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FLASH GENE

Symbol

AFDN

contributors: mct - updated : 06-02-2018

HGNC name	afadin
HGNC id	7137

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 blood / hematopoietic spleen         Digestive liver         Hearing/Equilibrium ear inner cochlea   highly Nervous brain limbic system hippocampus     Homo sapiens Reproductive male system testis     highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

pancreas

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two N terminal Ras-binding-domains (RBD)
	U104 and DIL motifs described respectively in microtubules and actin-based motor proteins
	a PDZ domain (AFPDZ) responsible for binding the cytoplasmic C-terminus of nectins
	an F-actin binding domain to connect the cytoskeleton with transmembrane proteins at cellular junctions
	Ras binding sites that interact with and regulate the small GTPases RAS and RAP1 (Ras association (RA) domains, effector of RRas inducing axon branching through F-actin reorganization)
	an extended C terminal tail interferred with proline-rich patches

HOMOLOGY

interspecies	homolog to trithorax Drosophila
	homolog to afadin,large (p205) and small (p190) varieties of AF-6 protein

Homologene

FAMILY

CATEGORY

adhesion , signaling

SUBCELLULAR LOCALIZATION	plasma membrane,junction,adherens
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	synaptic localization for PVRL1 and MLLT4 are F-actin-dependent and the shedding of PVRL1 is a mechanism contributing to synaptic plasticity
	located at cell-cell adherens junctions
	key component of epithelial junctions
	localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle

basic FUNCTION	may be acting as an intracellular signaling component controlled by ras signaling pathways
	plays a role in formation and maintenance of cell junctions
	involved not only in the assembly of nectins and cadherins at synapses, but also in synaptic remodeling
	has a key role during development, through its regulatory role in cell-cell junction organization
	plays crucial roles, independently of the role as the nectin-afadin module, in barrier function and homeostasis of the intestinal epithelia
	LRPAP1-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other cell adhesion molecules and receptors
	key intracellular signaling molecule for cadherin recruitment and is necessary for spine and synapse formation
	may be a target for cAMP/RAPGEF3/RAP1A signalling at electrical synapses
	is required for the maintenance of dendritic structure and excitatory tone
	is required for the maintenance of dendritic architecture and excitatory inputs
	is likely required for the proper maintenance of dendritic fields through the coordinated regulation of both synapse number and function
	is essential for the maintenance of Adherens junctions (AJs) in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain
	regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons
	is an important regulator of cell-cell adhesion
	filamentous actin-binding protein and a mediator of nectin signaling
	remarkable function of afadin, which was able to enhance cytokine expression through TERF2IP activation in keratinocytes during inflammation
	is a potential inhibitor of metastasis in pancreatic cancer cells
	afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse
	F-actin-binding protein afadin is required for lumen continuity in developing renal tubules
	is required for lumen continuity by orienting the mitotic spindle during cell division

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

dimerization facilitates formation of a complex with MLLT4 and PDZGEF2 that activates RAP1A, which regulates beta1 integrin levels and cell migration

INTERACTION

DNA

RNA

small molecule

protein	binding partner of RAP1A, associating with profilin (PFN*), TJP1, occludin (OCLN)
	interacting with SRC (SRC colocalizes with MLLT4 at cell
	cell junctions in epithelial cells, and stimulation of cells with EGF increases MLLT4-dependent recruitment of SRC to these sites)
	binding of MLLT4 to RAP1A regulated the activity of RAP1A in a positive-feedback manner
	binding of JAG1 intracellular region to the PDZ domain of afadin couples Notch signaling with the adhesion system and the cytoskeleton
	interacts with the cytoplasmic region of nectins, which are immunoglobulin-like cell adhesion molecules at adherens junctions, and links them to the actin cytoskeleton
	association of GJD2 with MLLT4 and MPDZ, which required the C-terminus PDZ domain interaction motif of GJD2 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MPDZ
	interaction with RRAS in cortical neurons during the stage of axonal development
	afadin directly interacts with GRIA2, potentially via its type II PDZ domain, mechanistically linking the coordination of surface expression of AMPARs to synapse and dendrite structure
	PLEKHA7 bound to AFDN in addition to CTNND1 and was associated with nectin by binding to AFDN
	links nectins to the actin cytoskeleton
	critical role of the AFDN-ARHGAP29 axis for the regulation of RHO-associated kinase activity during vascular endothelial growth factor-induced network formation and migration of HUVECs

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       fused with HRX (MLL), in acute myeloid leukemia with translocation t(6;11)(q27;q23) in a VNTR rich region (see ST8) tumoral     --low   in tumors correlates with high tumor size and poor metastasis-free survival in patients tumoral     --low   in Pancreatic cancer constitutional   deletion     causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS