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FLASH GENE

Symbol

SPRED2

contributors: mct - updated : 24-11-2021

HGNC name	sprouty-related, EVH1 domain containing 2
HGNC id	17722

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	NNL4 Noonan-like 4
Location	2p14      Physical location : 65.537.985 - 65.659.656
Synonym name	sprouty protein with EVH-1 domain 2, related sequence
	sprouty-related protein with EVH-1 domain 2
Synonym symbol(s)	Spred-2, FLJ21897, FLJ31917, MGC163164

DNA

TYPE	functioning gene
STRUCTURE	121.60 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_181784 6 - 4457 NP_861449 47.6 418 - 2004 15184877 NM_001128210 6 - 4104 NP_001121682 47 415 - 2004 15184877

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 Homo sapiens Digestive mouth       highly   stomach       highly Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune lymph node       highly Reproductive male system prostate       Respiratory lung         Urinary kidney

cells

System Cell Pubmed Species Stage Rna symbol   fibroblast Lymhoid/Immune lymphocyte Lymphoid/Immune B cell Reproductive epithelial cell

cell lineage
cell lines
fluid/secretion	lymph

at STAGE

physiological period

fetal

Text	all fetal tissues

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a cys-rich domain responsible for the localization of the protein to the membrane ruffles
	one EVH1 domain (enabled/vasodilatator-stimulated phosphoprotein homology 1)

conjugated

Other

HOMOLOGY

Homologene

FAMILY

sprouty family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
text	in the cytoplasm in unstimulated cells but translocated to the membrane ruffles in cells stimulated with EGF(epidermal growth factor)

basic FUNCTION	may be functioning as an antagonist of fibroblast growth factor (FGF) pathways and may be negatively modulating respiratory organogenesis
	may be having an important function in chondrocytes and bone development
	modulate Ras-Raf interaction and MAP kinase signalling
	key regulator of RhoA-mediated cell motility and signal transduction
	SPRED1, SPRED2, SPRED3 modulate growth factor receptor signaling by inhibiting the RAS-MAPK cascade
	both SPRED1 and SPRED2 inhibit the ability of DYRK1A to phosphorylate its substrates
	likely involved in the regulation of dynamic developmental processes
	negative regulator of the hypothalamic-pituitary-adrenal axis
	SPRED2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK
	SPRED1, SPRED2 negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation
	is a novel, indispensable regulator of cardiac autophagy
	SPRED1, SPRED2 are required for the continuous embryonic growth and differentiation of the lens
	negative regulator of signaling elicited by cell-surface receptor tyrosine kinases

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	SPRED2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling
	direct and endogenous interaction of SPRED1 and SPRED2 with the novel kinase, DYRK1A (bind to a similar domain on DYRK1A as Tau, and possibly other substrates, and the hierarchy of binding will depend on the concentration of the competing proteins and the relative affinity for the DYRK1A-binding site)
	SPRED2 controls the development of LPS-induced lung inflammation by negatively regulating the ERK-MAPK pathway
	in wild-type hearts, SPRED2 interacted physically with SQSTM1, NBR1, and Cathepsin D, indicating that SPRED2 is required for autophagolysosome formation in regular autophagy

cell & other

REGULATION

repressed by	role for SPRED2 tyrosine phosphorylation and ubiquitination in controlling SPRED2 expression levels

ASSOCIATED DISORDERS

corresponding disease(s)

NNL4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function impairs autophagy, leading to cardiac dysfunction and life-threatening arrhythmias

Susceptibility

to rheumatoid arthritis (RA)

Variant & Polymorphism other	SPRED2 is an RA-susceptibility gene

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   SPRED2 may be a new therapeutic target for the treatment of ulcerative colitis (UC)

ANIMAL & CELL MODELS

	loss of Spred-2 inhibits bone growth by inhibiting chondrocyte differentiation through up-regulation of the MAPK signaling pathway
	Spred2(-/-) mice exhibit dwarfism and increase of early haematopoiesis
	Spred2-/-mice were reported to have a markedly reduced growth and shorter long bones,54 cardiac fibrosis and arrhythmias, and a shortened lifespan