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FLASH GENE

Symbol

FYN

contributors: mct/npt/pgu - updated : 17-08-2018

HGNC name	FYN oncogene related to SRC, FGR, YES
HGNC id	4037

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	212.14 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002037 14 - 2650 NP_002028 60 537 - 2010 19733625 a 14 exons variant lacking exons 4 and 11 encoding for the longest product NM_153047 11 splicing 2073 NP_694592 60 534 - 2010 19733625 an 11 exons variant lacking exons 1, 2, 3 and 4 NM_153048 11 splicing 2000 NP_694593 54.4 482 - 2010 19733625 a 11 exons variant lacking exons 1, 2, 3, 10 and 11 encoding for the shortest product

EXPRESSION

Type

widely

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 Digestive pharynx       moderately Endocrine thyroid       highly Lymphoid/Immune spleen       highly   thymus       moderately Nervous brain       moderately   nerve       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Nervous oligodendrocyte Homo sapiens Reproductive oocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	embryonic tissue

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a Src homolgy 2, a Src homology 3 domains
	a K homology (KH) motif bound to a QUA2 motif (RNA binding)
	a proteine kinase catalytic domain

HOMOLOGY

interspecies	homolog to rattus Fyn (99.63 pc)
	homolog to murine Fyn (94.19 pc)

Homologene

FAMILY	Src-family tyrosine kinases
	Tyr protein kinase family
	SRC subfamily (signal transduction)
	STAR (signal transduction and activator of RNA) family

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	non receptor tyrosine kinase, involved in T cell signaling regulation
	also involved in protocadherin signaling
	monopalmitoylated SFK required for VEGF mitogenic signaling with SRC and FYN, but maintaining distinct properties in the regulation of VEGF-mediated endothelial cell events
	implicated in both brain development and adult brain function
	in mast cell degranulation in interacting with both cytosolic and structural proteins
	involved in mast cell degranulation in interacting with both cytosolic and structural proteins
	may play an important role in HTR6- mediated signaling pathways in the central nervous system
	involved in tyrosine phosphorylation of KIRREL (results in significantly increased KIRREL and TJP1 binding, suggesting a critical role for KIRREL tyrosine phosphorylation in reorganizing the KIRREL-TJP1 complex)
	mediates chronic myelogenous leukemia cell proliferation
	in part through its effects on DAB1, regulates the phosphorylation, trafficking, and processing of APP and LRP8
	playing a role in exit from meiotic and mitotic metaphases and required for regulation of microtubules polymerization and spindle stabilization
	play an essential role in signaling events that implicate spindle assembly checkpoint pathway and hence in regulating the exit from metaphase in oocytes and zygote
	plays a key role in oligodendrocyte differentiation and myelination in the central nervous system
	is an important signaling molecule in oligodendrocytes
	FYN cooperates with oncogenic FLT3-ITD in cellular transformation by selective activation of the STAT5 pathway
	MAGI2 and FYN protect DDN from NEDD4L-mediated ubiquitination and from nuclear translocation, thereby maintaining the physiologic homeostasis of podocytes, and the lack of MAGI2 in podocytes results in glomerulosclerosis

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	ATP
	Mn2+

protein	the cytoplasmic tail of protocadherins
	ADD2 (colocalizing under plasma membranes)
	binding to vimentin and pyruvate kinase
	complexed with staurosporine
	ARHGAP33 is a novel FYN substrate
	interacting with brain-specific PTPRT (PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase FYN)
	PTPRA is an important positive regulator of FYN activation and signaling that is required for the differentiation of oligodendrocyte progenitor cells (OPCs)
	interaction with FYB, a FYN adapter protein expressed in podocytes, and TMEM47 possibly through FYB, may regulate FYN activity
	SLIT2 regulates the dispersal of oligodendrocyte precursor cells through FYN and RHOA signaling
	NCK1 directly modulates NPHS1 phosphorylation through formation of a signaling complex with the Src family kinase FYN
	functional interaction between FYN, AGAP2, and STAT5A in mediating adipogenesis
	UNC119 plays a key role in the FYN signal transduction pathway, which regulates the completion of cytokinesis via RAB11A
	dynamic interaction between CAMK2D2 and FYN in VSM (Vascular smooth muscle) cells, indicating a mechanism by which CAMK2D2 and FYN may coordinately regulate VSM cell motility
	SH2D1a plays an essential role in collagen-induced arthritis (CIA) because of FYN-independent and FYN-dependent effects on follicular T helper (TFH) cells and, possibly, other T cell types
	MOBP levels are regulated by FYN kinase and affect the morphological differentiation of oligodendrocytes
	DDN is phosphorylated by FYN and dephosphorylated by PTPN1, and FYN-induced phosphorylation prevents NEDD4L-mediated ubiquitination of dendrin
	FYN has likely a regulatory role in NOS2 expression in astrocytes during neuroinflammatory responses

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function activated in clear cell renal carcinoma with good outcome tumoral     --over   in chronic myelogenous leukemia blast crisis compared with chronic phase

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	therapies targeting Fyn expression for chronic myelogenous leukemia

ANIMAL & CELL MODELS