ID PRKN_MOUSE Reviewed; 464 AA. AC Q9WVS6; Q2KHJ9; Q9ES22; Q9ES23; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=E3 ubiquitin-protein ligase parkin {ECO:0000305}; DE EC=2.3.2.31 {ECO:0000250|UniProtKB:O60260}; DE AltName: Full=Parkin RBR E3 ubiquitin-protein ligase {ECO:0000250|UniProtKB:O60260}; GN Name=Prkn {ECO:0000250|UniProtKB:O60260}; GN Synonyms=Park2 {ECO:0000312|MGI:MGI:1355296}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RC TISSUE=Skeletal muscle; RX PubMed=10818204; DOI=10.1007/s003350010080; RA Kitada T., Asakawa S., Minoshima S., Mizuno Y., Shimizu N.; RT "Molecular cloning, gene expression, and identification of a splicing RT variant of the mouse parkin gene."; RL Mamm. Genome 11:417-421(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RC STRAIN=BALB/cJ; TISSUE=Kidney; RX PubMed=11122330; DOI=10.1111/j.1460-9568.2000.01314.x; RA Stichel C.C., Augustin M., Kuehn K., Zhu X.-R., Engels P., Ullmer C., RA Luebbert H.; RT "Parkin expression in the adult mouse brain."; RL Eur. J. Neurosci. 12:4181-4194(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=11675120; DOI=10.1016/s0165-3806(01)00234-6; RA Huynh D.P., Dy M., Nguyen D., Kiehl T.-R., Pulst S.M.; RT "Differential expression and tissue distribution of parkin isoforms during RT mouse development."; RL Brain Res. Dev. Brain Res. 130:173-181(2001). RN [5] RP FUNCTION IN UBIQUITINATION, AND S-NITROSYLATION. RX PubMed=15105460; DOI=10.1126/science.1093891; RA Chung K.K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L., RA Dawson V.L., Dawson T.M.; RT "S-nitrosylation of parkin regulates ubiquitination and compromises RT parkin's protective function."; RL Science 304:1328-1331(2004). RN [6] RP FUNCTION IN APOPTOSIS, AND DISRUPTION PHENOTYPE. RX PubMed=19801972; DOI=10.1038/ncb1981; RA da Costa C.A., Sunyach C., Giaime E., West A., Corti O., Brice A., Safe S., RA Abou-Sleiman P.M., Wood N.W., Takahashi H., Goldberg M.S., Shen J., RA Checler F.; RT "Transcriptional repression of p53 by parkin and impairment by mutations RT associated with autosomal recessive juvenile Parkinson's disease."; RL Nat. Cell Biol. 11:1370-1375(2009). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-80, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Kidney, and Liver; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP FUNCTION, AND INTERACTION WITH AMBRA1. RX PubMed=21753002; DOI=10.1523/jneurosci.1917-11.2011; RA Van Humbeeck C., Cornelissen T., Hofkens H., Mandemakers W., Gevaert K., RA De Strooper B., Vandenberghe W.; RT "Parkin interacts with Ambra1 to induce mitophagy."; RL J. Neurosci. 31:10249-10261(2011). RN [9] RP FUNCTION, INTERACTION WITH CHPF, AND DISRUPTION PHENOTYPE. RX PubMed=22082830; DOI=10.1093/hmg/ddr530; RA Kuroda Y., Sako W., Goto S., Sawada T., Uchida D., Izumi Y., Takahashi T., RA Kagawa N., Matsumoto M., Matsumoto M., Takahashi R., Kaji R., Mitsui T.; RT "Parkin interacts with Klokin1 for mitochondrial import and maintenance of RT membrane potential."; RL Hum. Mol. Genet. 21:991-1003(2012). RN [10] RP FUNCTION. RX PubMed=24192653; DOI=10.1161/circresaha.114.302734; RA Bhandari P., Song M., Chen Y., Burelle Y., Dorn G.W. II; RT "Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts RT and its containment by suppressing mitofusin."; RL Circ. Res. 114:257-265(2014). RN [11] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=24898855; DOI=10.7554/elife.01958; RA Yun J., Puri R., Yang H., Lizzio M.A., Wu C., Sheng Z.H., Guo M.; RT "MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin RT and compensates for loss of PINK1/parkin."; RL Elife 3:E01958-E01958(2014). RN [12] RP FUNCTION. RX PubMed=25474007; DOI=10.1371/journal.pgen.1004861; RA Shiba-Fukushima K., Arano T., Matsumoto G., Inoshita T., Yoshida S., RA Ishihama Y., Ryu K.Y., Nukina N., Hattori N., Imai Y.; RT "Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin RT mitochondrial tethering."; RL PLoS Genet. 10:e1004861-e1004861(2014). RN [13] RP FUNCTION. RX PubMed=29311685; DOI=10.1038/s41467-017-02593-y; RA Wang C., Kang X., Zhou L., Chai Z., Wu Q., Huang R., Xu H., Hu M., Sun X., RA Sun S., Li J., Jiao R., Zuo P., Zheng L., Yue Z., Zhou Z.; RT "Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and RT Parkinson's disease-like pathology."; RL Nat. Commun. 9:81-81(2018). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=32047033; DOI=10.1073/pnas.1909814117; RA Ham S.J., Lee D., Yoo H., Jun K., Shin H., Chung J.; RT "Decision between mitophagy and apoptosis by Parkin via VDAC1 RT ubiquitination."; RL Proc. Natl. Acad. Sci. U.S.A. 117:4281-4291(2020). RN [15] RP STRUCTURE BY NMR OF 1-76. RX PubMed=12652124; DOI=10.1023/a:1022254432039; RA Tashiro M., Okubo S., Shimotakahara S., Hatanaka H., Yasuda H., RA Kainosho M., Yokoyama S., Shindo H.; RT "NMR structure of ubiquitin-like domain in PARKIN: gene product of familial RT Parkinson's disease."; RL J. Biomol. NMR 25:153-156(2003). CC -!- FUNCTION: Functions within a multiprotein E3 ubiquitin ligase complex, CC catalyzing the covalent attachment of ubiquitin moieties onto substrate CC proteins (PubMed:32047033, PubMed:29311685). Substrates include SYT11 CC and VDAC1 (PubMed:32047033, PubMed:29311685). Other substrates are CC BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, CC TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (By similarity). Mediates CC monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and CC 'Lys-63'-linked polyubiquitination of substrates depending on the CC context (PubMed:32047033, PubMed:25474007). Participates in the removal CC and/or detoxification of abnormally folded or damaged protein by CC mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such CC as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then CC recognized by HDAC6, leading to their recruitment to aggresomes, CC followed by degradation (By similarity). Mediates 'Lys-63'-linked CC polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, CC possibly playing a role in Lewy-body formation (By similarity). CC Mediates monoubiquitination of BCL2, thereby acting as a positive CC regulator of autophagy (By similarity). Protects against mitochondrial CC dysfunction during cellular stress, by acting downstream of PINK1 to CC coordinate mitochondrial quality control mechanisms that remove and CC replace dysfunctional mitochondrial components (PubMed:32047033, CC PubMed:25474007, PubMed:22082830, PubMed:24898855). Depending on the CC severity of mitochondrial damage and/or dysfunction, activity ranges CC from preventing apoptosis and stimulating mitochondrial biogenesis to CC regulating mitochondrial dynamics and eliminating severely damaged CC mitochondria via mitophagy (PubMed:32047033, PubMed:22082830, CC PubMed:24898855). Activation and recruitment onto the outer membrane of CC damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated CC phosphorylation of both PRKN and ubiquitin (PubMed:25474007). After CC mitochondrial damage, functions with PINK1 to mediate the decision CC between mitophagy or preventing apoptosis by inducing either the CC poly- or monoubiquitination of VDAC1, respectively; polyubiquitination CC of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 CC decreases mitochondrial calcium influx which ultimately inhibits CC apoptosis (PubMed:32047033). When cellular stress results in CC irreversible mitochondrial damage, promotes the autophagic degradation CC of dysfunctional depolarized mitochondria (mitophagy) by promoting the CC ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, CC MFN1 and USP30 (PubMed:21753002). Preferentially assembles 'Lys-6'-, CC 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to CC mitophagy (By similarity). The PINK1-PRKN pathway also promotes fission CC of damaged mitochondria by PINK1-mediated phosphorylation which CC promotes the PRKN-dependent degradation of mitochondrial proteins CC involved in fission such as MFN2 (PubMed:24192653). This prevents the CC refusion of unhealthy mitochondria with the mitochondrial network or CC initiates mitochondrial fragmentation facilitating their later CC engulfment by autophagosomes (By similarity). Regulates motility of CC damaged mitochondria via the ubiquitination and subsequent degradation CC of MIRO1 and MIRO2; in motor neurons, this likely inhibits CC mitochondrial intracellular anterograde transport along the axons which CC probably increases the chance of the mitochondria undergoing mitophagy CC in the soma (By similarity). Involved in mitochondrial biogenesis via CC the 'Lys-48'-linked polyubiquitination of transcriptional repressor CC ZNF746/PARIS which leads to its subsequent proteasomal degradation and CC allows activation of the transcription factor PPARGC1A (By similarity). CC Limits the production of reactive oxygen species (ROS) (By similarity). CC Regulates cyclin-E during neuronal apoptosis (By similarity). In CC collaboration with CHPF isoform 2, may enhance cell viability and CC protect cells from oxidative stress (PubMed:22082830). Independently of CC its ubiquitin ligase activity, protects from apoptosis by the CC transcriptional repression of p53/TP53 (PubMed:19801972). May protect CC neurons against alpha synuclein toxicity, proteasomal dysfunction, CC GPR37 accumulation, and kainate-induced excitotoxicity (By similarity). CC May play a role in controlling neurotransmitter trafficking at the CC presynaptic terminal and in calcium-dependent exocytosis. May represent CC a tumor suppressor gene (By similarity). {ECO:0000250|UniProtKB:O60260, CC ECO:0000269|PubMed:19801972, ECO:0000269|PubMed:21753002, CC ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:24192653, CC ECO:0000269|PubMed:24898855, ECO:0000269|PubMed:25474007, CC ECO:0000269|PubMed:29311685, ECO:0000269|PubMed:32047033}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.; CC EC=2.3.2.31; Evidence={ECO:0000250|UniProtKB:O60260}; CC -!- ACTIVITY REGULATION: In the autoinhibited state the side chain of Phe- CC 462 inserts into a hydrophobic groove in RING-0, occluding the CC ubiquitin acceptor site Cys-430, whereas the REP repressor element CC binds RING-1 and blocks its E2-binding site. Activation of PRKN CC requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) CC binding to phosphorylated ubiquitin, leading to unlock repression of CC the catalytic Cys-430 by the RING-0 region via an allosteric mechanism CC and converting PRKN to its fully-active form. According to another CC report, phosphorylation at Ser-65 by PINK1 is not essential for CC activation and only binding to phosphorylated ubiquitin is essential to CC unlock repression. In addition, ISG15 conjugation positively regulates CC its ubiquitin E3 ligase activity by suppressing the intramolecular CC interaction that maintains its autoinhibited conformation. CC {ECO:0000250|UniProtKB:O60260}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6. CC Mediates 'Lys-63'-linked polyubiquitination by associating with UBE2V1. CC Part of a SCF-like complex, consisting of PRKN, CUL1 and FBXW7. CC Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11. CC Interacts and regulates the turnover of SEPTIN5. Part of a complex, CC including STUB1, HSP70 and GPR37. The amount of STUB1 in the complex CC increases during ER stress. STUB1 promotes the dissociation of HSP70 CC from PRKN and GPR37, thus facilitating PRKN-mediated GPR37 CC ubiquitination. HSP70 transiently associates with unfolded GPR37 and CC inhibits the E3 activity of PRKN, whereas, STUB1 enhances the E3 CC activity of PRKN through promotion of dissociation of HSP70 from PRKN- CC GPR37 complexes. Interacts with PSMD4 and PACRG. Interacts with LRRK2. CC Interacts with RANBP2. Interacts with SUMO1 but not SUMO2, which CC promotes nuclear localization and autoubiquitination. Interacts (via CC first RING-type domain) with AIMP2 (via N-terminus). Interacts with CC PSMA7 and RNF41. Interacts with PINK1. Forms a complex with PINK1 and CC PARK7. Interacts with CHPF, the interaction with isoform 2 may CC facilitate PRKN transport into the mitochondria. Interacts with MFN2 CC (phosphorylated), promotes PRKN localization in dysfunctional CC depolarized mitochondria. Interacts with FBXO7; this promotes CC translocation to dysfunctional depolarized mitochondria. Interacts with CC ZNF746. Interacts with heat shock protein 70 family members, including CC HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes translocation to CC damaged mitochondria. Interacts with BAG4 and, to a lesser extent, CC BAG5; interaction with BAG4 inhibits translocation to damaged CC mitochondria. Forms a complex with PRKN and PARK7 (By similarity). CC Interacts with AMBRA1 (PubMed:21753002). {ECO:0000250|UniProtKB:O60260, CC ECO:0000269|PubMed:21753002}. CC -!- INTERACTION: CC Q9WVS6; Q6IQX7-2: Chpf; NbExp=3; IntAct=EBI-973635, EBI-9029659; CC Q9WVS6; P47811: Mapk14; NbExp=3; IntAct=EBI-973635, EBI-298727; CC Q9WVS6; Q9ERU9: Ranbp2; NbExp=2; IntAct=EBI-973635, EBI-643756; CC Q9WVS6; P68510: Ywhah; NbExp=2; IntAct=EBI-973635, EBI-444641; CC Q9WVS6; Q3U133: Znf746; NbExp=2; IntAct=EBI-973635, EBI-3862590; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:10818204, CC ECO:0000305|PubMed:11122330}. Nucleus {ECO:0000250|UniProtKB:O60260}. CC Endoplasmic reticulum {ECO:0000269|PubMed:11122330}. Mitochondrion CC {ECO:0000269|PubMed:32047033}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:11122330}. Cell projection, neuron projection CC {ECO:0000269|PubMed:11675120}. Postsynaptic density CC {ECO:0000269|PubMed:11122330}. Presynapse CC {ECO:0000269|PubMed:11122330}. Note=Mainly localizes in the cytosol. CC Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in CC brainstem Lewy bodies. Translocates to dysfunctional mitochondria that CC have lost the mitochondrial membrane potential; recruitment to CC mitochondria is PINK1-dependent. Mitochondrial localization also CC gradually increases with cellular growth. CC {ECO:0000250|UniProtKB:O60260}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9WVS6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9WVS6-2; Sequence=VSP_011714, VSP_011715; CC Name=3; CC IsoId=Q9WVS6-3; Sequence=VSP_011713, VSP_011716; CC -!- TISSUE SPECIFICITY: Expressed in all subdivisions of the brain (at CC protein level) (PubMed:11675120). Highly expressed in brainstem, CC cranial nerve, pontine, cerebellar nuclei, indusium griseum, nuclei CC reticularis, strata oriens and laccunosum moleculare of the hippocampal CC CA2 region (PubMed:11122330). Low levels were found in the CC telencephalon and diencephalon (PubMed:11122330). Expressed in heart, CC liver, skeletal muscle, kidney and testis (PubMed:10818204). CC {ECO:0000269|PubMed:10818204, ECO:0000269|PubMed:11122330, CC ECO:0000269|PubMed:11675120}. CC -!- DEVELOPMENTAL STAGE: In late 10 dpc weakly expressed in postmitotic CC neurons in the mantle layer of the developing nervous system (at CC protein level). Expression increased at 11-12 dpc (at protein level). CC At 15-16 dpc, as more specialized neurons and nonneural cells are CC formed, expression is more tissue specific (at protein level). CC Expression was highest in the neurites, moderate levels were observed CC in the migrating postmitotic neurons in the intermediate and neopallial CC layers (at protein level). In the diencephalon and other CNS regions, CC while the weakest level of expression was observed in the cell bodies CC (at protein level). In nonneural tissues, high levels of expression CC were found in the muscle walls of the intestine, the blood vessels and CC the dermis (at protein level). {ECO:0000269|PubMed:11675120}. CC -!- DOMAIN: The ubiquitin-like domain binds the PSMD4 subunit of 26S CC proteasomes. {ECO:0000250|UniProtKB:O60260}. CC -!- DOMAIN: The RING-type 1 zinc finger domain is required to repress CC p53/TP53 transcription. {ECO:0000250|UniProtKB:O60260}. CC -!- DOMAIN: Members of the RBR family are atypical E3 ligases. They CC interact with the E2 conjugating enzyme UBE2L3 and function like HECT- CC type E3 enzymes: they bind E2s via the first RING domain, but require CC an obligate trans-thiolation step during the ubiquitin transfer, CC requiring a conserved cysteine residue in the second RING domain. CC {ECO:0000250|UniProtKB:O60260}. CC -!