7 AND PINK1, SUBCELLULAR LOCATION, UBIQUITINATION, CHARACTERIZATION OF VARIANT PARK2 PRO-42.Ref.36"Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease."_x005F_x000D_ da Costa C.A., Sunyach C., Giaime E., West A., Corti O., Brice A., Safe S., Abou-Sleiman P.M., Wood N.W., Takahashi H., Goldberg M.S., Shen J., Checler F._x005F_x000D_ Nat. Cell Biol. 11:1370-1375(2009) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN PROTECTION OF APOPTOSIS, CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441, DOMAIN.Ref.38"Parkin mono-ubiquitinates Bcl-2 and regulates autophagy."_x005F_x000D_ Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G._x005F_x000D_ J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH BCL2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437.Ref.39"PINK1-dependent recruitment of Parkin to mitochondria in mitophagy."_x005F_x000D_ Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., Tocilescu M.A., Liu W., Ko H.S., Magrane J., Moore D.J., Dawson V.L., Grailhe R., Dawson T.M., Li C., Tieu K., Przedborski S._x005F_x000D_ Proc. Natl. Acad. Sci. U.S.A. 107:378-383(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH PINK1, CHARACTERIZATION OF VARIANTS PARK ASN-415 AND ASP-430.Ref.40"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease."_x005F_x000D_ Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O., Troconso J.C., Dawson V.L., Dawson T.M._x005F_x000D_ Cell 144:689-702(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH ZNF746, CHARACTERIZATION OF VARIANTS PARK2 TRP-275; ASP-430 AND PHE-431.Ref.41"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids."_x005F_x000D_ Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E._x005F_x000D_ Nature 474:105-108(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, REACTION MECHANISM, INTERACTION WITH UBE2L3.Ref.42"Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential."_x005F_x000D_ Kuroda Y., Sako W., Goto S., Sawada T., Uchida D., Izumi Y., Takahashi T., Kagawa N., Matsumoto M., Matsumoto M., Takahashi R., Kaji R., Mitsui T._x005F_x000D_ Hum. Mol. Genet. 21:991-1003(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CHPF, SUBCELLULAR LOCATION.Ref.43"Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation."_x005F_x000D_ Iguchi M., Kujuro Y., Okatsu K., Koyano F., Kosako H., Kimura M., Suzuki N., Uchiyama S., Tanaka K., Matsuda N._x005F_x000D_ J. Biol. Chem. 288:22019-22032(2013) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-65, FUNCTION, SUBCELLULAR LOCATION.Ref.44"The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy."_x005F_x000D_ Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., Plun-Favreau H._x005F_x000D_ Nat. Neurosci. 16:1257-1265(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXO7.Ref.46"PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria."_x005F_x000D_ Chen Y., Dorn G.W. II_x005F_x000D_ Science 340:471-475(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN MITOPHAGY, INTERACTION WITH MFN2, SUBCELLULAR LOCATION.Ref.47"Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65."_x005F_x000D_ Kazlauskaite A., Kondapalli C., Gourlay R., Campbell D.G., Ritorto M.S., Hofmann K., Alessi D.R., Knebel A., Trost M., Muqit M.M._x005F_x000D_ Biochem. J. 460:127-139(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-65, UBIQUITIN-BINDING, ENZYME REGULATION, MUTAGENESIS OF SER-65.Ref.48"PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity."_x005F_x000D_ Kane L.A., Lazarou M., Fogel A.I., Li Y., Yamano K., Sarraf S.A., Banerjee S., Youle R.J._x005F_x000D_ J. Cell Biol. 205:143-153(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, ENZYME REGULATION.Ref.49"Ubiquitin is phosphorylated by PINK1 to activate parkin."_x005F_x000D_ Koyano F., Okatsu K., Kosako H., Tamura Y., Go E., Kimura M., Kimura Y., Tsuchiya H., Yoshihara H., Hirokawa T., Endo T., Fon E.A., Trempe J.F., Saeki Y., Tanaka K., Matsuda N._x005F_x000D_ Nature 510:162-166(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-65, UBIQUITIN-BINDING, ENZYME REGULATION, MUTAGENESIS OF SER-65 AND TRP-403.Ref.50"The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy."_x005F_x000D_ Bingol B., Tea J.S., Phu L., Reichelt M., Bakalarski C.E., Song Q., Foreman O., Kirkpatrick D.S., Sheng M._x005F_x000D_ Nature 510:370-375(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION.Ref.51"Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis."_x005F_x000D_ Wauer T., Swatek K.N., Wagstaff J.L., Gladkova C., Pruneda J.N., Michel M.A., Gersch M., Johnson C.M., Freund S.M., Komander D._x005F_x000D_ EMBO J. 34:307-325(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, ENZYME REGULATION.Ref.52"USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria."_x005F_x000D_ Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M., Kirkpatrick D.S., Bingol B., Corn J.E._x005F_x000D_ Nat. Cell Biol. 17:160-169(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION.

< 0.053 ng/mL