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Q9BXM7 (PINK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase PINK1, mitochondrial

EC=2.7.11.1
Alternative name(s):
BRPK
PTEN-induced putative kinase protein 1
Gene names
Name:PINK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length581 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protects against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Targets PARK2 to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Ref.2 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.18

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium. Ref.2

Subunit structure

Interacts with PARK2. Interacts with FBXO7. Ref.7 Ref.9 Ref.11

Subcellular location

Mitochondrion outer membrane; Single-pass membrane protein. Cytoplasmcytosol Ref.6 Ref.7 Ref.11 Ref.18.

Tissue specificity

Highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. Present in the embryonic testis from an early stage of development. Ref.1

Post-translational modification

Autophosphorylation at Ser-228 and Ser-402 is essential for Parkin/PARK2 recruitment to depolarized mitochondria.

Involvement in disease

Parkinson disease 6 (PARK6) [MIM:605909]: A neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.33 Ref.34

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAutophagy
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
   DomainTransit peptide
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to toxic substance

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from direct assay Ref.2. Source: UniProtKB

mitochondrion degradation

Inferred from mutant phenotype Ref.7Ref.11. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

positive regulation of dopamine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of release of cytochrome c from mitochondria

Inferred from mutant phenotype PubMed 19880420. Source: BHF-UCL

positive regulation of synaptic transmission, dopaminergic

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

protein ubiquitination

Inferred from mutant phenotype Ref.11. Source: UniProtKB

regulation of protein complex assembly

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

regulation of protein ubiquitination

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

response to stress

Inferred from direct assay Ref.18. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay Ref.7. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay Ref.18Ref.7Ref.11. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.2. Source: UniProtKB

C3HC4-type RING finger domain binding

Inferred from physical interaction PubMed 19880420. Source: BHF-UCL

calcium-dependent protein kinase activity

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

kinase activity

Inferred from direct assay PubMed 15824318. Source: MGI

magnesium ion binding

Inferred from direct assay Ref.2. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.2 (identifier: Q9BXM7-1)

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: Q9BXM7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-307: Missing.
     308-320: LGHGRTLFLVMKN → MCGSQRPSPLSTS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 7777Mitochondrion Potential
Chain78 – 581504Serine/threonine-protein kinase PINK1, mitochondrial
PRO_0000024369

Regions

Topological domain78 – 9316Mitochondrial intermembrane Potential
Transmembrane94 – 11017Helical; Potential
Topological domain111 – 581471Cytoplasmic Potential
Domain156 – 511356Protein kinase
Nucleotide binding162 – 1709ATP By similarity UniProtKB Q02750

Sites

Active site3621Proton acceptor By similarity UniProtKB Q02750
Binding site1861ATP By similarity

Amino acid modifications

Modified residue2281Phosphoserine; by autocatalysis Ref.10
Modified residue4021Phosphoserine; by autocatalysis Ref.10

