O60260 (PRKN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase parkin
EC=6.3.2.-

Alternative name(s):
Parkinson juvenile disease protein 2
Short name=Parkinson disease protein 2

Gene names

Name:	PARK2
Synonyms:	PRKN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene. Ref.10 Ref.11 Ref.20 Ref.22 Ref.24 Ref.26 Ref.27 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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 PARK2, CUL1 and FBXW7. Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11. Interacts and regulates the turnover of SEPT5. 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 PARK2 and GPR37, thus facilitating PARK2-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PARK2, whereas, STUB1 enhances the E3 activity of PARK2 through promotion of dissociation of HSP70 from PARK2-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. Ref.12 Ref.14 Ref.17 Ref.18 Ref.19 Ref.20 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39
Subcellular location	Cytoplasm › cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Note: Mainly localizes in the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies. Relocates to dysfunctional mitochondria that have lost the mitochondial membrane potential; recruitement to mitochondria is PINK1-dependent. Ref.2 Ref.9 Ref.15 Ref.30 Ref.31 Ref.32 Ref.35 Ref.36
Tissue specificity	Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Found in serum (at protein level). Ref.2
Domain	The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes. Ref.16
Post-translational modification	Auto-ubiquitinates in an E2-dependent manner leading to its own degradation. Also polyubiquitinated by RNF41 for proteasomal degradation. S-nitrosylated. The inhibition of PARK2 ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PARK2 substrates.
Involvement in disease	Defects in PARK2 are a cause of Parkinson disease (PARK) [MIM:168600]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. Ref.1 Ref.11 Ref.14 Ref.15 Ref.18 Ref.35 Ref.36 Ref.37 Ref.40 Ref.42 Ref.44 Ref.46 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.62 Defects in PARK2 are the cause of Parkinson disease type 2 (PARK2) [MIM:600116]; also known as early-onset parkinsonism with diurnal fluctuation (EPDF) or autosomal recessive juvenile Parkinson disease (PDJ). A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually befor 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent. Ref.1 Ref.14 Ref.35 Ref.40 Ref.42 Ref.44 Ref.46 Ref.50 Ref.51 Ref.54 Note=Defects in PARK2 may be involved in the development and/or progression of ovarian cancer.
Miscellaneous	The parkin locus (PRKN), adjacent to the 6q telomere is hyper-recombinable and lies within FRA6E, the third most common fragile site in tumor tissue. 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 (Ref.38).
Sequence similarities	Belongs to the RBR family. Parkin subfamily. Contains 1 IBR-type zinc finger. Contains 2 RING-type zinc fingers. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Autophagy Ubl conjugation pathway
Cellular component	Cytoplasm Endoplasmic reticulum Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Neurodegeneration Parkinson disease Parkinsonism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	aggresome assembly Inferred from mutant phenotype. Source: BHF-UCL central nervous system development Traceable author statement. Source: ProtInc mitochondrion degradation Inferred from mutant phenotype Ref.32. Source: UniProtKB negative regulation of actin filament bundle assembly Inferred from direct assay. Source: BHF-UCL negative regulation of cell death Inferred from direct assay. Source: BHF-UCL negative regulation of protein phosphorylation Inferred from direct assay. Source: BHF-UCL negative regulation of release of cytochrome c from mitochondria Inferred from direct assay. Source: BHF-UCL neuron death Inferred from direct assay Ref.37. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay. Source: BHF-UCL protein K48-linked ubiquitination Inferred from direct assay Ref.37. Source: UniProtKB protein K63-linked ubiquitination Inferred from direct assay Ref.26. Source: UniProtKB protein autoubiquitination Inferred from direct assay Ref.26. Source: UniProtKB protein monoubiquitination Inferred from direct assay Ref.35. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: UniProtKB regulation of autophagy Inferred from direct assay Ref.35. Source: UniProtKB regulation of reactive oxygen species metabolic process Inferred from mutant phenotype Ref.33. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: UniProtKB aggresome Inferred from direct assay. Source: BHF-UCL cytosol Inferred from direct assay Ref.32Ref.35. Source: UniProtKB endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay Ref.35. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	PDZ domain binding Inferred from physical interaction. Source: BHF-UCL chaperone binding Inferred from physical interaction. Source: BHF-UCL protein kinase binding Inferred from physical interaction Ref.34. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction Ref.38. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.26Ref.33Ref.35Ref.37. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RANBP2	P49792	11	EBI-716346,EBI-973138
TRIP13	Q15645	3	EBI-716346,EBI-358993
ZNF746	Q6NUN9	6	EBI-716346,EBI-3862525

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60260-1)

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

Isoform 2 (identifier: O60260-2)

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

Isoform 3 (identifier: O60260-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     291-297: AGCPNSL → VCLLPGM
     298-465: Missing.

Isoform 4 (identifier: O60260-4)

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

Isoform 5 (identifier: O60260-5)

The sequence of this isoform differs from the canonical sequence as follows:
     290-290: V → VGTGDTVVLRGALGGFRRGV
     362-368: FAFCREC → YGQRRTK
     369-465: Missing.

Isoform 6 (identifier: O60260-6)

The sequence of this isoform differs from the canonical sequence as follows:
     58-206: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 465

465

E3 ubiquitin-protein ligase parkin

PRO_0000058576

Regions

Domain

1 – 76

76

Ubiquitin-like

Zinc finger

238 – 293

56

RING-type 1; atypical

Zinc finger

313 – 377

65

IBR-type

Zinc finger

418 – 449

32

RING-type 2

Region

204 – 238

35

SYT11 binding 1

Region

257 – 293

37

SYT11 binding 2

Natural variations

Alternative sequence

1 – 191

191

Missing in isoform 4.

VSP_011705

Alternative sequence

1 – 79

79

Missing in isoform 3.

VSP_011706

Alternative sequence

58 – 206

149

Missing in isoform 6.

VSP_041563

Alternative sequence

179 – 206

28

Missing in isoform 2.

VSP_011707

Alternative sequence

290

1

V → VGTGDTVVLRGALGGFRRGV in isoform 5.

VSP_011708

Alternative sequence

291 – 297

7

AGCPNSL → VCLLPGM in isoform 3.

VSP_011709

Alternative sequence

298 – 465

168

Missing in isoform 3.

VSP_011710

Alternative sequence

362 – 368

7

FAFCREC → YGQRRTK in isoform 5.

VSP_011711

Alternative sequence

369 – 465

97

Missing in isoform 5.

VSP_011712

Natural variant

15

1

V → M in PARK. Ref.56

VAR_019733

Natural variant

33

1

R → Q in PARK. Ref.59

VAR_019734

Natural variant

37

1

P → L in PARK2. Ref.54

VAR_019735

Natural variant

42

1

R → P in PARK; early-onset; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding. Ref.11 Ref.15 Ref.57

VAR_019736

Natural variant

46

1

A → P in PARK; early-onset; sporadic. Ref.58

VAR_019737

Natural variant

82

1

A → E in PARK2 and PARK. Ref.50 Ref.52 Ref.59
Corresponds to variant rs55774500 [ dbSNP | Ensembl ].

VAR_019738

Natural variant

92

1

A → V in PARK2.

VAR_019739

Natural variant

100

1

Q → H. Ref.61

VAR_019740

Natural variant

161

1

K → N in PARK2 and PARK; severely compromises the mitochondrial localization and fails to stabilize BCL2. Ref.35 Ref.44 Ref.48 Ref.62

VAR_019741

Natural variant

167

1

S → N. Ref.44 Ref.45 Ref.47 Ref.60
Corresponds to variant rs1801474 [ dbSNP | Ensembl ].

VAR_019742

Natural variant

192

1

M → L.
Corresponds to variant rs9456735 [ dbSNP | Ensembl ].

VAR_054107

Natural variant

192

1

M → V in PARK; early and late onset. Ref.57 Ref.60
Corresponds to variant rs9456735 [ dbSNP | Ensembl ].

VAR_019743

Natural variant

211

1

K → N in PARK; early and late onset; severely compromises the mitochondrial localization. Ref.48 Ref.55 Ref.60 Ref.62

VAR_019744

Natural variant

211

1

K → R in PARK; early onset. Ref.49

VAR_019745

Natural variant

212

1

C → Y in PARK2. Ref.51

VAR_019746

Natural variant

240

1

T → M in PARK; late onset. Ref.60

VAR_019747

Natural variant

240

1

T → R in PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization. Ref.11 Ref.14 Ref.15 Ref.35 Ref.42 Ref.62

VAR_019748

Natural variant

253

1

C → Y in PARK; late onset. Ref.59

VAR_019749

Natural variant

256

1

R → C in PARK2 and PARK; early and late onset; impairs the ability to ubiquitinate SNCAIP and ZNF746. Ref.14 Ref.44 Ref.48 Ref.52 Ref.57 Ref.59
Corresponds to variant rs34424986 [ dbSNP | Ensembl ].

VAR_019750

Natural variant

271

1

R → S. Ref.61

VAR_019751

Natural variant

275

1

R → W in PARK2 and PARK; early and late onset; impairs the ability to ubiquitinate SNCAIP. Ref.14 Ref.37 Ref.44 Ref.48 Ref.49 Ref.52 Ref.55 Ref.57 Ref.59
Corresponds to variant rs34424986 [ dbSNP | Ensembl ].

VAR_019752

Natural variant

280

1

D → N in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. Ref.48 Ref.59 Ref.62

VAR_019753

Natural variant

284

1

G → R in PARK2.

VAR_019754

Natural variant

289

1

C → G in PARK; fails to ubiquitinate SYT11; loses ability to bind SYT11. Ref.18 Ref.48
Corresponds to variant rs55961220 [ dbSNP | Ensembl ].

