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FLASH GENE

Symbol

SOS1

contributors: mct - updated : 28-04-2016

HGNC name	son of sevenless homolog 1 (Drosophila)
HGNC id	11187

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	GINGF gingival fibromatosis NS4 Noonan syndrome 4
Location	2p22.1      Physical location : 39.208.691 - 39.347.604
Synonym name	alternate SOS1
	guanine nucleotide exchange factor
	RAS guanine nucleotide-exchange factor (RAS-GEF)
Synonym symbol(s)	GF1, HGF, GGF1, SOS

DNA

TYPE	functioning gene
STRUCTURE	138.91 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005633 23 - 8331 NP_005624 - 1333 - 2007 17586837

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 Digestive mouth gingiva     highly Lymphoid/Immune lymph node       highly Reproductive female system uterus cervix   highly   female system breast mammary gland   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one N-terminal RAS GEF domain (RAS exchanger motif REM), a helical PH-REM linker motif, and a histone folds (HF) domain with a basic surface that binds membrane phospholipids, and membrane recognition by the HF domain plays a functional role in primitive endoderm (PrE) specification
	one DBL-homology domain (DH)
	one PH domain
	a CDC25 and polyproline domains
	GRB2 binding sites, inside the C-terminal region responsible for regulation of activity

HOMOLOGY

interspecies

homolog to Drosophila son of sevenless,1

Homologene

FAMILY

CATEGORY

regulatory , protooncogene , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome,nucleosome

basic FUNCTION	GDP-GTP exchange factor
	promoting the exchange of RAS-bound GDP by GTP
	Ras nucleotide exchange-factor promoting nucleotide exchange and thus Ras activation, leading to Erk and Jnk activation alone or in association with GRB2
	Rac1 activation,causing Jnk activation alone in complex with Eps8 and E3b1 ,
	not being a significant oncogene in most cancers
	have a surprising negative role for ABL kinases in CRK transformation
	was required for pre-T-cell receptor (pre-TCR)- but not TCR-stimulated developmental signals
	is uniquely positioned to affect signal transduction early in thymocyte development
	multi-domain protein that plays a major role in cell growth and differentiation through its Ras-specific guanine nucleotide exchange domain whose complex regulation involves intra-molecular, inter-domain rearrangements
	is a dual guanine nucleotide exchange factor (GEF) that activates the guanosine triphosphatases RAC1 and RAS, which mediate signaling initiated by peptide growth factors
	RASGRP1 and GRB2/SOS1 are insulators of signals that lead to RAS activation induced by different stimuli, rather than cooperating downstream of the TCRA
	SOS1 and its adaptor GRB2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway during development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage
	RASGRP1 and SOS1 are RAS-specific nucleotide exchange factors that have distinct roles in lymphocyte development
	SOS1 and SOS2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases
	functional redundancy between SOS1 and SOS2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes
	SOS1 and SOS2 are ubiquitously expressed Ras-guanine exchange factors involved in Erk-MAP kinase pathway activation
	essential role of SSOS1, SOS2 proteins in cellular proliferation and migration

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

text	control of cell proliferation

PATHWAY

metabolism

signaling

signal transduction

is a functional component of the pathway connecting EGFR to NFKB1 activation

a component

INTERACTION

DNA

RNA

small molecule

protein	GRB2
	interacts with phosphorylated LAT2
	SH3PXD2A binding partner
	in addition to its GEF activity, SOS1 acted as a scaffold to nucleate oligomerization of the T cell adaptor protein LAT (linker for activation of T cells)
	scaffold function of SOS1 depended on its ability to bind to the adaptor protein GRB2
	regulates sustained TCR-mediated Erk activation
	physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on RAS, which prevents the epidermal growth factor (EGF)-induced activation of the RAS–ERK1/2 pathway
	RASGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-RAS signals in colorectal carcinoma cells

cell & other

REGULATION

repressed by

GRB2 (mediate negative regulation of the intrinsic Ras guanine-nucleotide exchange activity)

ASSOCIATED DISORDERS

corresponding disease(s)

GINGF , NS4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation   --other   SOS1p.R497Q variant modifier constitutional     --other   dysfunction (expression) of the FGFR1, SOS1 and RAF1 genes is involved in the development of unilateral or bilateral cryptorchidism

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate potential candidate biomarker and molecular therapeutic target in prostate cancer

ANIMAL & CELL MODELS