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FLASH GENE
Symbol GAK contributors: mct - updated : 14-11-2017
HGNC name cyclin G associated kinase
HGNC id 4113
Location 4p16.3      Physical location : 843.065 - 926.174
Synonym name
  • DnaJ (Hsp40) homolog, subfamily B, member 6
  • DnaJ (Hsp40) homolog, subfamily C, member 6
  • auxilin 2
  • Synonym symbol(s) FLJ40395, MGC99654, DNAJ26, DNAJC26
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 83.12 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    PCDH18 4q31.2-q32 protocadherin 18 LOC389255 4 similar to RSTI689 LOC152687 4p16.3 hypothetical protein LOC152687 AMBN 4q21 ameloblastin, enamel matrix protein FLJ90036 4p16.3 hypothetical protein FLJ90036 LOC391611 4 similar to Zinc finger protein 208 ZNF141 4p16.3 zinc finger protein 141 (clone pHZ-44) FLJ14297 4p16.3 hypothetical protein FLJ14297 FLJ20265 4p16.3 hypothetical protein FLJ20265 PDE6B 4p16.3 phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant) ATP5I 4p16.3 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit e MYL5 4p16.3 myosin, light polypeptide 5, regulatory FLJ22269 4p16.3 hypothetical protein FLJ22269 RNF3 4p16.3 ring finger protein 3 CPLX1 4p16.3 complexin 1 GAK 4p16 cyclin G associated kinase MGC4618 4p16.3 hypothetical protein MGC4618 DGKQ 4p16.3 diacylglycerol kinase, theta 110kDa SLC26A1 4p16.3 solute carrier family 26 (sulfate transporter), member 1 IDUA 4p16.3 iduronidase, alpha-L- FGFRL1 4p16 fibroblast growth factor receptor-like 1 LOC285498 4p16.3 hypothetical protein LOC285498 LOC132969 4p16.3 similar to hornerin SPON2 4p16.3 spondin 2, extracellular matrix protein CTBP1 4p16 C-terminal binding protein 1 MGC21675 4p16.3 hypothetical protein MGC21675 MAEA 4p16.3 macrophage erythroblast attacher KIAA1530 4p16.3 KIAA1530 protein FLJ34443 4p16.3 hypothetical protein FLJ34443 HSPX153 4p16.3 HPX-153 homeobox LOC345375 4p16.3 similar to CG32656-PA LOC152877 4p16.3 similar to RIKEN cDNA 5430419M09 SLBP 4p16 stem-loop (histone) binding protein LOC92305 4p16.3 hypothetical protein BC009331 TACC3 4p16.3 transforming, acidic coiled-coil containing protein 3 FGFR3 4p16.3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) LETM1 4p16.3 leucine zipper-EF-hand containing transmembrane protein 1 WHSC1 4p16.3 Wolf-Hirschhorn syndrome candidate 1 WHSC2 4p16.3 Wolf-Hirschhorn syndrome candidate 2 LOC389195 4 hypothetical gene supported by BC038466; BC047038 FLJ37478 4p16.3 hypothetical protein FLJ37478 POLN 4p16.3 polymerase (DNA directed) nu MGC4701 4p16.3 hypothetical protein MGC4701 MXD4 4p16.3 MAX dimerization protein 4 KIAA1643 4p16.3 KIAA1643 protein LOC339985 4p16.3 hypothetical gene supported by BC010180 RNF4 4p16.3 ring finger protein 4 C4orf8 4p16.3 chromosome 4 open reading frame 8 TNIP2 4p16.3 TNFAIP3 interacting protein 2 LOC389196 4 LOC389196 SH3BP2 4p16.3 SH3-domain binding protein 2 ADD1 4p16.3 adducin 1 (alpha) TETRAN 4p16.3 tetracycline transporter-like protein C4orf9 4p16.3 chromosome 4 open reading frame 9 GPRK2L 4p16.3 G protein-coupled receptor kinase 2-like (Drosophila) HD 4p16.3 huntingtin (Huntington disease) LOC345222 4p16.3 hypothetical gene supported by BC043530 RGS12 4p16.3 regulator of G-protein signalling 12 HGFAC 4p16.3 HGF activator FLJ33718 4p16.3 hypothetical protein FLJ33718
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 4315 - 1232 - 2017 28135906
    28 - 4552 - 1311 - 2017 28135906
    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