SPRED1
Sprouty-related, EVH1 domain-containing protein 1 (Spred-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.[1]
Function
Spred-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.[1]
Clinical associations
Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS).[1]
Mutations in this gene are associated with
- Legius syndrome.[2][3]
- Childhood leukemia[4]
Mutations
The following mutations have been observed:
- An exon 3 c.46C>T mutation leading to p.Arg16Stop.[4] 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)[5]
- 2 Frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp)[5]
- Missense (V44D)[5]
- p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.[6]
Disease Database
See also
- Neurofibromin 1
- Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations.[5]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: sprouty-related".
- ↑ Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E (November 2009). "Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome". JAMA 302 (19): 2111–8. doi:10.1001/jama.2009.1663. PMID 19920235. Lay summary – Medscape.
- ↑ "Legius Syndrome (SPRED1) Sequencing & (NF1) Sequencing Exon 22 (Exon 17)" (pdf). ARUP Laboratories. 2010. Retrieved 2011-06-07.
- ↑ 4.0 4.1 Pasmant E, Ballerini P, Lapillonne H, Perot C, Vidaud D, Leverger G, Landman-Parker J (July 2009). "SPRED1 disorder and predisposition to leukemia in children". Blood 114 (5): 1131. doi:10.1182/blood-2009-04-218503. PMID 19643996.
- ↑ 5.0 5.1 5.2 5.3 Spurlock G, Bennett E, Chuzhanova N, Thomas N, Jim HP, Side L, Davies S, Haan E, Kerr B, Huson SM, Upadhyaya M (July 2009). "SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype". J. Med. Genet. 46 (7): 431–7. doi:10.1136/jmg.2008.065474. PMID 19443465.
- ↑ Muram-Zborovski TM, Stevenson DA, Viskochil DH, Dries DC, Wilson AR, Rong Mao (October 2010). "SPRED 1 mutations in a neurofibromatosis clinic". J. Child Neurol. 25 (10): 1203–9. doi:10.1177/0883073809359540. PMC 3243064. PMID 20179001.
Further reading
- Batz C, Hasle H, Bergsträsser E et al. (2010). "Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?". Blood 115 (12): 2557–8. doi:10.1182/blood-2009-12-260901. PMID 20339110.
- Lock P, I ST, Straffon AF et al. (2006). "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination.". Biochem. Biophys. Res. Commun. 351 (4): 1018–23. doi:10.1016/j.bbrc.2006.10.150. PMID 17094949.
- Pasmant E, Sabbagh A, Hanna N et al. (2009). "SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.". J. Med. Genet. 46 (7): 425–30. doi:10.1136/jmg.2008.065243. PMID 19366998.
- Nonami A, Taketomi T, Kimura A et al. (2005). "The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1.". Genes Cells 10 (9): 887–95. doi:10.1111/j.1365-2443.2005.00886.x. PMID 16115197.
- Szafranski K, Schindler S, Taudien S et al. (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns.". Genome Biol. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
- Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Chandramouli S, Yu CY, Yusoff P et al. (2008). "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling.". J. Biol. Chem. 283 (3): 1679–91. doi:10.1074/jbc.M705457200. PMID 17974561.
- Johne C, Matenia D, Li XY et al. (2008). "Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton.". Mol. Biol. Cell 19 (4): 1391–403. doi:10.1091/mbc.E07-07-0730. PMC 2291396. PMID 18216281.
- Nonami A, Kato R, Taniguchi K et al. (2004). "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.". J. Biol. Chem. 279 (50): 52543–51. doi:10.1074/jbc.M405189200. PMID 15465815.
- Talmud PJ, Drenos F, Shah S et al. (2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.". Am. J. Hum. Genet. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
- Colland F, Jacq X, Trouplin V et al. (2004). "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
- Brems H, Chmara M, Sahbatou M et al. (2007). "Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype.". Nat. Genet. 39 (9): 1120–6. doi:10.1038/ng2113. PMID 17704776.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Yoshida T, Hisamoto T, Akiba J et al. (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 et al. (2005). "Distinct requirements for the Sprouty domain for functional activity of Spred proteins.". Biochem. J. 388 (Pt 2): 445–54. doi:10.1042/BJ20041284. PMC 1138951. PMID 15683364.
- Bailey SD, Xie C, Do R et al. (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.
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