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FLASH GENE

Symbol

GRB10

contributors: mct/pgu - updated : 13-10-2013

HGNC name	growth factor receptor-bound protein 10
HGNC id	4564

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	203.40 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	subject to alternative splicing of the 5prime exons, many of which are non-coding (PMID: 19487367)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005311 GRB10 gamma 16 - 4713 68 594 biallelic, paternally expressed only in the brain 2010 19487367 a potential SH3 binding sequence, PH and SH2 domains NM_001001549 alpha GRB-IR 15 - 4575 60 548 skeletal muscle, pancreas 2010 19487367 a truncated PH domain NM_001001550 GRB10 beta 16 - 4793 50 536 skeletal muscle, pancreas, biallelic, paternally expressed only in the brain 2010 19487367 NM_001001555 17 - 5040 - 605 biallelic, paternally expressed only in the brain 2010 19487367 a third alternative N terminal, a PH domain GRB10 epsilon or KIAA0207 GRB10 zeta - - 1849 - 594 paternally expressed only in the brain 2010 19487367 GRB10 t - - 2629 - 694 testicular 2010 19487367

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 esophagus       highly Endocrine pancreas       highly   thyroid       highly Nervous brain         Reproductive male system testis       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

IMPRINTING	maternally
text	in fetal brain
	maternal allele-specific expression is conserved only in the placental villous trophoblasts, an essential part of the placenta involved in nutrient transfer
	predominantly expressed from the maternal allele during embryogenesis

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal proline-rich region,
	a Ras-GTPase binding domain,
	a PH domain,
	an SH2 domain and a BPS domain in between the PH and SH2 domains
	C terminal SH2 domain

HOMOLOGY

interspecies

homolog to murine Grb10

Homologene

FAMILY

GRB7/10/14 family

CATEGORY

adaptor , regulatory , signaling , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	involved in signal transduction in developing embryos
	regulating cell proliferation and apoptosis
	signalling adapter protein, expressed predominantly from the maternally-inherited allele and acting to restrict foetal and placental growth
	can influence reproductive strategy through the allocation of maternal resources such that offspring number is offset against size
	might act as a connector, bringing NEDD4 close to IGF1R to facilitate the ubiquitination of IGF1R by NEDD4
	unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues
	intracellular adaptor protein that acts as a negative regulator of insulin and insulin-like growth factor 1 (IGF1) receptors
	might be a tumor suppressor regulated by MTOR
	influences fetal growth, adult behavior and tumor formation
	intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1 (IGF1), and negatively regulates their actions
	may act as a negative regulator of myogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	RET, IGF1R, GHR, INSR
	binding insulin and IGF receptors
	binds to the intracellular portion of LRP6 and negatively regulates Wnt signaling, by interfering with the binding of Axin to LRP6
	interacts with BCL2L11 and inhibits its proapoptotic activity in a phosphorylation-dependant manner
	can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its Src homology 2 (SH2) domain
	MTOR-mediated phosphorylation stabilized GRB10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K)
	LMX1A is an activator of RGS4 and GRB10 and is responsible for the correct specification of rostral and medial mesodiencephalic dopamine (mdDA) neurons

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SRS7

Susceptibility

Variant & Polymorphism

Candidate gene	candidate for growth disturbance disorders
Marker
Therapy target

ANIMAL & CELL MODELS

	adult mice deficient in Grb10 have elevated body mass and muscle mass throughout adulthood, up to 12 mo of age, and grb10 plays a previously unrecognized role in regulating the development of fiber number during murine embryonic growth
	Grb10(-/-) mice exhibit improved whole body glucose homeostasis and an increase in muscle mass associated specifically with an increase in myofiber number