VAR_019755

Natural variant

311

1

Q → R in a patient with Parkinson disease; unknown pathological significance. Ref.2

VAR_062672

Natural variant

328

1

G → E in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. Ref.48 Ref.52 Ref.62

VAR_019756

Natural variant

334

1

R → C in PARK. Ref.48

VAR_019757

Natural variant

339

1

A → S. Ref.61

VAR_019758

Natural variant

351

1

T → P in PARK2; impairs folding of IBR domain. Ref.40 Ref.54

VAR_019759

Natural variant

366

1

R → W. Ref.47
Corresponds to variant rs56092260 [ dbSNP | Ensembl ].

VAR_019760

Natural variant

371

1

A → T in a patient with Parkinson disease; unknown pathological significance. Ref.2

VAR_062673

Natural variant

380

1

V → L. Ref.44 Ref.47 Ref.56 Ref.59
Corresponds to variant rs1801582 [ dbSNP | Ensembl ].

VAR_019761

Natural variant

394

1

D → N. Ref.44 Ref.56 Ref.59
Corresponds to variant rs1801334 [ dbSNP | Ensembl ].

VAR_019762

Natural variant

415

1

T → N in PARK2 and PARK; impairs the ability to ubiquitinate SNCAIP; does not affect turnover of CDCRE1; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria. Ref.14 Ref.36 Ref.44 Ref.48

VAR_019763

Natural variant

430

1

G → D in PARK; early onset; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria; impaired E3 ubiquitin-protein ligase toward ZNF746. Ref.36 Ref.37 Ref.48 Ref.49 Ref.55 Ref.57 Ref.59

VAR_019764

Natural variant

431

1

C → F in PARK2; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2. Ref.35 Ref.37 Ref.46

VAR_019765

Natural variant

437

1

P → L in PARK; early and late onset and impaired E3 ubiquitin-protein ligase toward BCL2. Ref.35 Ref.55 Ref.57 Ref.59 Ref.60

VAR_019766

Natural variant

441

1

C → R in PARK.

VAR_019767

Experimental info

Mutagenesis

332

1

C → S: Impairs folding of IBR domain. Ref.40

Mutagenesis

337

1

C → A: Impairs the ability to ubiquitinate SNCAIP. Ref.14

Mutagenesis

365

1

C → S: Impairs protein folding. Ref.40

Mutagenesis

418

1

C → R: Fails to ubiquitinate SYT11. Does not loose ability to bind SYT11. Ref.18

Mutagenesis

421

1

C → A: Impairs the ability of self-ubiquitination and to ubiquitinate SNCAIP. Ref.14 Ref.33

Mutagenesis

431

1

C → A: Impairs the ability to ubiquitinate SNCAIP. Ref.14

Sequence conflict

223

1

S → P in BAA25751. Ref.1

Sequence conflict

223

1

S → P in AAM21458. Ref.3

Sequence conflict

223

1

S → P in AAM21457. Ref.3

Sequence conflict

289 – 290

2

CV → MI in AAM21461. Ref.2

Sequence conflict

339

1

A → V in AAS88422. Ref.8

Secondary structure

1

.

.

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465

Helix Strand Turn

Details...

Beta strand

2 – 7

6

Turn

8 – 10

3

Beta strand

11 – 17

7

Beta strand

19 – 21

3

Helix

23 – 33

11

Beta strand

38 – 45

8

Beta strand

48 – 50

3

Turn

52 – 55

4

Helix

57 – 60

4

Beta strand

63 – 70

8

Beta strand

318 – 320

3

Beta strand

334 – 336

3

Beta strand

354 – 356

3

Turn

366 – 369

4

Beta strand

377 – 379

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 9A8BB802A3FC84C3	FASTA	465	51,641
	10 20 30 40 50 60 MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD 70 80 90 100 110 120 LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA 130 140 150 160 170 180 VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQGP 190 200 210 220 230 240 SCWDDVLIPN RMSGECQSPH CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT 250 260 270 280 290 300 CTDVRSPVLV FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE 310 320 330 340 350 360 LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV TCEGGNGLGC 370 380 390 400 410 420 GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ ARWEAASKET IKKTTKPCPR 430 440 450 460 CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG CEWNRVCMGD HWFDV
	Isoform 2 [UniParc]. Checksum: A435AF6495DED559	FASTA	437	48,713
	10 20 30 40 50 60 MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD 70 80 90 100 110 120 LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA 130 140 150 160 170 180 VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQEF 190 200 210 220 230 240 FFKCGAHPTS DKETSVALHL IATNSRNITC ITCTDVRSPV LVFQCNSRHV ICLDCFHLYC 250 260 270 280 290 300 VTRLNDRQFV HDPQLGYSLP CVAGCPNSLI KELHHFRILG EEQYNRYQQY GAEECVLQMG 310 320 330 340 350 360 GVLCPRPGCG AGLLPEPDQR KVTCEGGNGL GCGFAFCREC KEAYHEGECS AVFEASGTTT 370 380 390 400 410 420 QAYRVDERAA EQARWEAASK ETIKKTTKPC PRCHVPVEKN GGCMHMKCPQ PQCRLEWCWN 430 CGCEWNRVCM GDHWFDV
	Isoform 3 [UniParc]. Checksum: 4CB1B7EBD8A25F4B	FASTA	218	23,639
	10 20 30 40 50 60 MNATGGDDPR NAAGGCEREP QSLTRVDLSS SVLPGDSVGL AVILHTDSRK DSPPAGSPAG 70 80 90 100 110 120 RSIYNSFYVY CKGPCQRVQP GKLRVQCSTC RQATLTLTQG PSCWDDVLIP NRMSGECQSP 130 140 150 160 170 180 HCPGTSAEFF FKCGAHPTSD KETSVALHLI ATNSRNITCI TCTDVRSPVL VFQCNSRHVI 190 200 210 CLDCFHLYCV TRLNDRQFVH DPQLGYSLPC VVCLLPGM
	Isoform 4 [UniParc]. Checksum: CAE5D2F530395FA1	FASTA	274	30,616
	10 20 30 40 50 60 MSGECQSPHC PGTSAEFFFK CGAHPTSDKE TSVALHLIAT NSRNITCITC TDVRSPVLVF 70 80 90 100 110 120 QCNSRHVICL DCFHLYCVTR LNDRQFVHDP QLGYSLPCVA GCPNSLIKEL HHFRILGEEQ 130 140 150 160 170 180 YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL LPEPDQRKVT CEGGNGLGCG FAFCRECKEA 190 200 210 220 230 240 YHEGECSAVF EASGTTTQAY RVDERAAEQA RWEAASKETI KKTTKPCPRC HVPVEKNGGC 250 260 270 MHMKCPQPQC RLEWCWNCGC EWNRVCMGDH WFDV
	Isoform 5 [UniParc]. Checksum: 48C0F41C86226606	FASTA	387	42,407
	10 20 30 40 50 60 MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD 70 80 90 100 110 120 LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA 130 140 150 160 170 180 VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQGP 190 200 210 220 230 240 SCWDDVLIPN RMSGECQSPH CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT 250 260 270 280 290 300 CTDVRSPVLV FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV GTGDTVVLRG 310 320 330 340 350 360 ALGGFRRGVA GCPNSLIKEL HHFRILGEEQ YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL 370 380 LPEPDQRKVT CEGGNGLGCG YGQRRTK
	Isoform 6 [UniParc]. Checksum: 4AE7F62C46499A24	FASTA	316	35,631
	10 20 30 40 50 60 MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQEFF 70 80 90 100 110 120 FKCGAHPTSD KETSVALHLI ATNSRNITCI TCTDVRSPVL VFQCNSRHVI CLDCFHLYCV 130 140 150 160 170 180 TRLNDRQFVH DPQLGYSLPC VAGCPNSLIK ELHHFRILGE EQYNRYQQYG AEECVLQMGG 190 200 210 220 230 240 VLCPRPGCGA GLLPEPDQRK VTCEGGNGLG CGFAFCRECK EAYHEGECSA VFEASGTTTQ 250 260 270 280 290 300 AYRVDERAAE QARWEAASKE TIKKTTKPCP RCHVPVEKNG GCMHMKCPQP QCRLEWCWNC 310 GCEWNRVCMG DHWFDV

