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FLASH GENE
Symbol ZDHHC17 contributors: mct/npt - updated : 23-02-2016
HGNC name zinc finger, DHHC-type containing 17
HGNC id 18412
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • HIP14 PEP1 domain
  • five ankyrin repeat domains
  • four transmembrane domains
  • DHHC-type zinc finger
  • HOMOLOGY
    interspecies homolog to yeast S. Cerevisiae Akr1p
    intraspecies paralog to ZDHHC13
    Homologene
    FAMILY
  • DHHC palmitoyltransferase family
  • AKR/ZDHHC17 subfamily
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • localization within the presynaptic nerve terminal (Stowers 2007)
  • with ZDHHC17, co-localized to the Golgi and the same post-Golgi vesicles, suggesting that heteropalmitoylation might play a physiological role in addition to a biochemical function (Hines 2010)
  • basic FUNCTION
  • playing a role in intracellular trafficking and endocytosis
  • acting as a protein palmitoyltransferase and having an oncogenic potential
  • palmitoyl transferase involved in the palmitoylation and trafficking of multiple neuronal proteins
  • having palmitoyl acyltransferase activity through innate cysteine-rich domains, DHHC (Goytain 2008)
  • encode Mg2+ transport proteins that are regulated by their innate palmitoyl acyltransferases thus fulfilling the characteristics of "chanzymes", proteins combining transport and enzymatic functions (Goytain 2008)
  • controls neurotransmitter release by regulating the trafficking of cysteine string protein to synapses (Ohyama 2007)
  • is the only ZDHHC gene transcribed in normal human erythroid cells
  • DHHC17, DHHC18, DHHC20, and DHHC21 exhibited weak or moderate activities
  • is critically involved in behavioral modulation of striatal processing
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binds to HTT and robustly palmitoylates HTT at cysteine 214
  • ZDHHC17 is the major CLIP3 palmitoyltransferase, that modulates CLI3 plasma membrane binding, thereby regulating AKT1 signaling and SLC2A4 membrane translocation in adipocytes
  • it is possible that optineurin regulates trafficking of ZDHHC17 to its substrates
  • GPM6A, and the Sprouty domain-containing proteins SPRED1 and SPRED3, are indeed palmitoylated by ZDHHC17
  • HTT is palmitoylated by ZDHHC17 and 13
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    in the absence of ZDHHC17, striatal neurons become dysfunctional, leading to impaired motor behavior
    constitutional     --low  
    lack or marked decrease of the DHHC17 protein might lead to changes in membrane lateral organization
    constitutional     --low  
    loss of palmitoylation of MPP1 attributable to absence of DHHC17 membrane associated with hemolytic anemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice deficient for Zdhhc17 expression develop neuropathological and behavioural features similar to HD, and the catalytic activity of Zdhhc13 is impaired in HD mice, most likely due to the reduced interaction of Zdhhc17 with Htt
  • loss of Zdhhc17 and Zdhhc13 leads to early embryonic lethality at day embryonic day 10-11 due to failed chorioallantoic fusion