- PTM: Auto-ubiquitinates in an E2-dependent manner leading to its own CC degradation. Also polyubiquitinated by RNF41 for proteasomal CC degradation. {ECO:0000250|UniProtKB:O60260}. CC -!- PTM: S-nitrosylated. {ECO:0000269|PubMed:15105460}. CC -!- PTM: Phosphorylated. Activation requires phosphorylation at Ser-65 by CC PINK1 and binding to PINK1 phosphorylated ubiquitin. Phosphorylation at CC Thr-174 by PINK1 and at Thr-216 is important for mitochondrial CC localization. {ECO:0000250|UniProtKB:O60260}. CC -!- DISRUPTION PHENOTYPE: In brain, increased protein levels of p53/TP53 CC and CHPF (PubMed:19801972, PubMed:22082830). Cortical neurons display a CC slight increase in process fragmentation but no dendritic retraction CC (PubMed:24898855). {ECO:0000269|PubMed:19801972, CC ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:24898855}. CC -!- SIMILARITY: Belongs to the RBR family. Parkin subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB019558; BAA82404.1; -; mRNA. DR EMBL; AF250293; AAG13890.1; -; mRNA. DR EMBL; AF250294; AAG13891.1; -; mRNA. DR EMBL; AF250295; AAG13892.1; -; mRNA. DR EMBL; BC113204; AAI13205.1; -; mRNA. DR CCDS; CCDS79506.1; -. [Q9WVS6-1] DR RefSeq; NP_001304655.1; NM_001317726.1. DR RefSeq; NP_057903.1; NM_016694.4. [Q9WVS6-1] DR PDB; 1MG8; NMR; -; A=1-76. DR PDB; 2ZEQ; X-ray; 1.65 A; A=1-76. DR PDB; 3B1L; X-ray; 1.85 A; X=1-76. DR PDBsum; 1MG8; -. DR PDBsum; 2ZEQ; -. DR PDBsum; 3B1L; -. DR AlphaFoldDB; Q9WVS6; -. DR BMRB; Q9WVS6; -. DR SMR; Q9WVS6; -. DR BioGRID; 206136; 33. DR DIP; DIP-37657N; -. DR IntAct; Q9WVS6; 14. DR MINT; Q9WVS6; -. DR STRING; 10090.ENSMUSP00000140587; -. DR iPTMnet; Q9WVS6; -. DR PhosphoSitePlus; Q9WVS6; -. DR SwissPalm; Q9WVS6; -. DR PaxDb; 10090-ENSMUSP00000140587; -. DR ProteomicsDB; 291593; -. [Q9WVS6-1] DR ProteomicsDB; 291594; -. [Q9WVS6-2] DR ProteomicsDB; 291595; -. [Q9WVS6-3] DR Antibodypedia; 4264; 928 antibodies from 51 providers. DR DNASU; 50873; -. DR Ensembl; ENSMUST00000191124.7; ENSMUSP00000140587.2; ENSMUSG00000023826.17. [Q9WVS6-1] DR GeneID; 50873; -. DR KEGG; mmu:50873; -. DR UCSC; uc008akj.1; mouse. [Q9WVS6-3] DR UCSC; uc008akk.1; mouse. [Q9WVS6-1] DR AGR; MGI:1355296; -. DR CTD; 5071; -. DR MGI; MGI:1355296; Prkn. DR VEuPathDB; HostDB:ENSMUSG00000023826; -. DR eggNOG; KOG0006; Eukaryota. DR GeneTree; ENSGT00390000011034; -. DR HOGENOM; CLU_050804_0_0_1; -. DR InParanoid; Q9WVS6; -. DR OMA; DPKWDIK; -. DR OrthoDB; 3084186at2759; -. DR PhylomeDB; Q9WVS6; -. DR Reactome; R-MMU-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death. DR Reactome; R-MMU-5689877; Josephin domain DUBs. DR Reactome; R-MMU-9646399; Aggrephagy. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 50873; 2 hits in 73 CRISPR screens. DR ChiTaRS; Prkn; mouse. DR EvolutionaryTrace; Q9WVS6; -. DR PRO; PR:Q9WVS6; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; Q9WVS6; Protein. DR Bgee; ENSMUSG00000023826; Expressed in hindlimb stylopod muscle and 110 other cell types or tissues. DR ExpressionAtlas; Q9WVS6; baseline and differential. DR GO; GO:0016235; C:aggresome; ISO:MGI. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0098691; C:dopaminergic synapse; IDA:SynGO. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI. DR GO; GO:0000139; C:Golgi membrane; ISO:MGI. DR GO; GO:0097708; C:intracellular vesicle; ISO:MGI. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0099073; C:mitochondrion-derived vesicle; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0016607; C:nuclear speck; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0098793; C:presynapse; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0045202; C:synapse; ISO:MGI. DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI. DR GO; GO:0030672; C:synaptic vesicle membrane; ISO:MGI. DR GO; GO:0043195; C:terminal bouton; ISO:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI. DR GO; GO:0003779; F:actin binding; ISO:MGI. DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI. DR GO; GO:0097602; F:cullin family protein binding; ISO:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:1990444; F:F-box domain binding; ISO:MGI. DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI. DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019900; F:kinase binding; ISO:MGI. DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI. DR GO; GO:0043274; F:phospholipase binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:MGI. DR GO; GO:0003714; F:transcription corepressor activity; ISO:MGI. DR GO; GO:0015631; F:tubulin binding; ISO:MGI. DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI. DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI. DR GO; GO:0070842; P:aggresome assembly; ISO:MGI. DR GO; GO:0000422; P:autophagy of mitochondrion; ISS:UniProtKB. DR GO; GO:1904881; P:cellular response to hydrogen sulfide; ISO:MGI. DR GO; GO:1905232; P:cellular response to L-glutamate; ISO:MGI. DR GO; GO:0097237; P:cellular response to toxic substance; IDA:ParkinsonsUK-UCL. DR GO; GO:0042417; P:dopamine metabolic process; IMP:MGI. DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IMP:MGI. DR GO; GO:0010994; P:free ubiquitin chain polymerization; ISO:MGI. DR GO; GO:0007612; P:learning; IMP:MGI. DR GO; GO:0007626; P:locomotory behavior; IMP:MGI. DR GO; GO:0000266; P:mitochondrial fission; ISS:ParkinsonsUK-UCL. DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; ISO:MGI. DR GO; GO:0051646; P:mitochondrion localization; ISO:MGI. DR GO; GO:0007005; P:mitochondrion organization; ISS:ParkinsonsUK-UCL. DR GO; GO:0099074; P:mitochondrion to lysosome vesicle-mediated transport; ISO:MGI. DR GO; GO:0000423; P:mitophagy; IGI:MGI. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:MGI. DR GO; GO:0044828; P:negative regulation by host of viral genome replication; ISO:MGI. DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; ISO:MGI. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI. DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:1903382; P:negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISO:MGI. DR GO; GO:1903542; P:negative regulation of exosomal secretion; ISO:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:MGI. DR GO; GO:1905366; P:negative regulation of intralumenal vesicle formation; ISO:MGI. DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; ISO:MGI. DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:ParkinsonsUK-UCL. DR GO; GO:0090258; P:negative regulation of mitochondrial fission; ISO:MGI. DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISS:ParkinsonsUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ParkinsonsUK-UCL. DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI. DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:MGI. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:MGI. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI. DR GO; GO:1904049; P:negative regulation of spontaneous neurotransmitter secretion; ISO:MGI. DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:ParkinsonsUK-UCL. DR GO; GO:0042415; P:norepinephrine metabolic process; IMP:MGI. DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; ISO:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISO:MGI. DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; ISO:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:1903861; P:positive regulation of dendrite extension; IGI:ParkinsonsUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISS:ParkinsonsUK-UCL. DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; ISO:MGI. DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI. DR GO; GO:1901526; P:positive regulation of mitophagy; ISO:MGI. DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; ISO:MGI. DR GO; GO:0051582; P:positive regulation of neurotransmitter uptake; ISO:MGI. DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISO:MGI. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:1902530; P:positive regulation of protein linear polyubiquitination; IMP:ParkinsonsUK-UCL. DR GO; GO:1905477; P:positive regulation of protein localization to membrane; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI. DR GO; GO:0010498; P:proteasomal protein catabolic process; ISO:MGI. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI. DR GO; GO:0051865; P:protein autoubiquitination; ISS:ParkinsonsUK-UCL. DR GO; GO:0030163; P:protein catabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0031648; P:protein destabilization; IMP:ParkinsonsUK-UCL. DR GO; GO:0070979; P:protein K11-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISO:MGI. DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0070585; P:protein localization to mitochondrion; IMP:ParkinsonsUK-UCL. DR GO; GO:0019538; P:protein metabolic process; IMP:MGI. DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; ISS:ParkinsonsUK-UCL. DR GO; GO:0050821; P:protein stabilization; ISO:MGI. DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISS:ParkinsonsUK-UCL. DR GO; GO:0042053; P:regulation of dopamine metabolic process; ISO:MGI. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IGI:ParkinsonsUK-UCL. DR GO; GO:0010821; P:regulation of mitochondrion organization; ISS:ParkinsonsUK-UCL. DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IMP:MGI. DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; ISO:MGI. DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI. DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:MGI. DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:MGI. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IDA:SynGO. DR GO; GO:0140251; P:regulation protein catabolic process at presynapse; IDA:SynGO. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL. DR GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL. DR GO; GO:0001964; P:startle response; IMP:MGI. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:MGI. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:MGI. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:ParkinsonsUK-UCL. DR CDD; cd20340; BRcat_RBR_parkin; 1. DR CDD; cd20357; Rcat_RBR_parkin; 1. DR CDD; cd16627; RING-HC_RBR_parkin; 1. DR CDD; cd21382; RING0_parkin; 1. DR CDD; cd01798; Ubl_parkin; 1. DR Gene3D; 1.20.120.1750; -; 1. DR Gene3D; 2.20.25.20; -; 1. DR InterPro; IPR047534; BRcat_RBR_parkin. DR InterPro; IPR031127; E3_UB_ligase_RBR. DR InterPro; IPR002867; IBR_dom. DR InterPro; IPR003977; Parkin. DR InterPro; IPR041565; Parkin_Znf-RING. DR InterPro; IPR047536; Rcat_RBR_parkin. DR InterPro; IPR047535; RING-HC_RBR_parkin. DR InterPro; IPR044066; TRIAD_supradom. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR041170; Znf-RING_14. DR PANTHER; PTHR11685:SF471; E3 UBIQUITIN-PROTEIN LIGASE PARKIN; 1. DR PANTHER; PTHR11685; RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING; 1. DR Pfam; PF00240; ubiquitin; 1. DR Pfam; PF17976; zf-RING_12; 1. DR Pfam; PF17978; zf-RING_14; 1. DR PIRSF; PIRSF037880; Parkin; 1. DR PRINTS; PR01475; PARKIN. DR SMART; SM00647; IBR; 2. DR SMART; SM00213; UBQ; 1. DR SUPFAM; SSF57850; RING/U-box; 2. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS51873; TRIAD; 1. DR PROSITE; PS50053; UBIQUITIN_2; 1. DR Genevisible; Q9WVS6; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Cell projection; Cytoplasm; KW Endoplasmic reticulum; Isopeptide bond; Membrane; Metal-binding; KW Mitochondrion; Mitochondrion outer membrane; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; S-nitrosylation; Synapse; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..464 FT /note="E3 ubiquitin-protein ligase parkin" FT /id="PRO_0000058577" FT DOMAIN 1..76 FT /note="Ubiquitin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214" FT ZN_FING 140..224 FT /note="RING-type 0; atypical" FT ZN_FING 237..292 FT /note="RING-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 312..376 FT /note="IBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 417..448 FT /note="RING-type 2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 70..96 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 77..236 FT /note="Necessary for PINK1-dependent localization to FT mitochondria" FT /evidence="ECO:0000250|UniProtKB:O60260" FT REGION 203..237 FT /note="SYT11 binding 1" FT /evidence="ECO:0000250|UniProtKB:O60260" FT REGION 233..464 FT /note="TRIAD supradomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 256..292 FT /note="SYT11 binding 2" FT /evidence="ECO:0000250|UniProtKB:O60260" FT REGION 377..409 FT /note="REP" FT /evidence="ECO:0000250|UniProtKB:Q9JK66" FT ACT_SITE 430 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 237 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 240 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 252 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 256 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 259 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 262 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 288 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 292 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 331 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 336 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 351 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 359 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 364 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 367 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 372 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 376 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 417 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 420 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 435 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 440 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 445 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 448 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 456 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 460 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT MOD_RES 65 FT /note="Phosphoserine; by PINK1" FT /evidence="ECO:0000250|UniProtKB:O60260" FT MOD_RES 80 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 174 FT /note="Phosphothreonine; by PINK1" FT /evidence="ECO:0000250|UniProtKB:O60260" FT MOD_RES 216 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O60260" FT CROSSLNK 348 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000250|UniProtKB:O60260" FT CROSSLNK 368 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000250|UniProtKB:O60260" FT VAR_SEQ 244..261 FT /note="RSPVLVFQCNHRHVICLD -> SHLPLSSGASVWTRPHLH (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:11122330" FT /id="VSP_011713" FT VAR_SEQ 245..254 FT /note="SPVLVFQCNH -> FMRMSKHRTS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11122330" FT /id="VSP_011714" FT VAR_SEQ 255..464 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11122330" FT /id="VSP_011715" FT VAR_SEQ 262..464 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11122330" FT /id="VSP_011716" FT CONFLICT 137 FT /note="P -> PA (in Ref. 1 and 2; AAG13890)" FT /evidence="ECO:0000305" FT STRAND 1..11 FT /evidence="ECO:0007829|PDB:2ZEQ" FT STRAND 13..17 FT /evidence="ECO:0007829|PDB:2ZEQ" FT HELIX 23..34 FT /evidence="ECO:0007829|PDB:2ZEQ" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:2ZEQ" FT STRAND 41..45 FT /evidence="ECO:0007829|PDB:2ZEQ" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:2ZEQ" FT HELIX 56..58 FT /evidence="ECO:0007829|PDB:2ZEQ" FT STRAND 66..73 FT /evidence="ECO:0007829|PDB:2ZEQ" SQ SEQUENCE 464 AA; 51618 MW; 5574A285A9A1B080 CRC64; MIVFVRFNSS YGFPVEVDSD TSILQLKEVV AKRQGVPADQ LRVIFAGKEL PNHLTVQNCD LEQQSIVHIV QRPRRRSHET NASGGDEPQS TSEGSIWESR SLTRVDLSSH TLPVDSVGLA VILDTDSKRD SEAARGPVKP TYNSFFIYCK GPCHKVQPGK LRVQCGTCKQ ATLTLAQGPS CWDDVLIPNR MSGECQSPDC PGTRAEFFFK CGAHPTSDKD TSVALNLITS NRRSIPCIAC TDVRSPVLVF QCNHRHVICL DCFHLYCVTR LNDRQFVHDA QLGYSLPCVA GCPNSLIKEL HHFRILGEEQ YTRYQQYGAE ECVLQMGGVL CPRPGCGAGL LPEQGQRKVT CEGGNGLGCG FVFCRDCKEA YHEGDCDSLL EPSGATSQAY RVDKRAAEQA RWEEASKETI KKTTKPCPRC NVPIEKNGGC MHMKCPQPQC KLEWCWNCGC EWNRACMGDH WFDV //