Natural variations

Alternative sequence1 – 307307Missing in isoform 2.
VSP_050754
Alternative sequence308 – 32013LGHGR…LVMKN → MCGSQRPSPLSTS in isoform 2.
VSP_050755
Natural variant671L → F. Ref.32
VAR_046566
Natural variant681R → P. Ref.32
VAR_046567
Natural variant921C → F in PARK6. Ref.13
VAR_046568
Natural variant981R → W. Ref.32
VAR_046569
Natural variant1111I → S. Ref.32
VAR_046570
Natural variant1151Q → L. Ref.20 Ref.23
Corresponds to variant rs148871409 [ dbSNP | Ensembl ].
VAR_046571
Natural variant1241A → V. Ref.32
VAR_046572
Natural variant1251C → G in PARK6. Ref.27
VAR_062773
Natural variant1261Q → P in PARK6; strongly reduces interaction with PARK2. Ref.7 Ref.33
VAR_064344
Natural variant1451T → M. Ref.32
Corresponds to variant rs45604240 [ dbSNP | Ensembl ].
VAR_046573
Natural variant1471R → H in PARK6; unknown pathological significance. Ref.17
VAR_046574
Natural variant1481L → W. Ref.31
Corresponds to variant rs56297806 [ dbSNP | Ensembl ].
VAR_041010
Natural variant1681A → P in PARK6; has reduced autophosphorylation activity compared to wild-type; localizes to the mitochondria and immunogold experiments reveal that both wild-type and mutant proteins face the mitochondrial intermembrane space. Ref.13 Ref.21 Ref.23
VAR_046575
Natural variant1861K → N. Ref.32
VAR_046576
Natural variant1961P → L in PARK6. Ref.23
VAR_046577
Natural variant1961P → S. Ref.31
Corresponds to variant rs35802484 [ dbSNP | Ensembl ].
VAR_041011
Natural variant2091P → L. Ref.31
Corresponds to variant rs34677717 [ dbSNP | Ensembl ].
VAR_041012
Natural variant2151P → L in a glioblastoma multiforme sample; somatic mutation. Ref.31
VAR_041013
Natural variant2171A → D in PARK6. Ref.25
VAR_046578
Natural variant2311E → G. Ref.16
VAR_046579
Natural variant2351N → I. Ref.16
VAR_046580
Natural variant2401E → K in PARK6. Ref.16 Ref.27
VAR_046581
Natural variant2571T → I. Ref.32
VAR_046582
Natural variant2631R → G. Ref.16
VAR_046583
Natural variant2681L → V in PARK6. Ref.19 Ref.32
VAR_046584
Natural variant2711H → Q in PARK6. Ref.14
VAR_046585
Natural variant2761R → Q. Ref.32
VAR_046586
Natural variant2791R → H in PARK6. Ref.20
VAR_046587
Natural variant2801A → T in PARK6; early-onset. Ref.29
VAR_062774
Natural variant2961P → L. Ref.13 Ref.32
VAR_046588
Natural variant3051P → L.
Corresponds to variant rs7349186 [ dbSNP | Ensembl ].
VAR_018993
Natural variant3091G → D in PARK6; fails to maintain mitochondrial membrane potential; has reduced autophosphorylation activity compared to wild-type; strongly reduces interaction with PARK2. Ref.7 Ref.18 Ref.21
VAR_018994
Natural variant3131T → M in PARK6. Ref.26
VAR_046589
Natural variant3171V → I. Ref.24 Ref.32
Corresponds to variant rs200949139 [ dbSNP | Ensembl ].
VAR_046590
Natural variant3181M → L. Ref.16
VAR_046591
Natural variant3221P → L. Ref.32
VAR_046592
Natural variant3391A → T. Ref.16 Ref.24 Ref.31 Ref.32
Corresponds to variant rs55831733 [ dbSNP | Ensembl ].
VAR_041014
Natural variant3401A → T. Ref.3 Ref.13 Ref.16 Ref.23 Ref.29 Ref.30 Ref.31
Corresponds to variant rs3738136 [ dbSNP | Ensembl ].
VAR_018995
Natural variant3411M → I. Ref.31
Corresponds to variant rs35813094 [ dbSNP | Ensembl ].
VAR_041015
Natural variant3471L → P in PARK6; strongly reduces interaction with PARK2. Ref.7 Ref.14 Ref.16 Ref.34
VAR_046593
Natural variant3621D → H. Ref.16
VAR_046594
Natural variant3691L → P in PARK6. Ref.27
VAR_062775
Natural variant3771C → F. Ref.31
Corresponds to variant rs34203620 [ dbSNP | Ensembl ].
VAR_041016
Natural variant3831A → T. Ref.24 Ref.32
Corresponds to variant rs45515602 [ dbSNP | Ensembl ].
VAR_046595
Natural variant3861G → A in PARK6. Ref.27
VAR_062776
Natural variant3881C → R in PARK6. Ref.22
VAR_046596
Natural variant3951G → V. Ref.32
VAR_046597
Natural variant3991P → L in PARK6; digenic inheritance; associated with Ser-39 mutation in PARK7 gene. Ref.28
VAR_062777
Natural variant4071R → Q in PARK6; early-onset. Ref.30
VAR_062778
Natural variant4091G → V in PARK6. Ref.27
VAR_062779
Natural variant4111G → S. Ref.24
Corresponds to variant rs45478900 [ dbSNP | Ensembl ].
VAR_046598
Natural variant4171E → G in PARK6. Ref.14
VAR_046599
Natural variant4251P → S. Ref.16
VAR_046600
Natural variant4311Y → H May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.24
VAR_046601
Natural variant4421I → T. Ref.13 Ref.32
VAR_046602
Natural variant4511N → S May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.24
VAR_046603
Natural variant4611L → S. Ref.24
VAR_046604
Natural variant4641R → H in PARK6. Ref.13
VAR_046605
Natural variant4761E → K May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.13 Ref.16 Ref.23 Ref.24 Ref.32
Corresponds to variant rs115477764 [ dbSNP | Ensembl ].
VAR_046606
Natural variant4771S → T. Ref.31
Corresponds to variant rs34416410 [ dbSNP | Ensembl ].
VAR_041017
Natural variant4891L → P in PARK6. Ref.16
VAR_046607
Natural variant5011R → P May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.24
VAR_046608
Natural variant5211N → T. Ref.3 Ref.13 Ref.16 Ref.23 Ref.29 Ref.30 Ref.31
Corresponds to variant rs1043424 [ dbSNP | Ensembl ].
VAR_018996
Natural variant5251D → N. Ref.13 Ref.32
VAR_046609
Natural variant5341Q → QQ in PARK6. Ref.20
VAR_046610
Natural variant5371A → T. Ref.32
VAR_046611
Natural variant5751C → R May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.24
VAR_046612