References

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[1]	"Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism." Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Nature 392:605-608(1998) [PubMed: 9560156] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN PARK2. Tissue: Fetal brain and Skeletal muscle.
[2]	"Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood." Kasap M., Akpinar G., Sazci A., Idrisoglu H.A., Vahaboglu H. Neurosci. Lett. 460:196-200(2009) [PubMed: 19501131] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS ARG-311 AND THR-371, MASS SPECTROMETRY.
[3]	"Functional and molecular diversity of parkin." D'Agata V., Scapagnini G., Cavallaro S. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Testis.
[8]	Zou H.Q., Chan P. Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 312-361.
[9]	"Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients." Shimura H., Hattori N., Kubo S., Yoshikawa M., Kitada T., Matsumine H., Asakawa S., Minoshima S., Yamamura Y., Shimizu N., Mizuno Y. Ann. Neurol. 45:668-672(1999) [PubMed: 10319893] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity." Imai Y., Soda M., Takahashi R. J. Biol. Chem. 275:35661-35664(2000) [PubMed: 10973942] [Abstract] Cited for: FUNCTION IN UBIQUITINATION.
[11]	"Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase." Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T. Nat. Genet. 25:302-305(2000) [PubMed: 10888878] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK PRO-42 AND ARG-240.
[12]	"Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1." Zhang Y., Gao J., Chung K.K.K., Huang H., Dawson V.L., Dawson T.M. Proc. Natl. Acad. Sci. U.S.A. 97:13354-13359(2000) [PubMed: 11078524] [Abstract] Cited for: INTERACTION WITH UBE2L6 AND SEPT5, UBIQUITINATION OF SEPT5.
[13]	"An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin." Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., Takahashi R. Cell 105:891-902(2001) [PubMed: 11439185] [Abstract] Cited for: UBIQUITINATION OF GPR37.
[14]	"Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease." Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A., Dawson V.L., Dawson T.M. Nat. Med. 7:1144-1150(2001) [PubMed: 11590439] [Abstract] Cited for: INTERACTION, UBIQUITINATION OF SNCAIP, CHARACTERIZATION OF VARIANTS PARK2 ARG-240; CYS-256; TRP-275 AND ASN-415, MUTAGENESIS OF CYS-337; CYS-421 AND CYS-431.
[15]	"Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease." Shimura H., Schlossmacher M.G., Hattori N., Frosch M.P., Trockenbacher A., Schneider R., Mizuno Y., Kosik K.S., Selkoe D.J. Science 293:263-269(2001) [PubMed: 11431533] [Abstract] Cited for: UBIQUITINATION OF AN O-GLYCOSYLATED ISOFORM OF SNCAIP, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK PRO-42 AND ARG-240.
[16]	"Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily." Marin I., Ferrus A. Mol. Biol. Evol. 19:2039-2050(2002) [PubMed: 12446796] [Abstract] Cited for: PRESENCE OF ATYPICAL RING FINGER DOMAINS.
[17]	"CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity." Imai Y., Soda M., Hatakeyama S., Akagi T., Hashikawa T., Nakayama K., Takahashi R. Mol. Cell 10:55-67(2002) [PubMed: 12150907] [Abstract] Cited for: INTERACTION WITH STUB1 AND HSP70, UBIQUITINATION OF STUB1.
[18]	"The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI." Huynh D.P., Scoles D.R., Nguyen D., Pulst S.M. Hum. Mol. Genet. 12:2587-2597(2003) [PubMed: 12925569] [Abstract] Cited for: INTERACTION WITH SYT11, CHARACTERIZATION OF VARIANT PARK GLY-289, MUTAGENESIS OF CYS-418.
[19]	"A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death." Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R. J. Biol. Chem. 278:51901-51910(2003) [PubMed: 14532270] [Abstract] Cited for: INTERACTION WITH PACRG.
[20]	"Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity." Staropoli J.F., McDermott C., Martinat C., Schulman B., Demireva E., Abeliovich A. Neuron 37:735-749(2003) [PubMed: 12628165] [Abstract] Cited for: FUNCTION, INTERACTION WITH FBXW7 AND CUL1, UBIQUITINATION OF CYCLIN E.
[21]	"Alterations in the common fragile site gene Parkin in ovarian and other cancers." Denison S.R., Wang F., Becker N.A., Schuele B., Kock N., Phillips L.A., Klein C., Smith D.I. Oncogene 22:8370-8378(2003) [PubMed: 14614460] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[22]	"Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27." 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. Proc. Natl. Acad. Sci. U.S.A. 100:5956-5961(2003) [PubMed: 12719539] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN CANCER.
[23]	"How does parkin ligate ubiquitin to Parkinson's disease?" Kahle P.J., Haass C. EMBO Rep. 5:681-685(2004) [PubMed: 15229644] [Abstract] Cited for: REVIEW.
[24]	"S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function." Chung K.K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L., Dawson V.L., Dawson T.M. Science 304:1328-1331(2004) [PubMed: 15105460] [Abstract] Cited for: FUNCTION, UBIQUITINATION, S-NITROSYLATION.
[25]	"Parkin interacts with the proteasome subunit alpha4." Dachsel J.C., Lucking C.B., Deeg S., Schultz E., Lalowski M., Casademunt E., Corti O., Hampe C., Patenge N., Vaupel K., Yamamoto A., Dichgans M., Brice A., Wanker E.E., Kahle P.J., Gasser T. FEBS Lett. 579:3913-3919(2005) [PubMed: 15987638] [Abstract] Cited for: INTERACTION WITH PSMA7.
[26]	"Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation." 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. J. Neurosci. 25:2002-2009(2005) [PubMed: 15728840] [Abstract] Cited for: FUNCTION, INTERACTION WITH SNCAIP.
