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FLASH GENE

Symbol

SEMA3C

contributors: mct/npt - updated : 30-10-2017

HGNC name	sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C
HGNC id	10725

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 Cardiovascular heart       highly Digestive intestine large intestine colon   highly   intestine small intestine     highly Reproductive female system breast mammary gland   highly   female system ovary     highly   male system testis     highly   male system prostate     highly Respiratory respiratory tract trachea     highly Urinary bladder       highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	in the developing nervous system

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 motif
	a psi domain
	a C terminal short basic domain

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

semaphorin family

CATEGORY

immunity/defense

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	secreted

basic FUNCTION	may be involved in diverse cell survival mechanisms
	repellent of the nerve growth cone guidance
	may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development (Hernández-Montiel 2008)
	had an attractive effect and enhanced axon growth (Hernández-Montiel 2008)
	neurovascular guiding molecule, regulated directly by GATA6 (Kodo 2009)
	promoting the migration of breast cancer cells after activation by ADAMTS1 (Esselens 2010)
	is essential for setting stereotyped motor tract positioning in limb-derived chemotropic semaphorins
	SEMA3C constitutes an adipocyte-derived paracrine signal that influences extracellular matrix (ECM) composition and may play a pathophysiological role in white adipose tissue (WAT)
	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
	promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells
	SEMA3C promotes migration, invasion and cell dissemination
	SEMA3C is a secreted semaphorin that plays an important role in the maintenance of cancer stem-like cells, promotes migration and invasion, and may facilitate angiogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

SEMA32C/SEMA3D signaling is an evolutionarily conserved regulator of enteric nervous system (ENS) development whose dys-regulation is a cause of enteric aganglionosis

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with GATA6 (SEMA3C and PLXNA2 are directly regulated by GATA6 through consensus binding sites on their enhancer elements and GATA6 mutations disturbs semaphorin-plexin signaling to varying degrees, resulting in abnormal development of the cardiac outflow tract)(Kodo 2009)
	ligand of receptor plexin A2 (PLXNA2)(Kodo 2009)
	motoneuronal SEMA3C regulates the shared SEMA3 neuropilin receptors NRP1 and NRP2 levels in opposite ways at the growth cone surface
	axonal guidance cue SEMA3C promotes normal alveolar growth
	neural crest-derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation
	FOXA1 is a negative regulator of SEMA3C and SEMA3C is a novel target of AR, GATA2, and FOXA1
	SEMA3C drives activation of multiple RTKs including EGFR, ERBB2, and MET in a cognate ligand-independent manner via PLXNB1

cell & other

REGULATION

activated by

cleavage by ADAMTS1, and thus contributing to the metastatic program (Esselens 2010)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in the synovial tissue of rheumatoid arthritis and osteoarthritis tumoral     --other   aberrant expression of SEMA3C is correlated with poor prognosis of pancreatic ductal adenocarcinoma (PDAC) patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS