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FLASH GENE
Symbol GAK contributors: mct - updated : 14-11-2017
HGNC name cyclin G associated kinase
HGNC id 4113
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticspleen    
Cardiovascularheart    
Digestivesalivary gland   highly
Endocrineparathyroid   highly
Nervousnervecranial nerve  highly
Reproductivemale systemtestis  moderately
Respiratorylung    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Lymphoid    
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, G1
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal serine/threonine kinase domain
  • a tensin/auxillin homologous domain
  • a DNAJ domain
  • a consensus phosphorylation motif (Y412) for SRC
  • a C-terminal J-domain, essential for clathrin recycling from endocytic vesicles
  • HOMOLOGY
    intraspecies homolog to DNAJC6
    Homologene
    FAMILY ser/thr family of protein kinases
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    intracellular,nuclear envelope,ext
    text
  • perinuclear area and to the trans-Golgi network
  • on the plasma membrane, probably at focals adhesions
  • GAK localizes in both cytoplasm and nucleus
  • translocated from the centrosome to chromatin at the end of telophase
  • basic FUNCTION
  • may be acting as an auxilin homolog that is involved in the uncoating of clathrin- coated vesicles by hsc70 in non-neuronal cell
  • regulates clathrin-mediated membrane trafficking in the cytoplasm
  • important function of GAK in the nucleus
  • two novel functions of GAK: maintenance of proper centrosome maturation and of mitotic chromosome congression
  • GAK and CLTC function cooperatively not only in endocytosis, but also in mitotic progression
  • is a novel regulator of microtubule generation at kinetochores/chromatin
  • role for GAK and clathrin in microtubule outgrowth from kinetochores/chromosomes, suggesting that GAK acts through clathrin to control microtubule outgrowth around chromosomes
  • acting as a protein serine/threonine kinase
  • is a key regulator of clathrin-coated vesicle trafficking and plays a central role during development
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    text
  • regulation of cell cycle
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    ATP
    protein
  • binding to cyclin G and CDK5
  • is an essential cofactor for HSPA8-dependent uncoating of clathrin-coated vesicles
  • interaction of GAK with adaptor protein 1 (JUN) regulates lysosomal enzyme sorting
  • GAK and SNCA interact in a pathway involved in Parkinson disease pathogenesis
  • interacting with CREBBP, in embryonic orofacial tissue
  • GAK modifies SNCA expression levels and affects susceptibility to Parkinson disease
  • cell & other
    REGULATION
    induced by TP53 (direct transcriptional target of the p53 tumor suppressor gene)
    Phosphorylated by phosphorylated by SRC not only at Y412 but also at Y1149
    Other expression oscillates slightly during the cell cycle,peaking at G1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in both osteosarcoma cell lines and tissue samples when compared with human osteoblasts
    Susceptibility to Parkinson disease (PD)
    Variant & Polymorphism other
  • GAK rs1564282 C/T polymorphism is associated with increased susceptibility to PD
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    is an attractive therapeutic target for the treatment of PD
    ANIMAL & CELL MODELS