[27]	"Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death." 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. J. Neurosci. 25:7968-7978(2005) [PubMed: 16135753] [Abstract] Cited for: FUNCTION, INTERACTION WITH AIMP2.
[28]	"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration." Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A. Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed: 16352719] [Abstract] Cited for: INTERACTION WITH LRRK2.
[29]	"Parkin ubiquitinates and promotes the degradation of RanBP2." Um J.W., Min D.S., Rhim H., Kim J., Paik S.R., Chung K.C. J. Biol. Chem. 281:3595-3603(2006) [PubMed: 16332688] [Abstract] Cited for: INTERACTION WITH RANBP2.
[30]	"Functional modulation of parkin through physical interaction with SUMO-1." Um J.W., Chung K.C. J. Neurosci. Res. 84:1543-1554(2006) [PubMed: 16955485] [Abstract] Cited for: INTERACTION WITH SUMO1, SUBCELLULAR LOCATION.
[31]	"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6." Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S. J. Cell Biol. 178:1025-1038(2007) [PubMed: 17846173] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[32]	"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy." Narendra D., Tanaka A., Suen D.F., Youle R.J. J. Cell Biol. 183:795-803(2008) [PubMed: 19029340] [Abstract] Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION.
[33]	"Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress." Yu F., Zhou J. Neurosci. Lett. 440:4-8(2008) [PubMed: 18541373] [Abstract] Cited for: INTERACTION WITH RNF41, UBIQUITINATION, MUTAGENESIS OF CYS-421, FUNCTION.
[34]	"The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations." Geisler S., Holmstrom K.M., Treis A., Skujat D., Weber S.S., Fiesel F.C., Kahle P.J., Springer W. Autophagy 6:871-878(2010) [PubMed: 20798600] [Abstract] Cited for: INTERACTION WITH PINK1.
[35]	"Parkin mono-ubiquitinates Bcl-2 and regulates autophagy." Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G. J. Biol. Chem. 285:38214-38223(2010) [PubMed: 20889974] [Abstract] Cited for: FUNCTION, INTERACTION WITH BCL2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240 AND PHE-431, CHARACTERIZATION OF VARIANT PARK LEU-437.
[36]	"PINK1-dependent recruitment of Parkin to mitochondria in mitophagy." 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. Proc. Natl. Acad. Sci. U.S.A. 107:378-383(2010) [PubMed: 19966284] [Abstract] Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH PINK1, CHARACTERIZATION OF VARIANTS PARK ASN-415 AND ASP-430.
[37]	"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease." Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O., Troconso J.C., Dawson V.L., Dawson T.M. Cell 144:689-702(2011) [PubMed: 21376232] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZNF746, CHARACTERIZATION OF VARIANTS PARK TRP-275; ASP-430 AND PHE-431.
[38]	"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids." Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E. Nature 474:105-108(2011) [PubMed: 21532592] [Abstract] Cited for: FUNCTION, REACTION MECHANISM, INTERACTION WITH UBE2L3.
[39]	"Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain." Sakata E., Yamaguchi Y., Kurimoto E., Kikuchi J., Yokoyama S., Yamada S., Kawahara H., Yokosawa H., Hattori N., Mizuno Y., Tanaka K., Kato K. EMBO Rep. 4:301-306(2003) [PubMed: 12634850] [Abstract] Cited for: STRUCTURE BY NMR OF 1-76, INTERACTION WITH PSMD4.
[40]	"Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease." Beasley S.A., Hristova V.A., Shaw G.S. Proc. Natl. Acad. Sci. U.S.A. 104:3095-3100(2007) [PubMed: 17360614] [Abstract] Cited for: STRUCTURE BY NMR OF 307-384 IN COMPLEX WITH ZINC IONS, CHARACTERIZATION OF VARIANT PARK2 PRO-351, MUTAGENESIS OF CYS-332 AND CYS-365, MASS SPECTROMETRY.
[41]	"Parkin genetics: one model for Parkinson's disease." Mata I.F., Lockhart P.J., Farrer M.J. Hum. Mol. Genet. 13:R127-R133(2004) [PubMed: 14976155] [Abstract] Cited for: REVIEW ON VARIANTS.
[42]	"Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene." Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B., Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A., Minoshima S., Shimizu N., Mizuno Y. Biochem. Biophys. Res. Commun. 249:754-758(1998) [PubMed: 9731209] [Abstract] Cited for: VARIANT PARK2 ARG-240.
[43]	Erratum Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B., Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A., Minoshima S., Shimizu N., Mizuno Y. Biochem. Biophys. Res. Commun. 251:666-666(1998)
[44]	"A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe." Abbas N., Luecking C.B., Ricard S., Duerr A., Bonifati V., De Michele G., Bouley S., Vaughan J.R., Gasser T., Marconi R., Broussolle E., Brefel-Courbon C., Harhangi B.S., Oostra B.A., Fabrizio E., Bohme G.A., Pradier L., Wood N.W. , Filla A., Meco G., Denefle P., Agid Y., Brice A. Hum. Mol. Genet. 8:567-574(1999) [PubMed: 10072423] [Abstract] Cited for: VARIANTS PARK2 ASN-161; CYS-256; TRP-275 AND ASN-415, VARIANTS ASN-167; LEU-380 AND ASN-394.
[45]	"Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson's disease." Satoh J., Kuroda Y. NeuroReport 10:2735-2739(1999) [PubMed: 10511432] [Abstract] Cited for: VARIANT ASN-167.
[46]	"Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism." Maruyama M., Ikeuchi T., Saito M., Ishikawa A., Yuasa T., Tanaka H., Hayashi S., Wakabayashi K., Takahashi H., Tsuji S. Ann. Neurol. 48:245-250(2000) [PubMed: 10939576] [Abstract] Cited for: VARIANT PARK2 PHE-431.
[47]	"Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in Taiwan." Hu C.-J., Sung S.-M., Liu H.-C., Lee C.-C., Tsai C.-H., Chang J.-G. Eur. Neurol. 44:90-93(2000) [PubMed: 10965160] [Abstract] Cited for: VARIANTS ASN-167; TRP-366 AND LEU-380.
[48]	"Association between early-onset Parkinson's disease and mutations in the parkin gene." Luecking C.B., Duerr A., Bonifati V., Vaughan J.R., De Michele G., Gasser T., Harhangi B.S., Meco G., Denefle P., Wood N.W., Agid Y., Brice A. N. Engl. J. Med. 342:1560-1567(2000) [PubMed: 10824074] [Abstract] Cited for: VARIANTS PARK ASN-161; ASN-211; CYS-256; TRP-275; ASN-280; GLY-289; GLU-328; CYS-334; ASN-415 AND ASP-430.
[49]	"Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects." Periquet M., Luecking C.B., Vaughan J.R., Bonifati V., Duerr A., De Michele G., Horstink M., Farrer M., Illarioshkin S.N., Pollak P., Borg M., Brefel-Courbon C., Denefle P., Meco G., Gasser T., Breteler M.M., Wood N.W., Agid Y., Brice A. Am. J. Hum. Genet. 68:617-626(2001) [PubMed: 11179010] [Abstract] Cited for: VARIANTS PARK ARG-211; TRP-275 AND ASP-430.
[50]	"The importance of gene dosage studies: mutational analysis of the parkin gene in early-onset parkinsonism." Hedrich K., Kann M., Lanthaler A.J., Dalski A., Eskelson C., Landt O., Schwinger E., Vieregge P., Lang A.E., Breakefield X.O., Ozelius L.J., Pramstaller P.P., Klein C. Hum. Mol. Genet. 10:1649-1656(2001) [PubMed: 11487568] [Abstract] Cited for: VARIANT PARK2 GLU-82.
[51]	"A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile parkinsonism in a population from North West Colombia." Pineda-Trujillo N., Carvajal-Carmona L.G., Buritica O., Moreno S., Uribe C., Pineda D., Toro M., Garcia F., Arias W., Bedoya G., Lopera F., Ruiz-Linares A. Neurosci. Lett. 298:87-90(2001) [PubMed: 11163284] [Abstract] Cited for: VARIANT PARK2 TYR-212.
[52]	"Complex relationship between parkin mutations and Parkinson disease." French Parkinson's disease genetics study group, European consortium on genetic susceptibility on Parkinson's disease West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V., Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A., Wood N.W., Duerr A., Hardy J., Brice A., Farrer M. Am. J. Med. Genet. 114:584-591(2002) [PubMed: 12116199] [Abstract] Cited for: VARIANTS PARK GLU-82; CYS-256; TRP-275; GLU-328 AND 441-ARG.
[53]	Erratum French Parkinson's disease genetics study group, European consortium on genetic susceptibility on Parkinson's disease West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V., Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A., Wood N.W., Duerr A., Hardy J., Brice A., Farrer M.J. Am. J. Med. Genet. 114:992-992(2002)
[54]	"Role of parkin mutations in 111 community-based patients with early-onset parkinsonism." Kann M., Jacobs H., Mohrmann K., Schumacher K., Hedrich K., Garrels J., Wiegers K., Schwinger E., Pramstaller P.P., Breakefield X.O., Ozelius L.J., Vieregge P., Klein C. Ann. Neurol. 51:621-625(2002) [PubMed: 12112109] [Abstract] Cited for: VARIANTS PARK2 LEU-37 AND PRO-351.
[55]	"Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families." Nichols W.C., Pankratz N., Uniacke S.K., Pauciulo M.W., Halter C., Rudolph A., Conneally P.M., Foroud T. J. Med. Genet. 39:489-492(2002) [PubMed: 12114481] [Abstract] Cited for: VARIANTS PARK ASN-211; TRP-275; ASP-430 AND LEU-437.
[56]	"Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism." Munoz E., Tolosa E., Pastor P., Marti M.J., Valldeoriola F., Campdelacreu J., Oliva R. J. Neurol. Neurosurg. Psych. 73:582-584(2002) [PubMed: 12397156] [Abstract] Cited for: VARIANT PARK MET-15, VARIANTS LEU-380 AND ASN-394.
[57]	"Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations." Hedrich K., Marder K., Harris J., Kann M., Lynch T., Meija-Santana H., Pramstaller P.P., Schwinger E., Bressman S.B., Fahn S., Klein C. Neurology 58:1239-1246(2002) [PubMed: 11971093] [Abstract] Cited for: VARIANTS PARK PRO-42; VAL-192; CYS-256; TRP-275; ASP-430 AND LEU-437.
[58]	"A new point mutation on exon 2 of parkin gene in Parkinson's disease." Xu Y., Liu Z., Wang Y., Tao E., Chen G., Chen B. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:409-411(2002) [PubMed: 12362318] [Abstract] Cited for: VARIANT PARK PRO-46.
[59]	"Parkin mutations and susceptibility alleles in late-onset Parkinson's disease." Oliveira S.A., Scott W.K., Martin E.R., Nance M.A., Watts R.L., Hubble J.P., Koller W.C., Pahwa R., Stern M.B., Hiner B.C., Ondo W.G., Allen F.H. Jr., Scott B.L., Goetz C.G., Small G.W., Mastaglia F., Stajich J.M., Zhang F. , Booze M.W., Winn M.P., Middleton L.T., Haines J.L., Pericak-Vance M.A., Vance J.M. Ann. Neurol. 53:624-629(2003) [PubMed: 12730996] [Abstract] Cited for: VARIANTS PARK GLN-33; TYR-253; CYS-256; TRP-275; ASN-280; ASP-430 AND LEU-437, VARIANTS GLU-82; LEU-380 AND ASN-394.
[60]	"Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease." Foroud T., Uniacke S.K., Liu L., Pankratz N., Rudolph A., Halter C., Shults C., Marder K., Conneally P.M., Nichols W.C. Neurology 60:796-801(2003) [PubMed: 12629236] [Abstract] Cited for: VARIANTS PARK VAL-192; ASN-211; MET-240 AND LEU-437, VARIANT ASN-167.
[61]	"Parkin mutations are rare in patients with young-onset parkinsonism in a US population." Chen R., Gosavi N.S., Langston J.W., Chan P. Parkinsonism Relat. Disord. 9:309-312(2003) [PubMed: 12781599] [Abstract] Cited for: VARIANTS HIS-100; SER-271 AND SER-339.
[62]	"PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy." Matsuda N., Sato S., Shiba K., Okatsu K., Saisho K., Gautier C.A., Sou Y.S., Saiki S., Kawajiri S., Sato F., Kimura M., Komatsu M., Hattori N., Tanaka K. J. Cell Biol. 189:211-221(2010) [PubMed: 20404107] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PARK ASN-161; ASN-211; ARG-240; ASN-280 AND GLU-328.
+	Additional computationally mapped references.

Web resources

GeneReviews

Protein Spotlight

Life's tremors - Issue 131 of September 2011

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB009973 mRNA. Translation: BAA25751.1.
EF375726 mRNA. Translation: ABN46990.1.
AF381282 mRNA. Translation: AAM21457.1.
AF381283 mRNA. Translation: AAM21458.1.
AF381286 mRNA. Translation: AAM21461.1.
AK292590 mRNA. Translation: BAF85279.1.
AL445215 , AL035697, AL132982, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAH73681.1.
AL035697 , AL132982, AL445215, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAI21385.1.
AL132982 , AL035697, AL445215, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAI23601.1.
CH471051 Genomic DNA. Translation: EAW47573.1.
BC022014 mRNA. Translation: AAH22014.1.
AY564225 Genomic DNA. Translation: AAS88422.1.

IPI

IPI00005254.
IPI00332282.
IPI00332283.
IPI00470428.
IPI00470429.
IPI00984693.

RefSeq

NP_004553.2. NM_004562.2.
NP_054642.2. NM_013987.2.
NP_054643.2. NM_013988.2.

UniGene

Hs.132954.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IYF	NMR	-	A	1-76	[»]
2JMO	NMR	-	A	308-384	[»]

ProteinModelPortal

O60260.

SMR

O60260. Positions 1-76, 307-384, 410-464.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37655N.

IntAct

O60260. 9 interactions.

MINT

MINT-1351124.

STRING

O60260.

PTM databases

PhosphoSite

O60260.

Proteomic databases

PRIDE

O60260.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366898; ENSP00000355865; ENSG00000185345.

GeneID

5071.

KEGG

hsa:5071.

UCSC

uc003qtx.2. human.
uc010kke.1. human.

Organism-specific databases

CTD

5071.

GeneCards

GC06M161740.

HGNC

HGNC:8607. PARK2.

HPA

CAB016257.

MIM

168600. phenotype.
600116. phenotype.
602544. gene.

neXtProt

NX_O60260.

Orphanet

2828. Young adult-onset Parkinsonism.

PharmGKB

PA32942.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG053682.

InParanoid

O60260.

OMA

CTDVRSP.

OrthoDB

EOG4HHP2G.

PhylomeDB

O60260.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O60260.

Bgee

O60260.

CleanEx

HS_PARK2.

Genevestigator

O60260.

GermOnline

ENSG00000185345. Homo sapiens.

Family and domain databases

InterPro

IPR003977. Parkin.
IPR000626. Ubiquitin.
IPR019955. Ubiquitin_supergroup.
IPR002867. Znf_C6HC.
[Graphical view]

KO

K04556.

PANTHER

PTHR11685:SF2. Parkin. 1 hit.

Pfam

PF01485. IBR. 2 hits.
PF00240. ubiquitin. 1 hit.
[Graphical view]

PIRSF

PIRSF037880. Parkin. 1 hit.

PRINTS

PR01475. PARKIN.

SMART

SM00647. IBR. 2 hits.
SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS00299. UBIQUITIN_1. False negative.
PS50053. UBIQUITIN_2. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

19538.

SOURCE

Search...

Entry information

Entry name

PRKN2_HUMAN

Accession

Primary (citable) accession number: O60260
Secondary accession number(s): A3FG77 , A8K975, Q5TFV8, Q6Q2I6, Q8NI41, Q8NI43, Q8NI44, Q8WW07

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.