Experimental info

Mutagenesis2191K → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-362 and ALA-384. Ref.12
Mutagenesis3621D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-384. Ref.12
Mutagenesis3841D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-362. Ref.12
Sequence conflict2091P → A in AAH28215. Ref.5
Sequence conflict4191S → P in BAC11484. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 721FE01F63263A64

FASTA58162,769
        10         20         30         40         50         60 
MAVRQALGRG LQLGRALLLR FTGKPGRAYG LGRPGPAAGC VRGERPGWAA GPGAEPRRVG 

        70         80         90        100        110        120 
LGLPNRLRFF RQSVAGLAAR LQRQFVVRAW GCAGPCGRAV FLAFGLGLGL IEEKQAESRR 

       130        140        150        160        170        180 
AVSACQEIQA IFTQKSKPGP DPLDTRRLQG FRLEEYLIGQ SIGKGCSAAV YEATMPTLPQ 

       190        200        210        220        230        240 
NLEVTKSTGL LPGRGPGTSA PGEGQERAPG APAFPLAIKM MWNISAGSSS EAILNTMSQE 

       250        260        270        280        290        300 
LVPASRVALA GEYGAVTYRK SKRGPKQLAP HPNIIRVLRA FTSSVPLLPG ALVDYPDVLP 

       310        320        330        340        350        360 
SRLHPEGLGH GRTLFLVMKN YPCTLRQYLC VNTPSPRLAA MMLLQLLEGV DHLVQQGIAH 

       370        380        390        400        410        420 
RDLKSDNILV ELDPDGCPWL VIADFGCCLA DESIGLQLPF SSWYVDRGGN GCLMAPEVST 

       430        440        450        460        470        480 
ARPGPRAVID YSKADAWAVG AIAYEIFGLV NPFYGQGKAH LESRSYQEAQ LPALPESVPP 

       490        500        510        520        530        540 
DVRQLVRALL QREASKRPSA RVAANVLHLS LWGEHILALK NLKLDKMVGW LLQQSAATLL 

       550        560        570        580 
ANRLTEKCCV ETKMKMLFLA NLECETLCQA ALLLCSWRAA L 

« Hide

Isoform 2 [UniParc].

Checksum: C54C628F879B4BED
Show »

FASTA27430,104

References

« Hide 'large scale' references
[1]"Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway."
Unoki M., Nakamura Y.
Oncogene 20:4457-4465(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Endometrium.
[2]"BRPK, a novel protein kinase showing increased expression in mouse cancer cell lines with higher metastatic potential."
Nakajima A., Kataoka K., Hong M., Sakaguchi M., Huh N.-H.
Cancer Lett. 201:195-201(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AUTOPHOSPHORYLATION.
Tissue: Placenta.
[3]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS THR-340 AND THR-521.
Tissue: Placenta.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Leukocyte and Lung.
[6]"The kinase domain of mitochondrial PINK1 faces the cytoplasm."
Zhou C., Huang Y., Shao Y., May J., Prou D., Perier C., Dauer W., Schon E.A., Przedborski S.
Proc. Natl. Acad. Sci. U.S.A. 105:12022-12027(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH PARK2, CHARACTERIZATION OF VARIANTS PARK6 PRO-126; ASP-309 AND PRO-347.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, INTERACTION WITH PARK2.
[10]"PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria."
Okatsu K., Oka T., Iguchi M., Imamura K., Kosako H., Tani N., Kimura M., Go E., Koyano F., Funayama M., Shiba-Fukushima K., Sato S., Shimizu H., Fukunaga Y., Taniguchi H., Komatsu M., Hattori N., Mihara K., Tanaka K., Matsuda N.
Nat. Commun. 3:1016-1016(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-228 AND SER-402.
[11]"The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy."
Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., Plun-Favreau H.
Nat. Neurosci. 16:1257-1265(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXO7.
[12]"PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria."
Chen Y., Dorn G.W. II
Science 340:471-475(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOPHAGY, MUTAGENESIS OF LYS-219; ASP-362 AND ASP-384.
[13]"PINK1 mutations are associated with sporadic early-onset parkinsonism."
Valente E.M., Salvi S., Ialongo T., Marongiu R., Elia A.E., Caputo V., Romito L., Albanese A., Dallapiccola B., Bentivoglio A.R.
Ann. Neurol. 56:336-341(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 PHE-92; PRO-168 AND HIS-464, VARIANTS LEU-296; THR-340; THR-442; LYS-476; THR-521 AND ASN-525.
[14]"Novel PINK1 mutations in early-onset parkinsonism."
Hatano Y., Li Y., Sato K., Asakawa S., Yamamura Y., Tomiyama H., Yoshino H., Asahina M., Kobayashi S., Hassin-Baer S., Lu C.-S., Ng A.R., Rosales R.L., Shimizu N., Toda T., Mizuno Y., Hattori N.
Ann. Neurol. 56:424-427(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 GLN-271; PRO-347 AND GLY-417.
[15]Erratum
Hatano Y., Li Y., Sato K., Asakawa S., Yamamura Y., Tomiyama H., Yoshino H., Asahina M., Kobayashi S., Hassin-Baer S., Lu C.-S., Ng A.R., Rosales R.L., Shimizu N., Toda T., Mizuno Y., Hattori N.
Ann. Neurol. 56:603-603(2004)
[16]"Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease."
Rogaeva E., Johnson J., Lang A.E., Gulick C., Gwinn-Hardy K., Kawarai T., Sato C., Morgan A., Werner J., Nussbaum R., Petit A., Okun M.S., McInerney A., Mandel R., Groen J.L., Fernandez H.H., Postuma R., Foote K.D. expand/collapse author list , Salehi-Rad S., Liang Y., Reimsnider S., Tandon A., Hardy J., St George-Hyslop P., Singleton A.B.
Arch. Neurol. 61:1898-1904(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 LYS-240; PRO-347 AND PRO-489, VARIANTS GLY-231; ILE-235; GLY-263; LEU-318; THR-339; THR-340; HIS-362; SER-425; LYS-476 AND THR-521.
[17]"PINK1 (PARK6) associated Parkinson disease in Ireland."
Healy D.G., Abou-Sleiman P.M., Gibson J.M., Ross O.A., Jain S., Gandhi S., Gosal D., Muqit M.M.K., Wood N.W., Lynch T.
Neurology 63:1486-1488(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 HIS-147.
[18]"Hereditary early-onset Parkinson's disease caused by mutations in PINK1."
Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M.K., Harvey K., Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., Albanese A., Nussbaum R., Gonzalez-Maldonado R., Deller T., Salvi S., Cortelli P., Gilks W.P., Latchman D.S. expand/collapse author list , Harvey R.J., Dallapiccola B., Auburger G., Wood N.W.
Science 304:1158-1160(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 ASP-309, CHARACTERIZATION OF VARIANT PARK6 ASP-309, FUNCTION, SUBCELLULAR LOCATION.
[19]"Analysis of PINK1 in Asian patients with familial parkinsonism."
Tan E.K., Yew K., Chua E., Shen H., Jamora R.D., Lee E., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Puvan K., Yih Y., Tan L.C.S.
Clin. Genet. 68:468-470(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 VAL-268.
[20]"PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism."
Klein C., Djarmati A., Hedrich K., Schaefer N., Scaglione C., Marchese R., Kock N., Schuele B., Hiller A., Lohnau T., Winkler S., Wiegers K., Hering R., Bauer P., Riess O., Abbruzzese G., Martinelli P., Pramstaller P.P.
Eur. J. Hum. Genet. 13:1086-1093(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 HIS-279 AND GLN-534 INS, VARIANT LEU-115.
[21]"Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism."
Silvestri L., Caputo V., Bellacchio E., Atorino L., Dallapiccola B., Valente E.M., Casari G.
Hum. Mol. Genet. 14:3477-3492(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PARK6 PRO-168 AND ASP-309.
[22]"Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism."
Li Y., Tomiyama H., Sato K., Hatano Y., Yoshino H., Atsumi M., Kitaguchi M., Sasaki S., Kawaguchi S., Miyajima H., Toda T., Mizuno Y., Hattori N.
Neurology 64:1955-1957(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 ARG-388.
[23]"Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes."
The Italian Parkinson genetics network
Bonifati V., Rohe C.F., Breedveld G.J., Fabrizio E., De Mari M., Tassorelli C., Tavella A., Marconi R., Nicholl D.J., Chien H.F., Fincati E., Abbruzzese G., Marini P., De Gaetano A., Horstink M.W., Maat-Kievit J.A., Sampaio C., Antonini A. expand/collapse author list , Stocchi F., Montagna P., Toni V., Guidi M., Dalla Libera A., Tinazzi M., De Pandis F., Fabbrini G., Goldwurm S., de Klein A., Barbosa E., Lopiano L., Martignoni E., Lamberti P., Vanacore N., Meco G., Oostra B.A.
Neurology 65:87-95(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 PRO-168 AND LEU-196, VARIANTS LEU-115; THR-340; LYS-476 AND THR-521.
[24]"A heterozygous effect for PINK1 mutations in Parkinson's disease?"
Abou-Sleiman P.M., Muqit M.M.K., McDonald N.Q., Yang Y.X., Gandhi S., Healy D.G., Harvey K., Harvey R.J., Deas E., Bhatia K., Quinn N., Lees A., Latchman D.S., Wood N.W.
Ann. Neurol. 60:414-419(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-317; THR-339; THR-383; SER-411; HIS-431; SER-451; SER-461; LYS-476; PRO-501 AND ARG-575, CHARACTERIZATION OF VARIANTS HIS-431; SER-451; LYS-476; PRO-501 AND ARG-575.
[25]"Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1."
Leutenegger A.-L., Salih M.A.M., Ibanez P., Mukhtar M.M., Lesage S., Arabi A., Lohmann E., Duerr A., Ahmed A.E.M., Brice A.
Arch. Neurol. 63:1257-1261(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 ASP-217.
[26]"T313M PINK1 mutation in an extended highly consanguineous Saudi family with early-onset Parkinson disease."
Chishti M.A., Bohlega S., Ahmed M., Loualich A., Carroll P., Sato C., St George-Hyslop P., Westaway D., Rogaeva E.
Arch. Neurol. 63:1483-1485(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 MET-313.
[27]"Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa."
The French Parkinson's disease genetics study group
Ibanez P., Lesage S., Lohmann E., Thobois S., De Michele G., Borg M., Agid Y., Durr A., Brice A.
Brain 129:686-694(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK6 GLY-125; LYS-240; PRO-369; ALA-386 AND VAL-409.
[28]"Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease."
Tang B., Xiong H., Sun P., Zhang Y., Wang D., Hu Z., Zhu Z., Ma H., Pan Q., Xia J.-H., Xia K., Zhang Z.
Hum. Mol. Genet. 15:1816-1825(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 LEU-399.
[29]"PINK1 mutations in sporadic early-onset Parkinson's disease."
Tan E.-K., Yew K., Chua E., Puvan K., Shen H., Lee E., Puong K.-Y., Zhao Y., Pavanni R., Wong M.-C., Jamora D., de Silva D., Moe K.-T., Woon F.-P., Yuen Y., Tan L.
Mov. Disord. 21:789-793(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 THR-280, VARIANTS THR-340 AND THR-521.
[30]"Analysis of the PINK1 gene in a cohort of patients with sporadic early-onset parkinsonism in Taiwan."
Fung H.-C., Chen C.-M., Hardy J., Singleton A.B., Lee-Chen G.-J., Wu Y.-R.
Neurosci. Lett. 394:33-36(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 GLN-407, VARIANTS THR-340 AND THR-521.
[31]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] TRP-148; SER-196; LEU-209; LEU-215; THR-339; THR-340; ILE-341; PHE-377; THR-477 AND THR-521.
[32]"PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum."
The Italian PD study group
Marongiu R., Ferraris A., Ialongo T., Michiorri S., Soleti F., Ferrari F., Elia A.E., Ghezzi D., Albanese A., Altavista M.C., Antonini A., Barone P., Brusa L., Cortelli P., Martinelli P., Pellecchia M.T., Pezzoli G., Scaglione C. expand/collapse author list , Stanzione P., Tinazzi M., Zecchinelli A., Zeviani M., Cassetta E., Garavaglia B., Dallapiccola B., Bentivoglio A.R., Valente E.M.
Hum. Mutat. 29:565-565(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHE-67; PRO-68; TRP-98; SER-111; VAL-124; MET-145; ASN-186; ILE-257 VAL-268; GLN-276; LEU-296; ILE-317; LEU-322; THR-339; THR-383; VAL-395; THR-442; LYS-476; ASN-525 AND THR-537.
[33]"Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation."
Prestel J., Gempel K., Hauser T.K., Schweitzer K., Prokisch H., Ahting U., Freudenstein D., Bueltmann E., Naegele T., Berg D., Klopstock T., Gasser T.
J. Neurol. 255:643-648(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 PRO-126.
[34]"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. expand/collapse author list , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK6 PRO-347.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB053323 mRNA. Translation: BAB55647.1.
AF316873 mRNA. Translation: AAK28062.1.
AK075225 mRNA. Translation: BAC11484.1.
AL391357 Genomic DNA. Translation: CAH73475.1.
BC009534 mRNA. Translation: AAH09534.1.
BC028215 mRNA. Translation: AAH28215.1.
RefSeqNP_115785.1. NM_032409.2.
UniGeneHs.389171.

3D structure databases

ProteinModelPortalQ9BXM7.
SMRQ9BXM7. Positions 246-545.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122376. 48 interactions.
DIPDIP-29427N.
IntActQ9BXM7. 8 interactions.
MINTMINT-6781189.
STRING9606.ENSP00000364204.

PTM databases

PhosphoSiteQ9BXM7.

Polymorphism databases

DMDM48428484.

Proteomic databases

PaxDbQ9BXM7.
PRIDEQ9BXM7.

Protocols and materials databases

DNASU65018.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321556; ENSP00000364204; ENSG00000158828. [Q9BXM7-1]
GeneID65018.
KEGGhsa:65018.
UCSCuc001bdm.3. human. [Q9BXM7-1]
uc001bdn.3. human. [Q9BXM7-2]

Organism-specific databases

CTD65018.
GeneCardsGC01P020959.
HGNCHGNC:14581. PINK1.
HPACAB026191.
HPA001931.
MIM168600. phenotype.
605909. phenotype.
608309. gene.
neXtProtNX_Q9BXM7.
Orphanet2828. Young adult-onset Parkinsonism.
PharmGKBPA33325.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231649.
HOVERGENHBG053601.
InParanoidQ9BXM7.
KOK05688.
OMAGPKQLAP.
OrthoDBEOG7TBC1R.
PhylomeDBQ9BXM7.
TreeFamTF313183.

Enzyme and pathway databases

SignaLinkQ9BXM7.

Gene expression databases

BgeeQ9BXM7.
CleanExHS_PINK1.
GenevestigatorQ9BXM7.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPINK1. human.
GeneWikiPINK1.
GenomeRNAi65018.
NextBio67218.
PROQ9BXM7.
SOURCESearch...

Entry information

Entry namePINK1_HUMAN
AccessionPrimary (citable) accession number: Q9BXM7
Secondary accession number(s): Q8N6T9, Q8NBU3, Q96DE4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM