UniProt functional annotation for Q5S007

UniProt code: Q5S007.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Positively regulates autophagy through a calcium- dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852}.
 
Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
Subunit: Homodimer. Interacts with PARK2, PRDX3, RAB29, TPCN2 and VPS35. {ECO:0000269|PubMed:16352719, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:22952686, ECO:0000269|PubMed:23395371}.
Subcellular location: Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:24687852}; Peripheral membrane protein {ECO:0000269|PubMed:24687852}; Cytoplasmic side {ECO:0000269|PubMed:24687852}. Endosome {ECO:0000250}. Lysosome {ECO:0000250}. Mitochondrion outer membrane {ECO:0000250}. Mitochondrion inner membrane {ECO:0000250}. Mitochondrion matrix {ECO:0000250}. Note=Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity). Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes. {ECO:0000250}.
Tissue specificity: Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas. {ECO:0000269|PubMed:15541308, ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:16532471, ECO:0000269|PubMed:17120249}.
Domain: The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins. {ECO:0000269|PubMed:24687852}.
Domain: The Roc domain mediates homodimerization and regulates kinase activity. {ECO:0000269|PubMed:18230735}.
Ptm: Autophosphorylated.
Disease: Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. {ECO:0000269|PubMed:15541308, ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:15680455, ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457, ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108, ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371, ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:15925109, ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16102999, ECO:0000269|PubMed:16157901, ECO:0000269|PubMed:16157908, ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16240353, ECO:0000269|PubMed:16247070, ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164, ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482, ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:16333314, ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18213618, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:23395371}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.