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FLASH GENE

Symbol

SEMA4D

contributors: mct/npt - updated : 03-11-2015

HGNC name	sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
HGNC id	10732

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

constitutive of

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 intestine large intestine colon   highly Endocrine adrenal gland       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Lymphoid         Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Lymphoid/Immune B cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	embryonic dorsal root ganglion (DRG) neurons

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide
	the SEMA domain containing about 14 cysteine residues
	an Ig-like domain,
	a single transmembrane segment
	a C terminal short cytoplasmic tail

HOMOLOGY

Homologene

FAMILY

semaphorin family

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm

basic FUNCTION	repellent of the nerve growth cone guidance
	inducing B cell to aggregate and improving their viability in vitro
	promotes angiogenesis, invasive growth, proliferation, and antiapoptosis of cancer cells (Ch'ng 2007)
	stimulating axonal outgrowth of embryonic dorsal root ganglion (DRG) neurones in stead of retraction
	in platelets, has roles in the response to vascular injury, is able to interact directly with receptors on nearby platelets, promoting thrombus formation on exposed collagen (Zhu 2007)
	acting as a chemorepellant to the axons of retinal ganglion cells and hippocampal neurons (Fuchikawa 2009)
	PTPN11-mediated tyrosine dephosphorylation is an important step in SEMA4D-induced axon repulsion (Fuchikawa 2009)
	signaling requires the recruitment of PLC gamma into the PLXNB1 receptor complex (Swiercz 2009)
	SEMA4D/PLXNB1 promotes the dephosphorylation and activation of PTEN through the RRas GAP activity, inducing growth cone collapse
	SEMA4D/PLXNB1-mediated NFKB1 activation and IL8 production is critical in the generation a pro-angiogenic phenotype in endothelial cells
	role for PPLXNB1 in maintenance of melanocyte survival and proliferation in the skin, suggesting that SEMA4D and PLXNB1 act cooperatively with HGF and MET to regulate MET-dependent effects in human melanocytes
	is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation
	PLXNB1 and SEMA4D cooperate to promote perineural invasion in a RHOA/ROK-dependent manner
	plays a role in tumor-induced angiogenesis similar to vascular endothelial growth factor VEGFA

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	ligand for plexin B1 (PLXN4), and CD72
	binding to PLXNB1 and subsequently stimulating the interaction between PLXNB1 and RAC1
	enhances tumor cell motility through binding its receptor, PLXNB1, in pancreatic cancer
	SEMA4D/PLXNB1-mediated MRAS GAP activity regulates actin-based dendrite remodeling through RAPH1
	act through its receptor PLXNB1 to regulate axon growth cone guidance, lymphocyte activation, and bone density
	STING1 activates ADAM17 and this activation produces soluble proinflammatory SEMA4D independently of the TBK1/IRF3-mediated transcriptional pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in patients with thrombotic disorders or on cardiac bypass tumoral     --over   in soft tissue sarcoma with poorer overall and disease-free survival (Ch'ng 2007)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     targeting SEMA4D function along with VEGFA could represent a novel anti-angiogenic therapeutic strategy for the treatment of solid tumors.

ANIMAL & CELL MODELS