Q9BXM7 (PINK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	581 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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). It is necessary for PARK2 recruitment to dysfunctional mitochondria to initiate their degradation. Ref.2 Ref.7 Ref.8 Ref.9 Ref.16
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.2
Subunit structure	Interacts with PARK2. Ref.7 Ref.9
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein. Cytoplasm › cytosol Ref.6 Ref.7 Ref.16.
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.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.31
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Autophagy
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Neurodegeneration Parkinsonism
Domain	Transit peptide Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular response to toxin Inferred from electronic annotation. Source: Compara intracellular protein kinase cascade Inferred from direct assay Ref.2. Source: UniProtKB mitochondrion degradation Inferred from mutant phenotype Ref.7. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from direct assay PubMed 19880420. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay PubMed 19880420. Source: BHF-UCL positive regulation of dopamine secretion Inferred from electronic annotation. Source: Compara 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: Compara 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.16. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.7. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay Ref.16Ref.7. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.2. Source: UniProtKB calcium-dependent protein kinase activity Inferred from direct assay PubMed 19880420. Source: BHF-UCL magnesium ion binding Inferred from direct assay Ref.2. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHOT1	Q8IXI2	3	EBI-2846068,EBI-1396430

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 77	77	Mitochondrion Potential
	Chain	78 – 581	504	Serine/threonine-protein kinase PINK1, mitochondrial		PRO_0000024369
Regions
	Topological domain	78 – 93	16	Mitochondrial intermembrane Potential
	Transmembrane	94 – 110	17	Helical; Potential
	Topological domain	111 – 581	471	Cytoplasmic Potential
	Domain	156 – 511	356	Protein kinase
	Nucleotide binding	162 – 170	9	ATP By similarity UniProtKB Q02750
Sites
	Active site	362	1	Proton acceptor By similarity UniProtKB Q02750
	Binding site	186	1	ATP By similarity
Amino acid modifications
	Modified residue	228	1	Phosphoserine; by autocatalysis Ref.10
	Modified residue	402	1	Phosphoserine; by autocatalysis Ref.10
Natural variations
	Alternative sequence	1 – 307	307	Missing in isoform 2.		VSP_050754
	Alternative sequence	308 – 320	13	LGHGR…LVMKN → MCGSQRPSPLSTS in isoform 2.		VSP_050755
	Natural variant	67	1	L → F. Ref.30		VAR_046566
	Natural variant	68	1	R → P. Ref.30		VAR_046567
	Natural variant	92	1	C → F in PARK6. Ref.11		VAR_046568
	Natural variant	98	1	R → W. Ref.30		VAR_046569
	Natural variant	111	1	I → S. Ref.30		VAR_046570
	Natural variant	115	1	Q → L. Ref.18 Ref.21		VAR_046571
	Natural variant	124	1	A → V. Ref.30		VAR_046572
	Natural variant	125	1	C → G in PARK6. Ref.25		VAR_062773
	Natural variant	126	1	Q → P in PARK6; strongly reduces interaction with PARK2. Ref.7 Ref.31		VAR_064344
	Natural variant	145	1	T → M. Ref.30 Corresponds to variant rs45604240 [ dbSNP | Ensembl ].		VAR_046573
	Natural variant	147	1	R → H in PARK6; uncertain pathogenicity. Ref.15		VAR_046574
	Natural variant	148	1	L → W. Ref.29 Corresponds to variant rs56297806 [ dbSNP | Ensembl ].		VAR_041010
	Natural variant	168	1	A → 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.11 Ref.19 Ref.21		VAR_046575
	Natural variant	186	1	K → N. Ref.30		VAR_046576
	Natural variant	196	1	P → L in PARK6. Ref.21		VAR_046577
	Natural variant	196	1	P → S. Ref.29 Corresponds to variant rs35802484 [ dbSNP | Ensembl ].		VAR_041011
	Natural variant	209	1	P → L. Ref.29 Corresponds to variant rs34677717 [ dbSNP | Ensembl ].		VAR_041012
	Natural variant	215	1	P → L in a glioblastoma multiforme sample; somatic mutation. Ref.29		VAR_041013
	Natural variant	217	1	A → D in PARK6. Ref.23		VAR_046578
	Natural variant	231	1	E → G. Ref.14		VAR_046579
	Natural variant	235	1	N → I. Ref.14		VAR_046580
	Natural variant	240	1	E → K in PARK6. Ref.14 Ref.25		VAR_046581
	Natural variant	257	1	T → I. Ref.30		VAR_046582
	Natural variant	263	1	R → G. Ref.14		VAR_046583
	Natural variant	268	1	L → V in PARK6. Ref.17 Ref.30		VAR_046584
	Natural variant	271	1	H → Q in PARK6. Ref.12		VAR_046585
	Natural variant	276	1	R → Q. Ref.30		VAR_046586
	Natural variant	279	1	R → H in PARK6. Ref.18		VAR_046587
	Natural variant	280	1	A → T in PARK6; early-onset. Ref.27		VAR_062774
	Natural variant	296	1	P → L. Ref.11 Ref.30		VAR_046588
	Natural variant	305	1	P → L. Corresponds to variant rs7349186 [ dbSNP | Ensembl ].		VAR_018993
	Natural variant	309	1	G → 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.16 Ref.19		VAR_018994
	Natural variant	313	1	T → M in PARK6. Ref.24		VAR_046589
	Natural variant	317	1	V → I. Ref.22 Ref.30		VAR_046590
	Natural variant	318	1	M → L. Ref.14		VAR_046591
	Natural variant	322	1	P → L. Ref.30		VAR_046592
	Natural variant	339	1	A → T. Ref.14 Ref.22 Ref.29 Ref.30 Corresponds to variant rs55831733 [ dbSNP | Ensembl ].		VAR_041014
	Natural variant	340	1	A → T. Ref.3 Ref.11 Ref.14 Ref.21 Ref.27 Ref.28 Ref.29 Corresponds to variant rs3738136 [ dbSNP | Ensembl ].		VAR_018995
	Natural variant	341	1	M → I. Ref.29 Corresponds to variant rs35813094 [ dbSNP | Ensembl ].		VAR_041015
	Natural variant	347	1	L → P in PARK6; strongly reduces interaction with PARK2. Ref.7 Ref.12 Ref.14		VAR_046593
	Natural variant	362	1	D → H. Ref.14		VAR_046594
	Natural variant	369	1	L → P in PARK6. Ref.25		VAR_062775
	Natural variant	377	1	C → F. Ref.29 Corresponds to variant rs34203620 [ dbSNP | Ensembl ].		VAR_041016
	Natural variant	383	1	A → T. Ref.22 Ref.30 Corresponds to variant rs45515602 [ dbSNP | Ensembl ].		VAR_046595
	Natural variant	386	1	G → A in PARK6. Ref.25		VAR_062776
	Natural variant	388	1	C → R in PARK6. Ref.20		VAR_046596
	Natural variant	395	1	G → V. Ref.30		VAR_046597
	Natural variant	399	1	P → L in PARK6; digenic inheritance; associated with Ser-39 mutation in PARK7 gene. Ref.26		VAR_062777
	Natural variant	407	1	R → Q in PARK6; early-onset. Ref.28		VAR_062778
	Natural variant	409	1	G → V in PARK6. Ref.25		VAR_062779
	Natural variant	411	1	G → S. Ref.22 Corresponds to variant rs45478900 [ dbSNP | Ensembl ].		VAR_046598
	Natural variant	417	1	E → G in PARK6. Ref.12		VAR_046599
	Natural variant	425	1	P → S. Ref.14		VAR_046600
	Natural variant	431	1	Y → H May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.22		VAR_046601
	Natural variant	442	1	I → T. Ref.11 Ref.30		VAR_046602
	Natural variant	451	1	N → S May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.22		VAR_046603
	Natural variant	461	1	L → S. Ref.22		VAR_046604
	Natural variant	464	1	R → H in PARK6. Ref.11		VAR_046605
	Natural variant	476	1	E → K May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.11 Ref.14 Ref.21 Ref.22 Ref.30		VAR_046606
	Natural variant	477	1	S → T. Ref.29 Corresponds to variant rs34416410 [ dbSNP | Ensembl ].		VAR_041017
	Natural variant	489	1	L → P in PARK6. Ref.14		VAR_046607
	Natural variant	501	1	R → P May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.22		VAR_046608
	Natural variant	521	1	N → T. Ref.3 Ref.11 Ref.14 Ref.21 Ref.27 Ref.28 Ref.29 Corresponds to variant rs1043424 [ dbSNP | Ensembl ].		VAR_018996
	Natural variant	525	1	D → N. Ref.11 Ref.30		VAR_046609
	Natural variant	534	1	Q → QQ in PARK6. Ref.18		VAR_046610
	Natural variant	537	1	A → T. Ref.30		VAR_046611
	Natural variant	575	1	C → R May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. Ref.22		VAR_046612
Experimental info
	Sequence conflict	209	1	P → A in AAH28215. Ref.5
	Sequence conflict	419	1	S → P in BAC11484. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 721FE01F63263A64	FASTA	581	62,769
	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
	Isoform 2 [UniParc]. Checksum: C54C628F879B4BED	FASTA	274	30,104
	10 20 30 40 50 60 MCGSQRPSPL STSYPCTLRQ YLCVNTPSPR LAAMMLLQLL EGVDHLVQQG IAHRDLKSDN 70 80 90 100 110 120 ILVELDPDGC PWLVIADFGC CLADESIGLQ LPFSSWYVDR GGNGCLMAPE VSTARPGPRA 130 140 150 160 170 180 VIDYSKADAW AVGAIAYEIF GLVNPFYGQG KAHLESRSYQ EAQLPALPES VPPDVRQLVR 190 200 210 220 230 240 ALLQREASKR PSARVAANVL HLSLWGEHIL ALKNLKLDKM VGWLLQQSAA TLLANRLTEK 250 260 270 CCVETKMKML FLANLECETL CQAALLLCSW RAAL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
[12]	"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.
[13]	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)
[14]	"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. , 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.
[15]	"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.
[16]	"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. , 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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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. , 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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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. , 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.
[30]	"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. , 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.
[31]	"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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.
IPI	IPI00307065. IPI00411562.
RefSeq	NP_115785.1. NM_032409.2.
UniGene	Hs.389171.
3D structure databases
ProteinModelPortal	Q9BXM7.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29427N.
IntAct	Q9BXM7. 4 interactions.
STRING	9606.ENSP00000364204.
PTM databases
PhosphoSite	Q9BXM7.
Polymorphism databases
DMDM	48428484.
Proteomic databases
PaxDb	Q9BXM7.
PRIDE	Q9BXM7.
Protocols and materials databases
DNASU	65018.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000321556; ENSP00000364204; ENSG00000158828.
GeneID	65018.
KEGG	hsa:65018.
UCSC	uc001bdm.3. human. uc001bdn.3. human.
Organism-specific databases
CTD	65018.
GeneCards	GC01P020959.
HGNC	HGNC:14581. PINK1.
HPA	CAB026191. HPA001931.
MIM	168600. phenotype. 605909. phenotype. 608309. gene.
neXtProt	NX_Q9BXM7.
Orphanet	2828. Young adult-onset Parkinsonism.
PharmGKB	PA33325.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231649.
HOVERGEN	HBG053601.
InParanoid	Q9BXM7.
KO	K05688.
OMA	HGRTLFL.
OrthoDB	EOG480HW9.
PhylomeDB	Q9BXM7.
Gene expression databases
Bgee	Q9BXM7.
CleanEx	HS_PINK1.
Genevestigator	Q9BXM7.
GermOnline	ENSG00000158828. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PINK1. human.
GenomeRNAi	65018.
NextBio	67218.
SOURCE	Search...

Entry information

Entry name

PINK1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 116 of the entry and version 1 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.