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FLASH GENE

Symbol

ADAM22

contributors: npt/mct - updated : 10-05-2017

HGNC name	ADAM metallopeptidase domain 22
HGNC id	201

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Nervous brain limbic system hippocampus   highly   brain hindbrain cerebellum   highly   nerve cranial nerve         spinal cord       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous glia Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

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

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

EIEECA

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   high-grade but not low-grade gliomas

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS