InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PINK1

Summary

InnateDB Protein

IDBP-92924.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PINK1

Protein Name

PTEN induced putative kinase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000364204

InnateDB Gene

IDBG-92922 (PINK1)

Protein Structure

UniProt Annotation

Function

Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PARK2. Targets PARK2 to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Activates PARK2 in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PARK2 and (2) mediating phosphorylation of ubiquitin, converting PARK2 to its fully-active form. {ECO:0000269PubMed:14607334, ECO:0000269PubMed:15087508, ECO:0000269PubMed:19966284, ECO:0000269PubMed:20404107, ECO:0000269PubMed:20798600, ECO:0000269PubMed:23620051, ECO:0000269PubMed:23754282, ECO:0000269PubMed:23933751, ECO:0000269PubMed:24784582, ECO:0000269PubMed:24896179}.

Subcellular Localization

Mitochondrion outer membrane; Single-pass membrane protein. Cytoplasm, cytosol.

Disease Associations

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. {ECO:0000269PubMed:15087508, ECO:0000269PubMed:15349860, ECO:0000269PubMed:15349870, ECO:0000269PubMed:15505171, ECO:0000269PubMed:15596610, ECO:0000269PubMed:15955953, ECO:0000269PubMed:15970950, ECO:0000269PubMed:16009891, ECO:0000269PubMed:16207217, ECO:0000269PubMed:16257123, ECO:0000269PubMed:16401616, ECO:0000269PubMed:16482571, ECO:0000269PubMed:16632486, ECO:0000269PubMed:16966503, ECO:0000269PubMed:17030667, ECO:0000269PubMed:18286320, ECO:0000269PubMed:22956510}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:11494141}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 83 experimentally validated interaction(s) in this database.

Experimentally validated
Total	83 [view]
Protein-Protein	79 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0010857	calcium-dependent protein kinase activity
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031625	ubiquitin protein ligase binding
GO:0055131	C3HC4-type RING finger domain binding

Biological Process

GO:0000422	mitochondrion degradation
GO:0006468	protein phosphorylation
GO:0006950	response to stress
GO:0008219	cell death
GO:0016567	protein ubiquitination
GO:0018105	peptidyl-serine phosphorylation
GO:0031396	regulation of protein ubiquitination
GO:0032226	positive regulation of synaptic transmission, dopaminergic
GO:0033603	positive regulation of dopamine secretion
GO:0033605	positive regulation of catecholamine secretion
GO:0035556	intracellular signal transduction
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043254	regulation of protein complex assembly
GO:0043523	regulation of neuron apoptotic process
GO:0043524	negative regulation of neuron apoptotic process
GO:0090200	positive regulation of release of cytochrome c from mitochondria
GO:0097237	cellular response to toxic substance
GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway

Cellular Component

GO:0000785	chromatin
GO:0005634	nucleus
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005743	mitochondrial inner membrane
GO:0005758	mitochondrial intermembrane space
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0016020	membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt