SPRY2 Knowpia

SPRY2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3BUM, 3OB1
Identifiers
Aliases	SPRY2, hIGAN3, sprouty RTK signaling antagonist 2
External IDs	OMIM: 602466 MGI: 1345138 HomoloGene: 4267 GeneCards: SPRY2
Gene location (Human)
Chr.	Chromosome 13 (human)
End	80,341,126 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	106,134,253 bp
RNA expression pattern
	Top expressed in
	tibial nerve; ; left uterine tube; ; pericardium; ; parotid gland; ; right lung; ; right ventricle; ; retinal pigment epithelium; ; cerebellar vermis; ; subcutaneous adipose tissue; ; left coronary artery;
	Top expressed in
	primary motor cortex; ; morula; ; cingulate gyrus; ; blastocyst; ; lateral geniculate nucleus; ; retinal pigment epithelium; ; olfactory tubercle; ; internal carotid artery; ; amygdala; ; superior frontal gyrus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein serine/threonine kinase inhibitor activity; protein serine/threonine kinase activator activity; protein binding; protein kinase binding;
Cellular component	cytoplasm; cytosol; cell projection; membrane; plasma membrane; ruffle membrane; microtubule; cytoskeleton; nucleus; microtubule cytoskeleton;
Biological process	cell fate commitment; negative regulation of neurotrophin TRK receptor signaling pathway; positive regulation of protein kinase B signaling; negative regulation of epidermal growth factor receptor signaling pathway; lung morphogenesis; lung development; bud elongation involved in lung branching; negative regulation of peptidyl-threonine phosphorylation; lung growth; negative regulation of apoptotic process; sensory perception of sound; positive regulation of peptidyl-serine phosphorylation; negative regulation of Ras protein signal transduction; multicellular organism development; negative regulation of fibroblast growth factor receptor signaling pathway; positive regulation of gene expression; negative regulation of GTPase activity; regulation of cell population proliferation; regulation of signal transduction; negative regulation of MAP kinase activity; inner ear morphogenesis; respiratory system development; establishment of mitotic spindle orientation; negative regulation of cell projection organization; positive regulation of ERK1 and ERK2 cascade; regulation of cell differentiation; branching morphogenesis of an epithelial tube; negative regulation of cell population proliferation; positive regulation of protein serine/threonine kinase activity; positive regulation of cell migration; negative regulation of ERK1 and ERK2 cascade; cellular response to leukemia inhibitory factor; negative regulation of angiogenesis; cellular response to vascular endothelial growth factor stimulus; negative regulation of vascular endothelial growth factor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	10253
	24064
	ENSG00000136158
	ENSMUSG00000022114
	O43597
	Q9QXV8
	NM_005842; NM_001318536; NM_001318537; NM_001318538
	NM_011897
	NP_001305465; NP_001305466; NP_001305467; NP_005833
	NP_036027
	Wikidata
View/Edit Human	View/Edit Mouse

Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene.^[5]

Function edit

This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein.^[6]

SPRY2 is a negative feedback regulator of multiple receptor tyrosine kinases (RTKs) including receptors for fibroblast growth factor (FGF),^[5] epidermal growth factor (EGF),^[7] and hepatocyte growth factor (HGF).^[8] Antagonization of growth factor mediated pathways, cell migration, and cellular differentiation occurs through the ERK pathway.^[7] Spry2 can also enhance EGFR signaling by sequestering CBL. Spry gene expression has been reported silenced or repressed in cancer of the breast, liver, lung, prostate,^[7] and in lymphoma.^[9] Human spry2 expression is localized to the microtubules in unstimulated cells.^[10] All sprouty isoforms inhibit the ERK pathway by themselves, but can also form heterodimers and homodimers which have enhanced inhibition.^[10]

Interactions edit

SPRY2 has been shown to interact with Cbl gene.^[11]^[12]^[13]

References edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000136158 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022114 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow MA (January 1998). "sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways". Cell. 92 (2): 253–63. doi:10.1016/S0092-8674(00)80919-8. PMID 9458049.
^ "Entrez Gene: SPRY2 sprouty homolog 2 (Drosophila)".
^ ^a ^b ^c Frank MJ, Dawson DW, Bensinger SJ, Hong JS, Knosp WM, Xu L, Balatoni CE, Allen EL, Shen RR, Bar-Sagi D, Martin GR, Teitell MA (March 2009). "Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas". Blood. 113 (11): 2478–87. doi:10.1182/blood-2008-05-156943. PMC 2656273. PMID 19147787.
^ Lee CC, Putnam AJ, Miranti CK, Gustafson M, Wang LM, Vande Woude GF, Gao CF (July 2004). "Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis". Oncogene. 23 (30): 5193–202. doi:10.1038/sj.onc.1207646. PMID 15122328. S2CID 56279.
^ Sánchez A, Setién F, Martinez N, Oliva JL, Herranz M, Fraga MF, Alaminos M, Esteller M, Rojas JM (August 2008). "Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas". Oncogene. 27 (36): 4969–72. doi:10.1038/onc.2008.129. PMID 18427547. S2CID 19450976.
^ ^a ^b Bundschu K, Walter U, Schuh K (December 2006). "The VASP-Spred-Sprouty domain puzzle". The Journal of Biological Chemistry. 281 (48): 36477–81. doi:10.1074/jbc.R600023200. PMID 16987806.
^ Wong ES, Lim J, Low BC, Chen Q, Guy GR (February 2001). "Evidence for direct interaction between Sprouty and Cbl". The Journal of Biological Chemistry. 276 (8): 5866–75. doi:10.1074/jbc.M006945200. PMID 11053437.
^ Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY, Guy GR (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". The EMBO Journal. 21 (18): 4796–808. doi:10.1093/emboj/cdf493. PMC 126289. PMID 12234920.
^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (March 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". The EMBO Journal. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061.