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FLASH GENE

Symbol

GAS6

contributors: mct/npt - updated : 25-01-2016

HGNC name	growth arrest-specific 6
HGNC id	4168

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000820 15 - 2521 NP_000811 - 678 - 2007 17174935 NM_001143945 9 - 2188 NP_001137417 - 405 - 2007 17174935 NM_001143946 7 - 2523 NP_001137418 - 379 - 2007 17174935

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 Digestive liver         Nervous brain           nerve       highly   nerve cranial nerve     highly Reproductive female system uterus     highly Respiratory lung

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens Blood/Hematopoietic platelet Cardiovascular endothelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four EGF-like domains and gamma carboxylglutamic residues (GLA domain)
	two laminin A/neurexin/sex hormone-binding globulin repeats (LNS)
	one GAS specific domain

isoforms

Precursor

proteolytically processed in two secreted fragments, a 30 kDa N terminal and a 50 kDa C terminal protein

HOMOLOGY

interspecies

homolog to murine Gas6

intraspecies

paralog to PROS1

Homologene

FAMILY

vitamin K-dependent family of protein

CATEGORY

regulatory , secretory , signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus

basic FUNCTION	vitamine-K dependent protein involved in the stimulation of cell proliferation, cell growth and survival, cell adhesion and migration
	estrogen target gene in mammary epithelial cells
	may be one of the factors involved in the estrogen-stimulated ductal growth of mammary glands
	GAS6/AXL-mediated signaling regulates dendritic cell activities, and identifies GAS6/AXL as a new dendritic cell chemotaxis pathway (Scutera 2009)
	GAS6 synthesis is likely to be a regulatory mechanism during systemic inflammation
	is an important regulator of both CNS demyelination and remyelination
	Vitamin K-dependent protein GAS6 playing a role in vascular smooth muscle cell (VSMC) survival and migration, as well as in endothelium and leukocyte activation, and that could therefore be involved in atherosclerosis
	acts as a protective factor, in part by reducing the pro-inflammatory phenotype of VSMC
	implicated in both anti-inflammatory response as well as platelet/leukocytes activation
	increased tissue factor mRNA and protein expression in endothelial cells
	key regulator of the vascular system, which is linked to a number of cardiovascular diseases
	likely activates the AKT1 signaling pathway, which, in turn, promotes the proliferation and migration of endothelial progenitor cells (EPCs)
	cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix
	vitamin K-dependent protein involved in cell survival, migration, and proliferation in response to inflammatory processes
	may represent a novel independent risk factor for primary Sjögren syndrome (pSS), with a potential role in salivary gland inflammation and dysfunction

CELLULAR PROCESS	cell life, proliferation/growth
	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

coagulation/hemostasis

text	enhancing platelet degranulation and aggregation responses through its receptors promoting platelet activation and mediating thrombus formation

PATHWAY

metabolism

signaling

	GAS6/AXL signaling plays an important role in vascular biology by modulating survival and migration of vascular smooth muscle cells and endothelial cells (Li 2009)
	GAS6/AXL signaling is essential for delaying the cellular senescence process regulated by the PI3K/AKT1/FOXO1 signaling pathway

a component

INTERACTION

DNA

RNA

small molecule
	Ca++ binding

protein	ligand for TYRO3/AXL ,SKY and MER family of receptor tyrosine kinases
	GAS6 in circulation is bound to AXL suggesting circulating GAS6 to be inhibited and incapable of stimulating the TAM receptors
	THBD is a novel molecule that promotes apoptosis and vascular calcification by regulation of GAS6, presumably via EGF receptor/ERK axis
	interact with AXL in endothelial cells, inducing several signaling pathways involved in cell survival and proliferation
	GAS6-induced AXL signaling is a critical driver of pancreatic cancer progression
	GAS6-FOXO1 signaling axis plays an important role in VCAM1 expression in the context of venous thromboembolism (VTE)

cell & other

REGULATION

inhibited by

estrogen in ER positive breast cancer cells

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in both glioma and vascular cells and predict poor prognosis in glioblastoma multiformis patients (Hutterer 2008) constitutional     --over   in patients with RPL (recurrent pregnancy loss) constitutional     --over   in systemic lupus erythematosus, with lupus nephritis or cutaneous vasculitis constitutional     --over   GAS6 serum concentrations are significantly increased in Preeclampsia (PE) during pregnancy constitutional     --over   associated with venous thromboembolic disease

Susceptibility

to atherothrombotic disease

Variant & Polymorphism SNP	SNP c834+7G>A in intron 8 increasing the risk of atherothrombotic disease

Candidate gene
Marker	potential to serve as a SLE disease activity marker
Therapy target
	System Type Disorder Pubmed cancer endocrine thyroid TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells and targeting the circuit could offer a novel therapeutic approach in this cancer cancer brain glioma/neuroblstoma specific targeting of the Axl/Gas6 signaling pathway may represent a potential new approach for glioma treatment cancer digestive colon unique inhibitory role during the progression of intestinal tumors associated with suppression of stromal immune reactions, suggesting a novel therapeutic approach for colorectal cancer patients cancer endocrine pancreas GAS6 inhibition with low-dose warfarin or other AXL-targeting agents may improve outcome in patients with AXL-expressing tumors

ANIMAL & CELL MODELS