Prkn

Functionⁱ

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', '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 a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. 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. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. 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. May represent a tumor suppressor gene.

By similarity

Catalytic activityⁱ

[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.
1 Publication
Manual assertion based on experiment inⁱ
- Ref.7
  "Structure of parkin reveals mechanisms for ubiquitin ligase activation."
  Trempe J.F., Sauve V., Grenier K., Seirafi M., Tang M.Y., Menade M., Al-Abdul-Wahid S., Krett J., Wong K., Kozlov G., Nagar B., Fon E.A., Gehring K.
  Science 340:1451-1455(2013) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (6.5 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 141-465, RING-TYPE ZINC-FINGERS, CATALYTIC ACTIVITY, ACTIVE SITE, AUTOUBIQUITINATION, ACTIVITY REGULATION, MUTAGENESIS OF TRP-403.
EC:2.3.2.31

Activity regulationⁱ

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. 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. 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.By similarity1 Publication

Pathwayⁱ: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	238	Zinc 1PROSITE-ProRule annotation	1
Metal bindingⁱ	241	Zinc 1PROSITE-ProRule annotation	1
Metal bindingⁱ	253	Zinc 2PROSITE-ProRule annotation	1
Metal bindingⁱ	257	Zinc 2; via pros nitrogenPROSITE-ProRule annotation	1
Metal bindingⁱ	260	Zinc 1PROSITE-ProRule annotation	1
Metal bindingⁱ	263	Zinc 1PROSITE-ProRule annotation	1
Metal bindingⁱ	289	Zinc 2PROSITE-ProRule annotation	1
Metal bindingⁱ	293	Zinc 2PROSITE-ProRule annotation	1
Metal bindingⁱ	332	Zinc 3PROSITE-ProRule annotation	1
Metal bindingⁱ	337	Zinc 3PROSITE-ProRule annotation	1
Metal bindingⁱ	352	Zinc 3PROSITE-ProRule annotation	1
Metal bindingⁱ	360	Zinc 3PROSITE-ProRule annotation	1
Metal bindingⁱ	365	Zinc 4PROSITE-ProRule annotation	1
Metal bindingⁱ	368	Zinc 4PROSITE-ProRule annotation	1
Metal bindingⁱ	373	Zinc 4; via tele nitrogenPROSITE-ProRule annotation	1
Metal bindingⁱ	377	Zinc 4PROSITE-ProRule annotation	1
Metal bindingⁱ	418	Zinc 5PROSITE-ProRule annotation	1
Metal bindingⁱ	421	Zinc 5PROSITE-ProRule annotation	1
Active siteⁱ	431	PROSITE-ProRule annotation1 Publication	1
Metal bindingⁱ	436	Zinc 5PROSITE-ProRule annotation	1
Metal bindingⁱ	441	Zinc 5PROSITE-ProRule annotation	1
Metal bindingⁱ	446	Zinc 6PROSITE-ProRule annotation	1
Metal bindingⁱ	449	Zinc 6PROSITE-ProRule annotation	1
Metal bindingⁱ	457	Zinc 6PROSITE-ProRule annotation	1
Metal bindingⁱ	461	Zinc 6; via tele nitrogenPROSITE-ProRule annotation	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	141 – 225	RING-type 0; atypicalAdd BLAST	85
Zinc fingerⁱ	238 – 293	RING-type 1PROSITE-ProRule annotationAdd BLAST	56
Zinc fingerⁱ	313 – 377	IBR-typePROSITE-ProRule annotationAdd BLAST	65
Zinc fingerⁱ	418 – 449	RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST	32

GO - Molecular functionⁱ

actin binding Source: RGD
beta-catenin binding Source: RGD
chaperone binding Source: RGD
cullin family protein binding Source: ParkinsonsUK-UCL
enzyme binding Source: RGD
F-box domain binding Source: ParkinsonsUK-UCL
G protein-coupled receptor binding Source: ParkinsonsUK-UCL
heat shock protein binding Source: RGD
histone deacetylase binding Source: RGD
Hsp70 protein binding Source: RGD
identical protein binding Source: ParkinsonsUK-UCL
kinase binding Source: RGD
metal ion binding Source: UniProtKB-KW
PDZ domain binding Source: ParkinsonsUK-UCL
phospholipase binding Source: RGD
protein-containing complex binding
Source: RGD
Inferred from direct assayⁱ
- "Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation."
  Ren Y., Zhao J., Feng J.
  J Neurosci 23:3316-3324(2003) [PubMed] [Europe PMC] [Abstract]
protein kinase binding
Source: RGD
Inferred from physical interactionⁱ
- "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
  Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
  J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
transcription corepressor activity Source: RGD
tubulin binding Source: RGD
ubiquitin binding Source: UniProtKB
ubiquitin conjugating enzyme binding Source: ParkinsonsUK-UCL
ubiquitin protein ligase activity Source: UniProtKB
ubiquitin protein ligase binding Source: RGD
ubiquitin-protein transferase activity Source: UniProtKB
ubiquitin-specific protease binding Source: RGD

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Transferase
Biological process	Autophagy, Transcription, Transcription regulation, Ubl conjugation pathway
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayⁱ	UPA00143

UniPathwayⁱ

UPA00143

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: E3 ubiquitin-protein ligase parkinCurated (EC:2.3.2.311 Publication) Alternative name(s): Parkin RBR E3 ubiquitin-protein ligaseBy similarity
Gene namesⁱ	Name:PrknBy similarity Synonyms:Park2Imported
Organismⁱ	Rattus norvegicus (Rat)
Taxonomic identifierⁱ	10116 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesⁱ	UP000002494 Componentⁱ: Unplaced

Organism-specific databases

Rat genome database More...RGDⁱ	61797, Prkn

RGDⁱ

61797, Prkn

Keywords - Cellular componentⁱ

Cell junction, Cell projection, Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus, Synapse

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	403	W → A: Increased autoubiquitination. 1 Publication		1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000058578	1 – 465	E3 ubiquitin-protein ligase parkinAdd BLAST		465

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	65	Phosphoserine; by PINK1By similarity	1
Modified residueⁱ	80	PhosphothreonineBy similarity	1
Modified residueⁱ	175	Phosphothreonine; by PINK1By similarity	1
Modified residueⁱ	217	PhosphothreonineBy similarity	1

Post-translational modificationⁱ

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation (PubMed:23661642). Also polyubiquitinated by RNF41 for proteasomal degradation (By similarity).By similarity1 Publication

S-nitrosylated.By similarity

Phosphorylated. Activation requires phosphorylation at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin. Phosphorylation at Thr-175 by PINK1 and at Thr-217 is important for mitochondrial localization.By similarity

Keywords - PTMⁱ

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbⁱ	Q9JK66

PaxDbⁱ

Q9JK66

PTM databases

iPTMnetⁱ	Q9JK66
PhosphoSitePlusⁱ	Q9JK66

Expressionⁱ

Tissue specificityⁱ

Largely confined to neuronal elements, including fibers and neuropil. Highly expressed at the forebrain level, in pyramidal cells of layer V, in various cortical regions and cerebellum. Expressed in the nucleus of diagonal band of Broca, nucleus basalis, bed nucleus of the stria terminalis, and olfactory tubercle. Moderate expression is seen in most neurons of the subthalamic nucleus, heart, skeletal muscle and testis. Moderate expression was found in frontal cortex, parietal cortex, cerebellum, heart, skeletal muscle and testis.1 Publication

Interactionⁱ

Subunit structureⁱ

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.

Forms a complex with PINK1 and PARK7.

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 ZNF746.

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 PRKN and PARK7.

Interacts with AMBRA1 (By similarity).

By similarity

Binary interactionsⁱ

Q9JK66

With	#Exp.	IntAct
Ranbp2 [D4A054]	2	EBI-973793,EBI-973937

GO - Molecular functionⁱ

actin binding Source: RGD
beta-catenin binding Source: RGD
chaperone binding Source: RGD
cullin family protein binding Source: ParkinsonsUK-UCL
enzyme binding Source: RGD
F-box domain binding Source: ParkinsonsUK-UCL
G protein-coupled receptor binding Source: ParkinsonsUK-UCL
heat shock protein binding Source: RGD
histone deacetylase binding Source: RGD
Hsp70 protein binding Source: RGD
identical protein binding Source: ParkinsonsUK-UCL
kinase binding Source: RGD
PDZ domain binding Source: ParkinsonsUK-UCL
phospholipase binding Source: RGD
protein kinase binding
Source: RGD
Inferred from physical interactionⁱ
- "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
  Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
  J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
tubulin binding Source: RGD
ubiquitin binding Source: UniProtKB
ubiquitin conjugating enzyme binding Source: ParkinsonsUK-UCL
ubiquitin protein ligase binding Source: RGD
ubiquitin-specific protease binding Source: RGD

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	248590, 17 interactors
Database of interacting proteins More...DIPⁱ	DIP-37656N
IntActⁱ	Q9JK66, 1 interactor
Molecular INTeraction database More...MINTⁱ	Q9JK66
STRINGⁱ	10116.ENSRNOP00000040511

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	2 – 11	Combined sources	10
Beta strandⁱ	13 – 16	Combined sources	4
Helixⁱ	23 – 34	Combined sources	12
Helixⁱ	38 – 40	Combined sources	3
Beta strandⁱ	41 – 45	Combined sources	5
Beta strandⁱ	48 – 50	Combined sources	3
Helixⁱ	56 – 59	Combined sources	4
Beta strandⁱ	65 – 71	Combined sources	7
Beta strandⁱ	147 – 150	Combined sources	4
Turnⁱ	151 – 154	Combined sources	4
Beta strandⁱ	156 – 166	Combined sources	11
Turnⁱ	167 – 170	Combined sources	4
Beta strandⁱ	174 – 178	Combined sources	5
Helixⁱ	183 – 187	Combined sources	5
Beta strandⁱ	193 – 196	Combined sources	4
Beta strandⁱ	205 – 215	Combined sources	11
Beta strandⁱ	223 – 225	Combined sources	3
Turnⁱ	239 – 241	Combined sources	3
Beta strandⁱ	246 – 250	Combined sources	5
Beta strandⁱ	253 – 255	Combined sources	3
Beta strandⁱ	257 – 260	Combined sources	4
Helixⁱ	261 – 274	Combined sources	14
Beta strandⁱ	278 – 280	Combined sources	3
Turnⁱ	281 – 283	Combined sources	3
Beta strandⁱ	284 – 286	Combined sources	3
Helixⁱ	301 – 307	Combined sources	7
Helixⁱ	309 – 316	Combined sources	8
Helixⁱ	318 – 326	Combined sources	9
Turnⁱ	335 – 337	Combined sources	3
Beta strandⁱ	348 – 350	Combined sources	3
Helixⁱ	355 – 357	Combined sources	3
Beta strandⁱ	363 – 365	Combined sources	3
Beta strandⁱ	366 – 368	Combined sources	3
Helixⁱ	395 – 400	Combined sources	6
Beta strandⁱ	401 – 403	Combined sources	3
Beta strandⁱ	415 – 417	Combined sources	3
Turnⁱ	419 – 421	Combined sources	3
Beta strandⁱ	424 – 426	Combined sources	3
Beta strandⁱ	429 – 431	Combined sources	3
Beta strandⁱ	433 – 435	Combined sources	3
Turnⁱ	439 – 441	Combined sources	3
Beta strandⁱ	444 – 446	Combined sources	3
Turnⁱ	447 – 449	Combined sources	3
Helixⁱ	455 – 461	Combined sources	7

Show more details

3D structure databases

AlphaFoldDBⁱ	Q9JK66
BMRBⁱ	Q9JK66
SMRⁱ	Q9JK66
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ

Q9JK66

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	1 – 76	Ubiquitin-likePROSITE-ProRule annotationAdd BLAST		76

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	71 – 96	DisorderedSequence analysisAdd BLAST	26
Regionⁱ	77 – 237	Necessary for PINK1-dependent localization to mitochondriaBy similarityAdd BLAST	161
Regionⁱ	204 – 238	SYT11 binding 1By similarityAdd BLAST	35
Regionⁱ	234 – 465	TRIAD supradomainPROSITE-ProRule annotationAdd BLAST	232
Regionⁱ	257 – 293	SYT11 binding 2By similarityAdd BLAST	37
Regionⁱ	378 – 410	REP1 PublicationAdd BLAST	33

Domainⁱ

The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.By similarity

The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.By similarity

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.By similarity

Sequence similaritiesⁱ

Belongs to the RBR family. Parkin subfamily.Curated

Zinc finger

Feature key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	141 – 225	RING-type 0; atypicalAdd BLAST	85
Zinc fingerⁱ	238 – 293	RING-type 1PROSITE-ProRule annotationAdd BLAST	56
Zinc fingerⁱ	313 – 377	IBR-typePROSITE-ProRule annotationAdd BLAST	65
Zinc fingerⁱ	418 – 449	RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST	32

Keywords - Domainⁱ

Repeat, Zinc-finger

Phylogenomic databases

eggNOGⁱ	KOG0006, Eukaryota
InParanoidⁱ	Q9JK66
Database of Orthologous Groups More...OrthoDBⁱ	1140368at2759
PhylomeDBⁱ	Q9JK66

Family and domain databases

Database of protein disorder More...DisProtⁱ	DP01850
InterProⁱ	View protein in InterPro IPR002867, IBR_dom IPR003977, Parkin IPR041565, Parkin_Znf-RING IPR044066, TRIAD_supradom IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR041170, Znf-RING_14
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01485, IBR, 1 hit PF00240, ubiquitin, 1 hit PF17976, zf-RING_12, 1 hit PF17978, zf-RING_14, 1 hit
PIRSFⁱ	PIRSF037880, Parkin, 1 hit
PRINTSⁱ	PR01475, PARKIN
SMARTⁱ	View protein in SMART SM00647, IBR, 2 hits SM00213, UBQ, 1 hit
SUPFAMⁱ	SSF54236, SSF54236, 1 hit
PROSITEⁱ	View protein in PROSITE PS51873, TRIAD, 1 hit PS50053, UBIQUITIN_2, 1 hit

Sequences (6+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 6 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 6 described isoforms and 8 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q9JK66-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the canonicalⁱ sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQGP SCWDDVLIPN RMSGECQSPD 
       210        220        230        240        250
CPGTRAEFFF KCGAHPTSDK DTSVALNLIT NNSRSIPCIA CTDVRNPVLV 
       260        270        280        290        300
FQCNHRHVIC LDCFHLYCVT RLNDRQFVHD AQLGYSLPCV AGCPNSLIKE 
       310        320        330        340        350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEQGQKKV 
       360        370        380        390        400
TCEGGNGLGC GFVFCRDCKE AYHEGECDSM FEASGATSQA YRVDQRAAEQ 
       410        420        430        440        450
ARWEEASKET IKKTTKPCPR CNVPIEKNGG CMHMKCPQPQ CKLEWCWNCG 
       460 
CEWNRACMGD HWFDV

Length:465

Mass (Da):51,709

Last modified:October 1, 2000 - v1

Checksum:ⁱE13CF170AD6D042B

GO

Isoform 2 (identifier: Q9JK66-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
429-446: GGCMHMKCPQPQCKLEWC → ERMHVQYTMCIPGAHGGY
447-465: Missing.

« Hide

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQGP SCWDDVLIPN RMSGECQSPD 
       210        220        230        240        250
CPGTRAEFFF KCGAHPTSDK DTSVALNLIT NNSRSIPCIA CTDVRNPVLV 
       260        270        280        290        300
FQCNHRHVIC LDCFHLYCVT RLNDRQFVHD AQLGYSLPCV AGCPNSLIKE 
       310        320        330        340        350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEQGQKKV 
       360        370        380        390        400
TCEGGNGLGC GFVFCRDCKE AYHEGECDSM FEASGATSQA YRVDQRAAEQ 
       410        420        430        440 
ARWEEASKET IKKTTKPCPR CNVPIEKNER MHVQYTMCIP GAHGGY

Show »

Length:446

Mass (Da):49,368

Checksum:ⁱF06FAF788531DF5C

GO

Isoform 3 (identifier: Q9JK66-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-191: Missing.

« Hide

        10         20         30         40         50
MSGECQSPDC PGTRAEFFFK CGAHPTSDKD TSVALNLITN NSRSIPCIAC 
        60         70         80         90        100
TDVRNPVLVF QCNHRHVICL DCFHLYCVTR LNDRQFVHDA QLGYSLPCVA 
       110        120        130        140        150
GCPNSLIKEL HHFRILGEEQ YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL 
       160        170        180        190        200
LPEQGQKKVT CEGGNGLGCG FVFCRDCKEA YHEGECDSMF EASGATSQAY 
       210        220        230        240        250
RVDQRAAEQA RWEEASKETI KKTTKPCPRC NVPIEKNGGC MHMKCPQPQC 
       260        270 
KLEWCWNCGC EWNRACMGDH WFDV

Show »

Length:274

Mass (Da):30,642

Checksum:ⁱB29BB58E86EB5DFE

GO

Isoform 4 (identifier: Q9JK66-4) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
57-57: Q → QHPQDGFCHKSHLAVHNLSQQDVTQ

« Hide

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQHPQ DGFCHKSHLA VHNLSQQDVT QNCDLEQQSI VHIVQRPQRK 
       110        120        130        140        150
SHETNASGGD KPQSTPEGSI WEPRSLTRVD LSSHILPADS VGLAVILDTD 
       160        170        180        190        200
SKSDSEAARG PEAKPTYHSF FVYCKGPCHK VQPGKLRVQC GTCRQATLTL 
       210        220        230        240        250
AQGPSCWDDV LIPNRMSGEC QSPDCPGTRA EFFFKCGAHP TSDKDTSVAL 
       260        270        280        290        300
NLITNNSRSI PCIACTDVRN PVLVFQCNHR HVICLDCFHL YCVTRLNDRQ 
       310        320        330        340        350
FVHDAQLGYS LPCVAGCPNS LIKELHHFRI LGEEQYNRYQ QYGAEECVLQ 
       360        370        380        390        400
MGGVLCPRPG CGAGLLPEQG QKKVTCEGGN GLGCGFVFCR DCKEAYHEGE 
       410        420        430        440        450
CDSMFEASGA TSQAYRVDQR AAEQARWEEA SKETIKKTTK PCPRCNVPIE 
       460        470        480 
KNGGCMHMKC PQPQCKLEWC WNCGCEWNRA CMGDHWFDV

Show »

Length:489

Mass (Da):54,418

Checksum:ⁱ49F53B8F358E2AB5

GO

Isoform 5 (identifier: Q9JK66-5) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
179-206: Missing.

« Hide

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQEF FFKCGAHPTS DKDTSVALNL 
       210        220        230        240        250
ITNNSRSIPC IACTDVRNPV LVFQCNHRHV ICLDCFHLYC VTRLNDRQFV 
       260        270        280        290        300
HDAQLGYSLP CVAGCPNSLI KELHHFRILG EEQYNRYQQY GAEECVLQMG 
       310        320        330        340        350
GVLCPRPGCG AGLLPEQGQK KVTCEGGNGL GCGFVFCRDC KEAYHEGECD 
       360        370        380        390        400
SMFEASGATS QAYRVDQRAA EQARWEEASK ETIKKTTKPC PRCNVPIEKN 
       410        420        430 
GGCMHMKCPQ PQCKLEWCWN CGCEWNRACM GDHWFDV

Show »

Length:437

Mass (Da):48,734

Checksum:ⁱ3227286E41EBE5E3

GO

Isoform 6 (identifier: Q9JK66-6) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.
     390-394: AYRVD → EDVCT
     395-465: Missing.

« Hide

        10         20         30         40         50
MSGECQSPDC PGTRAEFFFK CGAHPTSDKD TSVALNLITN NSRSIPCIAC 
        60         70         80         90        100
TDVRNPVLVF QCNHRHVICL DCFHLYCVTR LNDRQFVHDA QLGYSLPCVA 
       110        120        130        140        150
GCPNSLIKEL HHFRILGEEQ YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL 
       160        170        180        190        200
LPEQGQKKVT CEGGNGLGCG FVFCRDCKEA YHEGECDSMF EASGATSQED 

VCT

Show »

Length:203

Mass (Da):22,288

Checksum:ⁱ3CFF551C49EB0783

GO

Computationally mapped potential isoform sequencesⁱ

There are 8 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

D3JVU5	D3JVU5_RAT	E3 ubiquitin-protein ligase parkin E3 ubiquitin-protein ligase parkin (Truncated parkin variant SV2bINS, EC 6.3.2.19)	Prkn Park2	79	Annotation score:
A0A0G2JY87	A0A0G2JY87_RAT	RBR-type E3 ubiquitin transferase RBR-type E3 ubiquitin transferase, EC 2.3.2.31	Prkn	210	Annotation score:
A0A0G2K740	A0A0G2K740_RAT	RBR-type E3 ubiquitin transferase RBR-type E3 ubiquitin transferase, EC 2.3.2.31	Prkn	488	Annotation score:
A0A0G2K2J2	A0A0G2K2J2_RAT	RBR-type E3 ubiquitin transferase RBR-type E3 ubiquitin transferase, EC 2.3.2.31	Prkn	182	Annotation score:
A0A0G2JZS8	A0A0G2JZS8_RAT	E3 ubiquitin-protein ligase parkin E3 ubiquitin-protein ligase parkin	Prkn	343	Annotation score:
A0A8I5ZN83	A0A8I5ZN83_RAT	E3 ubiquitin-protein ligase parkin E3 ubiquitin-protein ligase parkin	Prkn	101	Annotation score:
A0A8I6A5N7	A0A8I6A5N7_RAT	E3 ubiquitin-protein ligase parkin E3 ubiquitin-protein ligase parkin	Prkn	493	Annotation score:
A0A8I6GIU4	A0A8I6GIU4_RAT	E3 ubiquitin-protein ligase parkin E3 ubiquitin-protein ligase parkin	Prkn	436	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	24	F → C in AAF34874 (PubMed:10686358).Curated	1
Sequence conflictⁱ	138	E → A in BAA92431 (Ref. 3) Curated	1
Sequence conflictⁱ	348	K → R in BAA92431 (Ref. 3) Curated	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_011717	1 – 191	Missing in isoform 3 and isoform 6. 1 PublicationAdd BLAST	191
Alternative sequenceⁱVSP_011718	57	Q → QHPQDGFCHKSHLAVHNLSQ QDVTQ in isoform 4. 1 Publication	1
Alternative sequenceⁱVSP_011719	179 – 206	Missing in isoform 5. 1 PublicationAdd BLAST	28
Alternative sequenceⁱVSP_011720	390 – 394	AYRVD → EDVCT in isoform 6. 1 Publication	5
Alternative sequenceⁱVSP_011721	395 – 465	Missing in isoform 6. 1 PublicationAdd BLAST	71
Alternative sequenceⁱVSP_011722	429 – 446	GGCMH…KLEWC → ERMHVQYTMCIPGAHGGY in isoform 2. 1 PublicationAdd BLAST	18
Alternative sequenceⁱVSP_011723	447 – 465	Missing in isoform 2. 1 PublicationAdd BLAST	19

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF343574 mRNA Translation: AAL73348.1 AF381277 mRNA Translation: AAM21452.1 AF381278 mRNA Translation: AAM21453.1 AF381279 mRNA Translation: AAM21454.1 AF381280 mRNA Translation: AAM21455.1 AF381281 mRNA Translation: AAM21456.1 AF168004 mRNA Translation: AAF34874.1 AF210434 mRNA Translation: AAG37013.1 AF257234 mRNA Translation: AAF68666.1 AB039878 mRNA Translation: BAA92431.1
NCBI Reference Sequences More...RefSeqⁱ	NP_064478.1, NM_020093.1

Genome annotation databases

Ensemblⁱ	ENSRNOT00000096213; ENSRNOP00000077507; ENSRNOG00000055547 [Q9JK66-1] ENSRNOT00000107769; ENSRNOP00000088932; ENSRNOG00000055547 [Q9JK66-3]
GeneIDⁱ	56816
KEGGⁱ	rno:56816

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins	Species	Length	Source
Q9JK66-3	RBR-type E3 ubiquitin transferase	RAT	86	UniRef100_S4X0T3
+2
Q9JK66-6	E3 ubiquitin-protein ligase parkin	RAT	394	UniRef100_D3JW63

Protein	Similar proteins		Species	Score	Length	Source
Q9JK66	E3 ubiquitin-protein ligase parkin	)	MOUSE		464	UniRef90_Q9JK66
E3 ubiquitin-protein ligase parkin		RAT		494
E3 ubiquitin-protein ligase parkin		MUSCR		465
E3 ubiquitin-protein ligase parkin		PERMB		464
E3 ubiquitin-protein ligase parkin		CRIGR		464
+58
Q9JK66-6	E3 ubiquitin-protein ligase parkin		RAT		394	UniRef90_D3JW63

Protein	Similar proteins		Species	Score	Length	Source
Q9JK66	E3 ubiquitin-protein ligase parkin	)	MOUSE		464	UniRef50_Q9JK66
E3 ubiquitin-protein ligase parkin		RAT		494
E3 ubiquitin-protein ligase parkin		MUSCR		465
E3 ubiquitin-protein ligase parkin		PERMB		464
E3 ubiquitin-protein ligase parkin		CRIGR		464
+247
Q9JK66-6	Isoform 6 of E3 ubiquitin-protein ligase parkin		HUMAN		316	UniRef50_O60260-6
E3 ubiquitin-protein ligase parkin		RAT		344
E3 ubiquitin-protein ligase parkin		Ugandan red Colobus		316
E3 ubiquitin-protein ligase parkin		MACNE		316
E3 ubiquitin-protein ligase parkin		RHIRO		316
+59

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF343574 mRNA Translation: AAL73348.1 AF381277 mRNA Translation: AAM21452.1 AF381278 mRNA Translation: AAM21453.1 AF381279 mRNA Translation: AAM21454.1 AF381280 mRNA Translation: AAM21455.1 AF381281 mRNA Translation: AAM21456.1 AF168004 mRNA Translation: AAF34874.1 AF210434 mRNA Translation: AAG37013.1 AF257234 mRNA Translation: AAF68666.1 AB039878 mRNA Translation: BAA92431.1
RefSeqⁱ	NP_064478.1, NM_020093.1

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2KNB	NMR	-	A	1-76	[»]
	4K7D	X-ray	2.80	A/B/C	141-465	[»]
	4K95	X-ray	6.50	A/B/C/D/E/F/G/H/I/J/K/L	1-465	[»]
	4ZYN	X-ray	2.54	A/B	1-465	[»]
AlphaFoldDBⁱ	Q9JK66
BMRBⁱ	Q9JK66
SMRⁱ	Q9JK66
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	248590, 17 interactors
DIPⁱ	DIP-37656N
IntActⁱ	Q9JK66, 1 interactor
MINTⁱ	Q9JK66
STRINGⁱ	10116.ENSRNOP00000040511

PTM databases

iPTMnetⁱ	Q9JK66
PhosphoSitePlusⁱ	Q9JK66

Proteomic databases

PaxDbⁱ	Q9JK66

PaxDbⁱ

Q9JK66

Genome annotation databases

Ensemblⁱ	ENSRNOT00000096213; ENSRNOP00000077507; ENSRNOG00000055547 [Q9JK66-1] ENSRNOT00000107769; ENSRNOP00000088932; ENSRNOG00000055547 [Q9JK66-3]
GeneIDⁱ	56816
KEGGⁱ	rno:56816

Organism-specific databases

CTDⁱ	5071
RGDⁱ	61797, Prkn

Phylogenomic databases

eggNOGⁱ	KOG0006, Eukaryota
InParanoidⁱ	Q9JK66
OrthoDBⁱ	1140368at2759
PhylomeDBⁱ	Q9JK66

Enzyme and pathway databases

UniPathwayⁱ	UPA00143

UniPathwayⁱ

UPA00143

Miscellaneous databases

EvolutionaryTraceⁱ	Q9JK66
Protein Ontology More...PROⁱ	PR:Q9JK66

Family and domain databases

DisProtⁱ	DP01850
InterProⁱ	View protein in InterPro IPR002867, IBR_dom IPR003977, Parkin IPR041565, Parkin_Znf-RING IPR044066, TRIAD_supradom IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR041170, Znf-RING_14
Pfamⁱ	View protein in Pfam PF01485, IBR, 1 hit PF00240, ubiquitin, 1 hit PF17976, zf-RING_12, 1 hit PF17978, zf-RING_14, 1 hit
PIRSFⁱ	PIRSF037880, Parkin, 1 hit
PRINTSⁱ	PR01475, PARKIN
SMARTⁱ	View protein in SMART SM00647, IBR, 2 hits SM00213, UBQ, 1 hit
SUPFAMⁱ	SSF54236, SSF54236, 1 hit
PROSITEⁱ	View protein in PROSITE PS51873, TRIAD, 1 hit PS50053, UBIQUITIN_2, 1 hit
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PRKN_RAT
Accessionⁱ	Q9JK66Primary (citable) accession number: Q9JK66 Secondary accession number(s): Q8K5C3 Q9JM64
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
	Last sequence update:	October 1, 2000
	Last modified:	May 25, 2022
	This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

UniProtKB

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UniProtKB - Q9JK66 (PRKN_RAT)

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E3 ubiquitin-protein ligase parkin

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Endoplasmic reticulum

Cytoplasm and Cytosol

Mitochondrion

Other locations

Cytosol

Endoplasmic reticulum

Golgi apparatus

Mitochondrion

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Q9JK66

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

Catalytic activityⁱ

Pathwayⁱ: protein ubiquitination

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