SPRED1

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.

Function

Spread-1 is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade.

Clinical associations

Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS).

Mutations in this gene are associated with

• Legius syndrome.
• Childhood leukemia

Mutations

The following mutations have been observed:

• An exon 3 c.46C>T mutation leading to p.Arg16Stop. This mutation may result in a truncated nonfunctional protein. Blast cells analysis displayed the same abnormality as germline mutation with one mutated allele (no somatic SPRED1 single-point mutation or loss of heterozygosity was found). The M4/M5 phenotype of AML are most closely associated with Ras pathway mutations. Ras pathway mutations are also associated with monosomy 7.
• 3 Nonsense (R16X, E73X, R262X)
• 2 Frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp)
• Missense (V44D)
• p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.

Disease Database

SPRED1 gene variant database

See also

• Neurofibromin 1
• Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations.

Further reading

• Batz C, Hasle H, Bergsträsser E, van den Heuvel-Eibrink MM, Zecca M, Niemeyer CM, Flotho C (March 2010). "Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?" (PDF). Blood. 115 (12): 2557–8. doi:10.1182/blood-2009-12-260901. PMID 20339110.
• Lock P, I ST, Straffon AF, Schieb H, Hovens CM, Stylli SS (December 2006). "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination". Biochemical and Biophysical Research Communications. 351 (4): 1018–23. doi:10.1016/j.bbrc.2006.10.150. PMID 17094949.
• Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, Ballerini P, Cartault F, Barbarot S, Landman-Parker J, Soufir N, Parfait B, Vidaud M, Wolkenstein P, Vidaud D, France RN (July 2009). "SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype". Journal of Medical Genetics. 46 (7): 425–30. doi:10.1136/jmg.2008.065243. PMID 19366998.
• Nonami A, Taketomi T, Kimura A, Saeki K, Takaki H, Sanada T, Taniguchi K, Harada M, Kato R, Yoshimura A (September 2005). "The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1". Genes to Cells. 10 (9): 887–95. doi:10.1111/j.1365-2443.2005.00886.x. PMID 16115197.
• Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biology. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Chandramouli S, Yu CY, Yusoff P, Lao DH, Leong HF, Mizuno K, Guy GR (January 2008). "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling". The Journal of Biological Chemistry. 283 (3): 1679–91. doi:10.1074/jbc.M705457200. PMID 17974561.
• Johne C, Matenia D, Li XY, Timm T, Balusamy K, Mandelkow EM (April 2008). "Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton". Molecular Biology of the Cell. 19 (4): 1391–403. doi:10.1091/mbc.E07-07-0730. PMC 2291396. PMID 18216281.
• Nonami A, Kato R, Taniguchi K, Yoshiga D, Taketomi T, Fukuyama S, Harada M, Sasaki A, Yoshimura A (December 2004). "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells". The Journal of Biological Chemistry. 279 (50): 52543–51. doi:10.1074/jbc.M405189200. PMID 15465815.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E (September 2007). "Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype". Nature Genetics. 39 (9): 1120–6. doi:10.1038/ng2113. PMID 17704776.
• Yoshida T, Hisamoto T, Akiba J, Koga H, Nakamura K, Tokunaga Y, Hanada S, Kumemura H, Maeyama M, Harada M, Ogata H, Yano H, Kojiro M, Ueno T, Yoshimura A, Sata M (October 2006). "Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors". Oncogene. 25 (45): 6056–66. doi:10.1038/sj.onc.1209635. PMID 16652141.
• King JA, Straffon AF, D'Abaco GM, Poon CL, I ST, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM (June 2005). "Distinct requirements for the Sprouty domain for functional activity of Spred proteins". The Biochemical Journal. 388 (Pt 2): 445–54. doi:10.1042/BJ20041284. PMC 1138951. PMID 15683364.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S (October 2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.