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FLASH GENE

Symbol

FES

contributors: mct - updated : 07-12-2001

HGNC name	feline sarcoma oncogene
HGNC id	3657

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	11.34 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	promoter methylation is an important mechanism responsible for downregulation of FES gene expression in colorectal cancer cells (Shaffer 2009)

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D15S95 - D15S111 - BLM - D15S127 - FURIN - FES- D15S158 - D15S100 - D15S107 - IGF1R - D15S87 - qter
Authors	Butler (94), Ellis (95)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002005 19 - 2783 NP_001996 93.3 822 - 2010 20117079 isoform 1 NM_001143783 17 - 2513 NP_001137255 86.5 764 - 2010 20117079 variant 2 lacks an in-frame exon in the 5' coding region isoform 2 NM_001143784 17 - 2477 NP_001137256 85.33 752 - 2010 20117079 variant 3 lacks an in-frame exon in the 3' coding region isoform 3 NM_001143785 17 - 2422 NP_001137257 78.5 694 - 2010 20117079 variant 4 lacks multiple in-frame exons in the coding region isoform 4

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 Lymphoid/Immune spleen       highly   thymus       highly Respiratory respiratory tract trachea     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a unique N-terminal region
	two coiled-coil (CC) domains (CC1 and CC2) critical regulators of Fes activity and that may function to recruit Fes activators and/or substratesa FCH domain
	a protein kinase domain
	a SH2 domain

HOMOLOGY

interspecies	homolog to Fujinami avian sarcoma viral (v-fps) oncogene
	homolog to murine Fes (90.6pc)
	homolog to rattus Fes (91.5pc)

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	Fes/fps subfamily

CATEGORY

enzyme , tumor suppressor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	having tyrosine-specific protein kinase activity, required for maintenance of cellular transformation
	implicated in the differentiation of a number of cell types including neuronal, endothelial and myeloid cells
	tumor suppressor gene in colorectal cancer (Shaffer 2009)
	required for KITLG-induced chemotaxis, mediator of KIT signalling implicated in cell migration (Voisset 2010)
	implicated in regulating cross-talk between KIT and beta1 integrins to promote cytoskeletal reorganization and motility of mast cells
	is an SH2-containing tyrosine kinase protein, and this domain enhances catalytic activity and substrate recognition
	PLD2 and FES might be physically associated, which could be beneficial for a quick transduction of the activating signal within the cell

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

new signaling pathway (JAK-FES-PLD2) that is enhanced in highly proliferative breast cancer cells

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with TRIM28 (FES-TRIM28 interaction, with a dual role for TRIM28 as both a FES activator and downstream effector)
	interacting with KIT (Voisset 2010)
	JAK3, FES and PLD2 interactions in transformed cells maintain PLD2 at an enhanced level that leads to abnormal cell growth

cell & other

REGULATION

Other

phosphorylated following KIT activation by its ligand KITLG (Voisset 2010)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in colon tumor and colorectal cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast its inhibition might provide therapeutic benefits in breast cancer, in part by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages

ANIMAL & CELL MODELS