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FLASH GENE

Symbol

SEMA3F

contributors: mct - updated : 30-10-2018

HGNC name	sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F
HGNC id	10728

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Cardiovascular heart         Digestive mouth       highly Endocrine thyroid       highly Lymphoid/Immune thymus         Homo sapiens Urinary kidney       highly Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular

cell lineage
cell lines	malignant lung cell lines
fluid/secretion	secreted

at STAGE

physiological period

fetal, pregnancy

Text	brain
	fetal eyes retina

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide, the SEMA domain containing about 14 cysteine residues with a RGD domain
	an Ig-like C2-type (immunoglobulin-like) domain
	a transmembrane domain (TM)
	a C terminal short basic domain

HOMOLOGY

interspecies	homolog to murine Sema3f (96.4pc)
	homolog to rattus Sema3f (95.8pc)

Homologene

FAMILY

semaphorin III family

CATEGORY

motor/contractile

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	repellent of the nerve growth cone guidance
	may play a role in cell motility and cell adhesion
	potent metastasis inhibitor that targets both tumor and stromal cells
	may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development (Hernández-Montiel 2008)
	had a repulsive effect on dopaminergic axons (Hernández-Montiel 2008)
	having a striking effect on tumor cell and EC morphology, causing cytoskeleton collapse, loss of stress fibers, loss of adhesion, and depolymerization of F-actin, rapidly within minutes
	axon guidance molecule, involved in TP53-regulated antiangiogenesis
	functions as an antiangiogenic factor that repels endothelial cells and compromises their proliferation/survival (Varshavsky 2008)
	can inhibit the binding of VEGF to neuropilin (Parker 2010)
	potent anti-angiogenic effects of Semaphorin 3F on both retinal and choroidal vessels
	functional role for Semaphorin 3F in the outer retina where it acts as a vasorepulsive cue to maintain physiologic avascularity
	SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions
	provides neuronal guidance cues via its ability to bind neuropilin 2 (NRP2) and Plexin A family molecules
	role in guiding axonal migration during neuronal development
	SEMA3A, -3C, and -3F, likely with coreceptors NRP1, NRP2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses

CELLULAR PROCESS	cell organization/biogenesis
	cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complex with NRP2 (neuropilin-2) and plexin A1
	NRCAM is a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the SEMA3F receptor complex

INTERACTION

DNA

RNA

small molecule

protein	FMR1 (RNA target of FMR1)
	neuropilin-2 (NRP2) agonist (functional receptor for SEMA3F)
	interacting with SEMA3A (combinations of SEMA3A and SEMA3F may be able to inhibit tumor angiogenesis more effectively than single semaphorins)
	interacting with TP53 (TP53-binding sequence in intron 1 of SEMA3F interacts with TP53 and has a TP53-responsive transcriptional activity, negatively regulating tumor vessel formation and cell growth)
	interacting with ID2 (SEMA3F, a potent inhibitor of metastasis, was repressed by ID2)
	hypoxia induces tumor and endothelial cell migration in a SEMA3F- and VEGFA-dependent manner via transcriptional repression of their common receptor NRP2
	SEMA3F can induce CHN2 activation and CHN2 is required for SEMA3F-dependent inhibition of Rac-GTP levels and does not significantly affect levels of activated CDC42
	SEMA3F can down-regulate TP53 expression in primary hippocampal neurons, thereby contributing to growth cone collapse
	PLXNA3 is involved in SEMA3F-mediated oligodendrocyte precursor cell migration
	SEMA3F regulates MTOR signaling in diverse human cell types, suggesting that it has broad therapeutic implications.
	SEMA3F functions as an unconventional SEMA3 that promotes extraembryonic angiogenesis by inhibiting the MYC-regulated synthesis of THBS1 in visceral yolk sac epithelial cells
	NRCAM mediate spine pruning as a subunit of the receptor complex for the repellent ligand SEMA3F
	NRCAM stabilizes binding between NRP2 and PLXNA3 necessary for SEMA3F-induced spine pruning

cell & other

REGULATION

activated by

histone deacetylase inhibition

repressed by

promoter methylation

Other

proteolytically processed by FURIN (Parker 2010)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in metastatic tumor tumoral     --low   in lung cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	semaphorin 3F amniotic level at 16-18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy
Therapy target
	System Type Disorder Pubmed neurosensorial visual degenerative use of SEMA3F in protecting the outer retina against subretinal neovascularization.

ANIMAL & CELL MODELS