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FLASH GENE
Symbol ADAM22 contributors: npt/mct - updated : 10-05-2017
HGNC name ADAM metallopeptidase domain 22
HGNC id 201
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • domains similar to hemorrhagic snake venom proteins (HSVP)
  • a disrupted Zn-binding site metalloproteinase
  • a disintegrin-like domains
  • a cysteine-rich domain
  • an EGF-like repeat
  • a transmembrane domain and a cytoplasmic tail
  • a peptidase M12B domain
  • extracellular domain interacting with LGI1, whereas its cytoplasmic PDZ-binding motif recruits DLG4 (Liu 2009)
  • ectodomain comprising four domains assembled together like a four-leaf clover, and each leaf represents one of the four domains including :
  • the metalloproteinase-like domain (domain M, residues 233–435)
  • the disintegrin domain (domain D, residues 445–529)
  • the cysteine-rich domain (domain C, residues 530–676)
  • the epidermal growth factor-like domain (domain E, residues 677–718) (Liu 2009)
    • conjugated GlycoP , MetalloP
    isoforms Precursor the propeptide of ADAM22 is essential for ADAM22 secretion and may play an intramolecular chaperone function, similar to the cases of ADAM17 and ADAM12
    HOMOLOGY
    Homologene
    FAMILY
  • ADAM (a disintegrin and metalloprotease domain) family
    • CATEGORY adhesion , enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    text anchored to the postsynaptic density by cytoskeletal scaffolds containing stargazin
    basic FUNCTION
  • involved in cell-cell and cell-matrix interactions integrin ligand in the brain
  • brain-specific cell surface protein, mediates growth inhibition using an integrin dependent pathway
  • non-catalytic ADAMs, recently identified to serve as the postsynaptic receptor for the secreted neurotransmission modulator LGI1 at neural synapses (Liu 2009)
  • by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains likely physiological brain excitability throughout life
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS development
    text neurogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • form a tertiary complex with postsynaptic density-95 (DLG4), a major scaffolding protein localized to the postsynaptic density of brain synapse (Liu 2009)
  • LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of DLG4
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • three putative calcium ions bound to ADAM22
    • protein
  • probable ligand for integrin in the brain
  • coupling to LGI1, enhancing AMPA receptor-mediated synaptic transmission in hippocampal slices
  • interacting with LGI1 (LGI1acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission)
  • interaction with YWHAZ (can regulate cell adhesion and spreading, therefore it has a potential role in neural development and function)
  • with ADAM11 and ADAM23, binds LGI1 and LGI4 (LGI-ADAM system seems to be regulated not only by the affinity but also by the cell-type-specific expression of each protein) (Sagane 2008)
  • critical roles of a ligand-receptor complex, LGI1-ADAM22, in synaptic transmission and brain function
  • is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons
  • ADAM22 and ADAM23 modulate the trafficking of LGI1, and promote its ER export and expression at the overall neuronal cell surface
  • ADAM22 may be an LGI3 receptor in human keratinocytes (PMID/
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEECA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    high-grade but not low-grade gliomas
    tumoral     --low  
    low expression levels of LGI3, ADAM22 and ADAM23 were significantly associated with poor prognosis of glioma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS